Consumer medicine information

Cosentyx

Secukinumab

BRAND INFORMATION

Brand name

Cosentyx

Active ingredient

Secukinumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cosentyx.

SUMMARY CMI

COSENTYX®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I using COSENTYX?

COSENTYX contains the active ingredient secukinumab. COSENTYX is used to treat plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis and hidradenitis suppurativa.

For more information, see Section 1. Why am I using COSENTYX? in the full CMI.

2. What should I know before I use COSENTYX?

Do not use if you have ever had an allergic reaction to secukinumab or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use COSENTYX? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with COSENTYX and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use COSENTYX?

  • Your healthcare provider will prescribe the dose of COSENTYX that is right for you. Use COSENTYX exactly as prescribed.
  • Do not try to inject COSENTYX yourself until you or your caregiver has been shown how by your healthcare provider.
  • If you have forgotten to inject a dose of COSENTYX, do not take a double dose to make up for the dose you missed.

More instructions can be found in Section 4. How do I use COSENTYX? in the full CMI.

5. What should I know while using COSENTYX?

Things you should do
  • Discontinue treatment and tell your doctor or pharmacist immediately if you get any signs or symptoms of a potentially serious infection or an allergic reaction during treatment with COSENTYX.
  • Tell your doctor you are taking COSENTYX before a vaccination as live vaccines are not suitable for you.
  • Tell your doctor if you have ever had hepatitis B
Things you should not do
  • Do not stop taking your medicine or change dosage without checking with your doctor first.
  • Do not use this medicine if the liquid contains easily visible particles, is cloudy or is distinctly brown.
  • Do not use if the outer box or blister seals are broken, or if it has been dropped with the cap removed.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how COSENTYX affects you.
Looking after your medicine
  • Keep it in a refrigerator at 2°C to 8°C. Do not freeze it.
  • If necessary, COSENTYX can be left out of the refrigerator for a single period of up to 4 days at room temperature, not above 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

For more information, see Section 5. What should I know while using COSENTYX? in the full CMI.

6. Are there any side effects?

All medicines can have side effects although not everybody gets them. The most common side effects of COSENTYX include cold symptoms, diarrhea, and upper respiratory infections. COSENTYX may cause serious allergic reactions.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking COSENTYX.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring due to approval of an extension of indications. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.



FULL CMI

COSENTYX® (koe-sen-tix)

Active ingredient(s): secukinumab

Consumer Medicine Information (CMI)

This leaflet provides important information about using COSENTYX. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using COSENTYX.

Where to find information in this leaflet:

1. Why am I using COSENTYX?
2. What should I know before I use COSENTYX?
3. What if I am taking other medicines?
4. How do I use COSENTYX?
5. What should I know while using COSENTYX?
6. Are there any side effects?
7. Product details

1. Why am I using COSENTYX?

COSENTYX contains the active ingredient secukinumab. COSENTYX is a fully-human monoclonal antibody and belongs to a group of medicines called interleukin (IL) inhibitors. Monoclonal antibodies are proteins that recognise and attach specifically to certain proteins in the body. COSENTYX works by stopping the activity of the IL-17A protein which is present at increased levels in the following conditions:

  • Plaque psoriasis
  • Psoriatic arthritis
  • Axial spondyloarthritis, including ankylosing spondylitis (axial spondyloarthritis with radiographic damage) and non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic damage)
  • Juvenile idiopathic arthritis (JIA), including Enthesitis Related Arthritis (ERA) and Juvenile Psoriatic Arthritis (JPsA)
  • Hidradenitis suppurativa

Plaque psoriasis

COSENTYX is used to treat a skin condition called 'moderate to severe plaque psoriasis' in patients 6 years and older.

Plaque psoriasis causes inflammation of the skin.

Psoriatic arthritis

COSENTYX is used to treat a condition called 'psoriatic arthritis'. The condition is an inflammatory disease of the joints, often accompanied by psoriasis.

Axial spondyloarthritis, including ankylosing spondylitis (axial spondyloarthritis with radiographic damage) and non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic damage)

COSENTYX is used to treat a condition called 'ankylosing spondylitis' and 'non-radiographic axial spondyloarthritis' in adults. These conditions are inflammatory diseases primarily affecting the spine which causes inflammation of the spinal joints.

Juvenile idiopathic arthritis, including Enthesitis Related (ERA) and Juvenile Psoriatic Arthritis (JPsA)

These conditions are inflammatory diseases affecting the joints and the places where tendons join the bone. In JPsA patients 2 years and older and ERA patients 4 years and older, COSENTYX reduces the symptoms of these diseases and improves their ability to do normal daily activities.

In patients with plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis the body produces increased amounts of a protein called IL-17A. This may lead to symptoms such as itching, pain, scaling in psoriasis, swollen and tender joints in psoriatic arthritis, and pain in the spine in axial spondyloarthritis.

Hidradenitis suppurativa

COSENTYX is used to treat a condition called hidradenitis suppurativa, also sometimes called acne inversa or Verneuil's disease. This condition is a chronic and painful inflammatory skin disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and buttocks. Scarring may also occur in affected areas. COSENTYX can reduce the number of nodules and abscesses you have and may reduce the pain that is often associated with the disease.

COSENTYX is used in adults with hidradenitis suppurativa and can be used alone or with antibiotics.

2. What should I know before I use COSENTYX?

Warnings

Do not use COSENTYX if:

  • you are allergic to secukinumab, or any of the ingredients listed at the end of this leaflet.Always check the ingredients to make sure you can use this medicine. Some of the symptoms of an allergic reaction may include:
    - shortness of breath, wheezing or difficulty breathing or swallowing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin
    If you think you may be allergic, ask your doctor for advice before using COSENTYX.
  • Do not take COSENTYX if you have an active infection which your doctor thinks is important.
  • Do not take COSENTYX if there are visible signs of deterioration. If it has expired or is damaged, return it to your pharmacist for disposal.

Check with your doctor if you:

  • are not sure whether you should start taking this medicine
  • have tuberculosis
  • have ever had hepatitis B
  • have ever been diagnosed with inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  • had a recent vaccination or if you will receive a live vaccine during treatment with COSENTYX
  • ever had an allergic reaction to latex

Tell your doctor or pharmacist immediately if you get any of these symptoms during treatment with Cosentyx:

  • If you develop itchy rash, dry skin, dry patches, inflamed skin, coin-shaped spots on the skin [dermatitis (including eczema)].
  • If you develop severe inflammation of the entire skin surface (dermatitis exfoliative).

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. COSENTYX is not recommended during pregnancy unless the benefits clearly outweigh the potential risks.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Special populations

  • COSENTYX is not recommended for children under 6 years of age with plaque psoriasis because it has not been studied in this age group.
  • Cosentyx is not recommended for children under 4 years of age with Enthesitis Related Arthritis (ERA) and for children under 2 years of age with Juvenile Psoriatic Arthritis (JPsA) categories of Juvenile Idiopathic Arthritis (JIA) because it has not been studied in this age group.
  • COSENTYX is not recommended for children and adolescents (under 18 years of age) in other indications because it has not been studied in this age group.
  • COSENTYX may be used by people aged 65 years and over.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Tell your doctor or pharmacist if you:

  • are taking a blood thinning medicine called warfarin.
  • are taking, have recently taken or might take any other medicines.
  • have recently had or are going to have a vaccination.
    You should not receive certain types of vaccines (live vaccines) while using COSENTYX. It is recommended that children and adolescents receive all age-appropriate vaccines according to current guidelines before using COSENTYX.

Such medicines may interfere with COSENTYX and affect how it works. You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect COSENTYX. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

4. How do I use COSENTYX?

How much to give / use

Your doctor will decide how much COSENTYX you need.

  • Plaque psoriasis
    In adults, the recommended dose is 300 mg by subcutaneous injection with initial loading dose at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. If you weigh 90 kgs or higher, further adjustments to your dose may be recommended by your doctor. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
    In children 6 years and older, the recommended dose is based on body weight and is given by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month.
    For children receiving the 75mg dose, the 75mg/0.5mL pre-filled syringe should be used.
  • Psoriatic arthritis
    The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on your response, your doctor may increase the dose to 300 mg.
    For psoriatic arthritis patients who also have moderate to severe plaque psoriasis, your doctor may adjust the dose recommendation as needed.
    For patients who did not respond well to medicines called tumour necrosis factor (TNF), the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
    COSENTYX may be administered with or without methotrexate.
  • Axial Spondyloarthritis
    Ankylosing spondylitis
    The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on your response, your doctor may increase the dose to 300 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
    Non-radiographic axial spondyloarthritis
    With a loading dose: The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month.
    Without a loading dose: The recommended dose is 150 mg by subcutaneous injection every month.
  • Juvenile idiopathic arthritis
    Enthesitis Related Arthritis (ERA) in children 4 years and older
    The recommended dose is based on body weight and is given by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. For patients weighing < 50 kg the dose is 75 mg. For patients weighing ≥ 50 kg the dose is 150 mg.
    Juvenile Psoriatic Arthritis (JPsA) in children 2 years and older
    The recommended dose is based on body weight and is given by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. For patients weighing < 50 kg the dose is 75 mg. For patients weighing ≥ 50 kg the dose is 150 mg.
  • Hidradenitis Suppurativa
    The recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Further adjustments to your dose may be recommended by your doctor. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
  • Do not exceed the recommended dose.
  • Follow the instructions provided and use COSENTYX until your doctor tells you to stop.

How to give COSENTYX

Follow all directions given to you by your doctor, nurse or pharmacist carefully. They may differ from the information contained in this leaflet.

Always use COSENTYX as your doctor has told you. You should check with your doctor, nurse or pharmacist if you are not sure.

COSENTYX is intended for subcutaneous use. This means that it is injected into the fatty tissue just under the skin.

The injection may be given by your doctor or nurse or caregiver or you may be taught how to inject yourself with the medicine.

You and your doctor should decide if you should inject COSENTYX yourself.

After proper training in subcutaneous injection technique, patients ≥ 12 years old may self-inject COSENTYX or, for all patients ≥ 6 years old, the injection may be given by a caregiver if your doctor determines that it is appropriate.

It is important not to try to inject yourself until you have been trained by your doctor, nurse or pharmacist. A caregiver may also give you your COSENTYX injection after proper training.

If you do not understand the instructions on the label ask your doctor or pharmacist for help.

Choosing the injection sites

The injection sites are where the skin will be pierced to administer the subcutaneous injection.

The recommended site is the front of your thighs. You may also use the lower abdomen, but not the area five centimetres around the navel (belly button). Choose a different site each time you give yourself an injection.

If a caregiver is giving you the injection, the outer upper arms may also be used (Shown in grey in the diagram for illustrative purposes).

Do not inject into areas where the skin is tender, bruised, red, scaly or hard. Avoid areas with scars or stretch marks

Read the Instructions for Use on how to use COSENTYX all the way through before removing COSENTYX from the refrigerator. These instructions are to help you to inject correctly.

These instructions are also available via the following hyperlinks:

COSENTYX 75 mg/0.5 mL solution for injection in pre-filled syringe: medsinfo.com.au/media/nvicos7s

COSENTYX 150 mg/1 mL solution for injection in pre-filled pen: medsinfo.com.au/media/nvicos1p

COSENTYX 300 mg/2 mL solution for injection in pre-filled pen: medsinfo.com.au/media/nvicos3p

How long to use COSENTYX

This is a long-term treatment. Keep using this medicine for as long as your doctor tells you.

Your doctor will regularly monitor your condition to check that the treatment is having the desired effect.

If you forget to use COSENTYX

If you have forgotten to inject a dose of COSENTYX, inject the next dose as soon as you remember. Then talk to your doctor to discuss when you should inject the next dose.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to have your medicine, ask your pharmacist for some hints.

Do not take a double dose to make up for the dose you missed.

If you use too much COSENTYX

If you think that you have used too much COSENTYX, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using COSENTYX?

Things you should do

Discontinue treatment and tell your doctor or pharmacist immediately if you get any of these symptoms during treatment with COSENTYX.

Call your doctor straight away if you have:

  • Signs or symptoms of a potentially serious infection. These may include:
    - fever, flu-like symptoms, night sweats
    - feeling tired or short of breath; cough which will not go away
    - warm, red and painful skin, or a painful skin rash with blisters
    - burning when passing urine
  • Signs or symptoms of an allergic reaction. These may include:
    - difficulty breathing or swallowing
    - low blood pressure, which can cause dizziness or light-headedness
    - swelling of the face, lips, mouth or throat
    - severe itching of the skin, with a red rash or raised bumps
  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor will do tests from time to time to make sure the medicine is working and to prevent unwanted side effects. Your doctor will decide if and when you may restart the treatment.
  • If you need to be vaccinated, tell your doctor you are taking COSENTYX before you have the vaccination. Live vaccines will not be suitable for you.
  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking COSENTYX.
  • Remind any doctor, dentist or pharmacist you visit that you are using COSENTYX.

Things you should not do

  • Do not stop taking your medicine or change dosage without checking with your doctor first.
  • Never leave the prefilled pen lying around where others might tamper with it.
  • Do not open the sealed box until you are ready to use COSENTYX.
  • Do not use this medicine if the liquid contains easily visible particles, is cloudy or is distinctly brown.
  • Do not use the prefilled pen if either the seal on the outer box or the seal of the blister are broken. It may not be safe for you to use.
  • Do not shake the prefilled pen.
  • Do not use the pen if it has been dropped with the cap removed.
  • Do not take it to treat any other complaints unless your doctor tells you to.
  • Do not give this medicine to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how COSENTYX affects you.

No studies on the effects on the ability to drive and use of machines have been performed on COSENTYX.

Looking after your medicine

Keep it in a refrigerator at 2°C to 8°C. Do not freeze it.

Store it in the carton in order to protect it from light. Follow the instructions in the carton on how to take care of your medicine properly.

If necessary, COSENTYX can be left out of the refrigerator for a single period of up to 4 days at room temperature, not above 30°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

A locked section of the refrigerator, at least one-and-a-half metres above the ground, is a good place to store COSENTYX.

Keep it where young children cannot reach it.

When to discard your medicine

Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

Dispose of the used COSENTYX prefilled pens immediately after use in a sharps container. The COSENTYX prefilled pen should never be re-used.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects although not everybody gets them. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking COSENTYX.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • Infection and infestation related such as sore throat, stuffy nose, oral thrush, cold sores, infection of the external ear, discharge from the eye with itching, redness and swelling, and athlete's foot
  • Allergic reactions related such as runny nose, hives, headache, nausea, and itchy rash
  • Small, itchy blisters on the palms of hands, soles of feet and edges of the fingers and toes (dyshidrotic eczema)
  • inflammation of small blood vessels, which can lead to a skin rash with small red or purple bumps (vasculitis)
  • Diarrhoea
  • Painful period
  • Nausea, diarrhea, vomiting, abdominal pain and fever (symptoms of inflammatory bowel disease)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • Severe allergic reaction with shock (anaphylactic shock)
  • Signs of low levels of white blood cells such as fever, sore throat or mouth ulcers due to infections (neutropenia)
  • Symptoms of inflammatory bowel disease such as nausea, diarrhoea, vomiting, abdominal pain and fever. New cases of inflammatory bowel disease or "flare-ups" can happen with COSENTYX, and can sometimes be serious. If you have inflammatory bowel disease (ulcerative colitis or Crohn's disease), tell your doctor if you have worsening symptoms during treatment with COSENTYX or develop new symptoms of stomach pain or diarrhoea.
  • Severe inflammation of the entire skin surface (dermatitis exfoliative)
  • Itchy rash, dry skin, dry patches, inflamed skin, coin-shaped spots on the skin [dermatitis (including eczema)]
  • Swelling of the face, lips, tongue or throat (angioedema)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
  • The frequency of some side effects cannot be estimated from available data
    - Fungal infections of the skin and mucous membranes (thrush)
    - Inflammation of small blood vessels, which can lead to a skin rash with small red or purple bumps(hypersensitivity vasculitis)
    - Painful swelling and skin ulceration (pyoderma gangrenosum)
  • COSENTYX may affect the results of some blood tests, including:
    - slight increase in blood cholesterol and blood fat (triglycerides)
    - elevated liver enzymes
  • In clinical trials, major adverse cardiovascular events were rarely observed with COSENTYX.

Ask your doctor or pharmacist to answer any questions you may have. Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What COSENTYX contains

Active ingredientsecukinumab
Other ingredientstrehalose dihydrate
histidine / histidine hydrochloride monohydrate
methionine
polysorbate 80
water for injection
Potential allergensThis medicine does not contain sucrose, lactose, gluten, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What COSENTYX looks like

COSENTYX solution for injection is a clear liquid. Its colour may vary from colourless to slightly yellow.

COSENTYX 75 mg/0.5 mL solution for injection is available in packs containing 1 single-use pre-filled syringe (AUST R 353254).

COSENTYX 150 mg/1 mL solution for injection is available in packs containing 1 or 2 single-use pre-filled pens (AUST R 218800).

COSENTYX 300 mg/2 mL solution for injection is available in packs containing 1 single-use pre-filled pen (AUST R 353266).

Who distributes COSENTYX

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone 1 800 671 203

® = Registered Trademark

This leaflet was prepared in March 2025.

(cos050325c based on PI cos050325i)

Published by MIMS April 2025

BRAND INFORMATION

Brand name

Cosentyx

Active ingredient

Secukinumab

Schedule

S4

 

1 Name of Medicine

Secukinumab (rch).
Chemical name: recombinant human monoclonal anti-human interleukin-17A (IL-17A, IL-17) antibody of the IgG1/kappa isotype.

2 Qualitative and Quantitative Composition

Secukinumab is a recombinant fully human monoclonal antibody selective for interleukin-17A. Secukinumab is of the IgG1/κ-class produced in Chinese hamster ovary (CHO) cells.

3 Pharmaceutical Form

Powder for injection.

Each vial of powder for injection contains 150 mg of secukinumab as a lyophilised cake in glass vials.

Solution for injection.

Solution for injection in a single-use, 0.5 mL pre-filled syringe containing 75 mg secukinumab.
Solution for injection in a single-use, 1 mL pre-filled syringe and/or pen (auto-injector) containing 150 mg of secukinumab.
Solution for injection in a single-use, 2 mL pre-filled syringe and/or pen (auto-injector) containing 300 mg of secukinumab.

4 Clinical Particulars

4.1 Therapeutic Indications

Plaque psoriasis.

Cosentyx is indicated for the treatment of moderate to severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis.

Cosentyx is indicated for the treatment of adult patients with active psoriatic arthritis including axial manifestations of psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.

Axial spondyloarthritis (axSpA) with or without radiographic damage.

Ankylosing spondylitis (axSpA with radiographic damage).

Cosentyx is indicated for the treatment of adult patients with active ankylosing spondylitis.

Non-radiographic axial spondyloarthritis (axSpA without radiographic damage).

Cosentyx is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or MRI change, who have had an inadequate response to, or are intolerant to, NSAIDs.

Juvenile idiopathic arthritis (JIA).

Enthesitis-related arthritis (ERA).

Cosentyx is indicated for the treatment of active enthesitis-related arthritis in patients 4 years and older who have had an inadequate response or were intolerant to at least one NSAID and at least one DMARD.

Juvenile psoriatic arthritis (JPsA).

Cosentyx is indicated for the treatment of active juvenile psoriatic arthritis in patients 2 years and older who have had an inadequate response or were intolerant to at least one NSAID and at least one DMARD.

Hidradenitis suppurativa (HS).

Cosentyx is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adult patients with an inadequate response to conventional systemic hidradenitis suppurativa therapy.

4.2 Dose and Method of Administration

Dosage.

Plaque psoriasis.

Adult patients.

The recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Some patients ≥ 90 kgs may derive an additional benefit from receiving 300 mg every 2 weeks. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.

Paediatric patients.

The recommended dose is based on body weight (Table 1) and administered by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 75 mg dose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
Psoriatic arthritis. The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on clinical response, the dose can be increased to 300 mg.
For patients with concomitant moderate to severe plaque psoriasis, please refer to adult plaque psoriasis recommendation.
For patients who are anti-TNF-alpha inadequate responders (IR), the recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
Cosentyx may be administered with or without methotrexate.
Axial spondyloarthritis. Ankylosing spondylitis. The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on clinical response, the dose can be increased to 300 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.
Non-radiographic axial spondyloarthritis.

With a loading dose.

The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month.

Without a loading dose.

The recommended dose is 150 mg by subcutaneous injection every month.
Juvenile idiopathic arthritis (JIA).

Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA).

Cosentyx should be prescribed by specialist physicians experienced in the management of these conditions. The recommended dose is based on body weight. For patients weighing < 50 kg the dose is 75 mg. For patients weighing ≥ 50 kg the dose is 150 mg. Cosentyx is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month (every 4 weeks). Each 75 mg dose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg.
Available data suggest that a clinical response in JIA is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients not responding within this time period.
Hidradenitis suppurativa. The recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by a maintenance dose of 300 mg every 4 weeks. Some patients may derive an additional benefit from receiving 300 mg every 2 weeks. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.

Assessment prior to initiation of Cosentyx.

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Cosentyx (see Section 4.4 Special Warnings and Precautions for Use).

Special populations.

Patients with renal or hepatic impairment.

Cosentyx has not been specifically studied in these patient populations. No dose recommendations can be made.

Paediatric and adolescent patients.

Safety and effectiveness in paediatric patients with plaque psoriasis below the age of 6 years have not yet been established.
Safety and effectiveness in paediatric patients with the JIA category of ERA below the age of 4 years have not been established. Safety and effectiveness in paediatric patients with the JIA category of JPsA below the age of 2 years have not been established. Safety and effectiveness in paediatric patients with other categories of JIA have not been established.
Safety and effectiveness in patients below the age of 18 years in other indications have not yet been established.

Elderly patients (≥ 65 years of age).

No dose adjustment is needed for elderly patients.

Administration.

The product is for single use in one patient only. Discard any residue.

Powder for injection.

Cosentyx is administered by subcutaneous injection. Each vial of Cosentyx must be reconstituted with 1 mL of sterile water for injections to obtain a 150 mg/mL solution. The powder for injection should be administered by healthcare professionals only.

Pre-filled syringe and pre-filled pen.

Cosentyx is administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites.
Before injection, secukinumab may be allowed to reach room temperature (20 minutes) without removing the needle cap during this time.
Prior to administration, the liquid must be checked whether it is clear and colourless. The solution should not be used if discoloured, or cloudy, or if foreign particles are present.
After proper training in subcutaneous injection technique, patients ≥ 12 years old may self-inject Cosentyx or, for all patients ≥ 6 years old, the injection may be given by a caregiver if a physician determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients. Patients and/or caregivers should be instructed to inject the full amount of Cosentyx according to the instructions provided in the package leaflet. Comprehensive instructions for administration are given in the package leaflet.

Pre-filled syringe.

For patients receiving the 75 mg dose, the 75 mg/0.5 mL pre-filled syringe should be used. The intended injection sites for the 75 mg/0.5 mL pre-filled syringe are lower abdomen and front of the thighs (excluding the area 5 centimetres around the navel) or the upper outer arms if a caregiver is giving the injection, and the needle should be inserted at 45 degrees to the skin.
The intended injection sites for the 150 mg/1 mL and 300 mg/2 mL pre-filled syringe are front of the thighs or lower abdomen (excluding the area 5 centimetres around the navel) or the outer upper arms if a caregiver is giving the injection, and the needle should be inserted at a 45 degree angle to the skin.

Pre-filled pen.

The intended injection sites for the 150 mg/1 mL and 300 mg/2 mL pre-filled pen are front of the thighs or lower abdomen (excluding the area 5 centimetres around the navel) or the outer upper arms if a caregiver is giving the injection, and the needle should be inserted at a 90 degree angle to the skin.

4.3 Contraindications

Severe hypersensitivity reactions to the active substance or to any of the excipients (see Section 6.1 List of Excipients; Section 4.8 Adverse Effects (Undesirable Effects)).
Clinically important, active infections (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Infections.

Cosentyx has the potential to increase the risk of infections. In clinical studies, infections have been observed in patients receiving Cosentyx (see Section 4.8 Adverse Effects (Undesirable Effects)). Most of these were mild or moderate.
Related to the mechanism of action of Cosentyx, non-serious mucocutaneous candida infections were more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per 100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (see Section 4.8 Adverse Effects (Undesirable Effects)).
A similar increase in risk of infection was seen in placebo controlled trials in patients with psoriatic arthritis and axial spondyloarthritis. The incidence of some types of infections appeared to be dose dependent in clinical studies (see Section 4.8 Adverse Effects (Undesirable Effects)).
Caution should be exercised when considering the use of Cosentyx in patients with a chronic infection or a history of recurrent infection.
Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and Cosentyx should not be administered until the infection resolves.

Pre-treatment evaluation for tuberculosis.

Tuberculosis (active and/or latent reactivation) can occur in patients treated with Cosentyx. Patients should be evaluated for tuberculosis infection prior to initiating treatment with Cosentyx. Cosentyx should not be given to patients with active tuberculosis. Initiation of treatment for latent tuberculosis should be considered prior to administering Cosentyx. Anti-tuberculosis therapy should be considered prior to initiation of Cosentyx in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Patients should be closely monitored for signs and symptoms of active tuberculosis during and after treatment.

Hepatitis B reactivation.

Hepatitis B virus reactivation can occur in patients treated with Cosentyx. In accordance with clinical guidelines for immunosuppressants, testing patients for HBV infection is to be considered before initiating treatment with Cosentyx. Cosentyx should not be given to patients with active hepatitis B. Patients with evidence of positive HBV serology should be monitored for clinical and laboratory signs of HBV reactivation during Cosentyx treatment. If reactivation of HBV occurs while on Cosentyx, discontinuation of the treatment should be considered, and patients should be treated according to clinical guidelines.

Crohn's disease.

Caution should be exercised, when prescribing Cosentyx to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in Cosentyx treated patients during clinical trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with Cosentyx and have been reported with post-marketing use.
Patients who are treated with Cosentyx should be monitored for signs and symptoms of inflammatory bowel disease.

Hypersensitivity reactions.

In clinical studies, rare cases of anaphylactic reactions and angioedema have been observed in patients receiving Cosentyx. Angioedema cases have also been reported in the post-marketing setting. If an anaphylactic or other serious allergic reaction occurs, administration of Cosentyx should be discontinued immediately and appropriate therapy initiated.

Eczematous eruptions.

In post-marketing reports, cases of severe eczematous eruptions, including dermatitis-like eruptions, dyshidrotic eczema, and erythroderma (exfoliative dermatitis), were reported in patients receiving Cosentyx; some cases resulted in hospitalization (see Section 4.8 Adverse Effects (Undesirable Effects)). The onset of eczematous eruptions was variable, ranging from days to months after the first dose of Cosentyx.
Treatment with Cosentyx may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing Cosentyx.

Latex-sensitive individuals - 1 mL pre-filled syringe/pen and 0.5 mL pre-filled syringe only.

The removable caps of the Cosentyx 1 mL pre-filled syringe/pen and 0.5 mL pre-filled syringe contains a derivative of natural rubber latex. Although no natural rubber latex is detected in the cap, the safe use of Cosentyx pre-filled syringe/pen in latex sensitive individuals has not been studied.

Vaccinations.

Live vaccines should not be given concurrently with Cosentyx (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients treated with Cosentyx may receive vaccinations, except for live vaccines. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of Cosentyx-treated and placebo-treated patients were able to mount an adequate immune response of at least a 4-fold increase in antibody titres to meningococcal or influenza vaccines. The data suggest that Cosentyx does not suppress the humoral immune response to the meningococcal and influenza vaccines.
Patients receiving Cosentyx may receive concurrent inactivated or non-live vaccinations.
Prior to initiating therapy with Cosentyx, it is recommended that paediatric patients receive all age-appropriate immunisations as per current immunisation guidelines.

Use in hepatic impairment.

No data are available in patients with hepatic impairment.

Use in renal impairment.

No data are available in patients with renal impairment.

Use in the elderly.

Based on population PK analysis, clearance in patients aged 65 and older (n = 230) and patients less than 65 years of age was similar.

Paediatric use.

Safety and effectiveness in paediatric patients with plaque psoriasis below the age of 6 years have not yet been established.
Data on effectiveness and safety in paediatric patients younger than 6 years old with active JIA were derived by applying population pharmacokinetic analyses updating a previously established model in adults with psoriasis, psoriatic arthritis or axial spondyloarthropathy, and children with psoriasis. Three children with JIA contributing data to the analysis were younger than 6 years old.
Children were enrolled into the JIA study according to the following inclusion criteria:

Modified JPsA.

Children with arthritis and psoriasis;
children with arthritis with two or more of (a) dactylitis, (b) nail pitting or onycholysis, (c) psoriasis in a first degree relative;
HLA-B27 positive males with arthritis beginning after the sixth birthday were not excluded;
children with a diagnosis of ankylosing spondylitis, sacroiliitis with inflammatory bowel disease, reactive arthritis, acute anterior uveitis, or a history of one of these disorders in a first-degree relative were not excluded.

ERA.

Children with arthritis and enthesitis;
children with arthritis or enthesitis with two or more of (a) presence or history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain, (b) HLA-B27 positivity, (c) acute (symptomatic) anterior uveitis, (d) history of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis or acute anterior uveitis in a first-degree relative, (e) onset of arthritis in a boy over the age of six years.
Children with IgM RF on at least two occasions more than three months apart or with systemic JIA were excluded from the study.
Safety and effectiveness in patients below the age of 18 years in other indications have not yet been established.

Effects on laboratory tests.

There is no known interference between Cosentyx and routine laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Live vaccines should not be given concurrently with Cosentyx (also see Section 4.4 Special Warnings and Precautions for Use).
In a study in adult subjects with plaque psoriasis, no clinically relevant pharmacokinetic interaction was observed between secukinumab and midazolam (CYP3A4 substrate). Following initiation or discontinuation and during ongoing use of secukinumab in patients being treated with CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed.
No interaction was seen when Cosentyx was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and axial spondyloarthritis).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no special recommendations for females of reproductive potential.
The effect of Cosentyx on human fertility has not been evaluated.
Fertility was unaffected in mice treated with an anti-murine IL17-A antibody.
(Category C)
There are no adequate data from the use of Cosentyx in pregnant women. Secukinumab was shown to cross the placenta in monkeys. Use of secukinumab during pregnancy may compromise the immunity of the fetus and neonate.
In an embryofetal development study in cynomolgus monkeys, secukinumab showed no maternal toxicity, embryofetal toxicity or teratogenicity when administered throughout organogenesis and late gestation at up to 150 mg/kg/week.
Cosentyx should be used in pregnancy only if the benefits clearly outweigh the potential risks.
If secukinumab has been used during pregnancy, administration of live vaccines to newborns/ infants for 16 weeks after the mother's last dose of secukinumab is generally not recommended.
 It is not known whether secukinumab is excreted in human milk. Because immunoglobulins are excreted in human milk, caution should be exercised when Cosentyx is administered to a woman who is breastfeeding and a decision on whether to discontinue breastfeeding during treatment should be made.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use of machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

Summary of the safety profile.

Over 20,000 patients have been treated with Cosentyx in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 34,908 patient years of exposure. Of these, over 14,000 patients were exposed to Cosentyx for at least one year.

Adverse reactions in plaque psoriasis.

Four placebo controlled phase III studies in plaque psoriasis were pooled to evaluate the safety of Cosentyx in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,076 patients were evaluated (692 patients on 150 mg, 690 patients on 300 mg and 694 patients on placebo).
The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis, rhinitis). Most of the events were mild or moderate in severity.
In the placebo-controlled period of plaque psoriasis phase III studies the proportion of patients who discontinued treatment due to adverse events was approximately 1.2% in the Cosentyx arm and 1.2% in the placebo arm. The adverse reactions from clinical studies (Table 2 and Table 3) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000).
Adverse reactions that occurred at less than 1% frequency in the placebo controlled period of the ERASURE, FIXTURE, FEATURE and JUNCTURE studies through week 12 are given in Table 4.

Paediatric patients.

The safety of Cosentyx was assessed in two 52 week phase III studies in paediatric patients from 6 to less than 18 years of age: 162 patients with severe plaque psoriasis. 84 patients with moderate to severe plaque psoriasis. The distribution of patients across age and weight is presented in Table 11, see Section 5.1. The safety profile reported in these studies was consistent with the safety profile reported in adult plaque psoriasis patients. Neutrophil counts are generally lower in children and adolescents than in adults with or without treatment. The variations seen in the paediatric clinical trials with Cosentyx were not clinically significant. See Tables 5 and 6.

Adverse drug reactions from spontaneous reports and literature cases (frequency not known).

The following adverse drug reactions have been derived from post-marketing experience with Cosentyx via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. See Table 7.

Description of selected adverse drug reactions.

Adult patients.

Infections.

In the placebo controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with Cosentyx and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28.7% of patients treated with Cosentyx compared with 18.9% of patients treated with placebo. Most of these were mild or moderate. Serious infections occurred in 0.14% of patients treated with Cosentyx and in 0.3% of patients treated with placebo (see Section 4.4 Special Warnings and Precautions for Use).
Over the entire treatment period (a total of 3,430 patients treated with Cosentyx for up to 52 weeks for the majority of patients), infections were reported in 47.5% of patients treated with Cosentyx (0.9 per patient year of follow-up). Serious infections were reported in 1.2% of patients treated with Cosentyx (0.015 per patient year of follow-up).
There was an increase in mucosal or cutaneous candidiasis, related to the mechanism of action. The cases were mild or moderate in severity, non-serious, responsive to standard treatment and did not necessitate treatment discontinuation. Frequency of candida infection was 1.2% (secukinumab 300 mg) vs 0.3% (placebo and etanercept arms) in the induction period.
Infection rates as observed in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) clinical studies were similar to what was observed in the psoriasis studies.
Patients with hidradenitis suppurativa are more susceptible to infections. In the placebo-controlled period of clinical studies in hidradenitis suppurativa (a total of 721 patients treated with secukinumab and 363 patients treated with placebo for up to 16 weeks), infections were numerically higher to those observed in the psoriasis studies (30.8% of patients treated with secukinumab compared with 31.7% in patients treated with placebo). Most of these were non-serious, mild or moderate in severity and did not require treatment discontinuation or interruption.

Neutropenia.

In psoriasis phase 3 clinical studies, neutropenia was more frequently observed with secukinumab than with placebo, but most cases were mild, transient and reversible. Neutropenia < 1.0-0.5 x 109/L (CTCAE Grade 3) was reported in 18 out of 3,430 (0.5%) patients on secukinumab, with no dose dependence and no temporal relationship to infections in 15 out of 18 cases. There were no reported cases of more severe neutropenia. Non-serious infections with usual response to standard care and not requiring discontinuation of Cosentyx were reported in the remaining 3 cases.
In the paediatric safety pool, which includes all subjects who took at least one dose of Cosentyx during the treatment periods [198 subjects (287 patient years)], 22 (11%) subjects reported ≥ CTCAE Grade 2 neutropenia (≥ 1,000 to < 1,500 cells/mm3) with 57% of subjects followed for one year or more and 30% of subjects followed for two years or more. During the placebo-controlled period which included a total of 80 subjects treated with secukinumab and 41 subjects treated with placebo up to 12 weeks, ≥ CTCAE Grade 2 neutropenia was reported in 3 (4%) of the subjects treated with secukinumab compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia.
The frequency of neutropenia in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) is similar to psoriasis.
Rare cases of neutropenia < 0.5 x 109/L (CTCAE Grade 4) were reported.

Hypersensitivity reactions.

In clinical studies, urticaria, rare case of anaphylactic reaction and angioedema were observed in patients receiving Cosentyx. Angioedema cases have also been reported in the post-marketing setting.

Immunogenicity.

In psoriasis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), and hidradenitis suppurativa clinical studies less than 1% of patients treated with Cosentyx developed antibodies to secukinumab up to 52 weeks of treatment. About half of the treatment emergent anti-drug antibodies were neutralising, but this was not associated with loss of efficacy or PK abnormalities.

Reproductive system related adverse events.

In the induction period of psoriasis clinical studies, mild and moderate reproductive system adverse events were reported in females, including: dysmenorrhoea (secukinumab 300 mg, 1.9%; placebo, 0.5%; etanercept, 1.1%), menorrhagia (secukinumab 300 mg, 0.9%; placebo, 0%; etanercept, 0%) and metrorrhagia (including menometrorrhagia) (secukinumab 300 mg, 1.4%; placebo, 0%; etanercept, 0%). Women of child-bearing potential were included in studies only if using adequate contraception.

Major adverse cardiovascular events (MACE).

In the secukinumab clinical trials, MACE events were observed in patients receiving secukinumab. In the phase 3 studies in psoriasis, PsA and AS, the exposure adjusted incidence rates of adjudication confirmed MACE cases per 100 patient years was 0.49 (19/3911.6 patient years, 95% CI 0.29, 0.76) for secukinumab versus 0.00 (0/351.3 patient years, 95% CI 0.00, 1.05) for placebo. In the Phase 3 study in nr-axSpA, the exposure adjusted incidence rates of adjudicated confirmed MACE cases per 100 patient-years was 0 (0/759.9 patient-years, 95% CI 0.0, 0.5) for secukinumab versus 1.0 (1/108.6 patient-years, 95% CI 0.0, 5.1). In the overall secukinumab program, the exposure adjusted incidence rates of adjudication confirmed cases per 100 patient years for secukinumab was 0.40 (25/6259.8 patient years, 95% CI 0.26, 0.59) versus 0.39 (2/515.1 patient years, 95% CI 0.05, 1.40) for placebo.

Adverse reactions in psoriatic arthritis.

Cosentyx was studied in five placebo-controlled psoriatic arthritis trials with 2,754 patients (1,871 patients on Cosentyx and 883 patients on placebo) with a total exposure of 4,478 patient-years of study exposure on Cosentyx. The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the Cosentyx groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, urinary tract infection, and hypercholesterolemia. The safety profile observed in patients with psoriatic arthritis treated with Cosentyx is consistent with the safety profile in psoriasis.
The proportion of patients with infections in the Cosentyx groups (28.5%) is similar to the placebo group (28.1%) (see Section 4.4 Special Warnings and Precautions for Use).
There were cases of Crohn's disease and ulcerative colitis that include patients who experienced either exacerbations or the development of new disease. In the psoriatic arthritis program with 2,536 patients exposed to Cosentyx there were 17 cases of inflammatory bowel disease during the entire treatment period (0.4 per 100 patient-years). During the placebo-controlled period 16 week period, there were seven cases of inflammatory bowel disease, of which five patients received secukinumab and two received placebo (see Section 4.4 Special Warnings and Precautions for Use).

Cholesterol and triglycerides.

CTCAE grade 1 and grade 2 elevations of blood cholesterol and triglyceride levels were reported in patients receiving secukinumab compared to placebo in psoriatic arthritis clinical trials.
The elevations of cholesterol levels were limited primarily to CTCAE grade 1 (28.7% vs. 19.1%, respectively) and grade 2 (1.6% vs. 0.5%, respectively). No cases of CTCAE grade 3 and grade 4 cholesterol levels were observed in either secukinumab or placebo groups during the placebo controlled period.
An increase in blood triglycerides levels was also observed in psoriatic arthritic patients receiving secukinumab compared to placebo (CTCAE Grade 1: 26.7% vs. 19.1%, Grade 2: 4.6% vs. 3.5%, Grade 3: 1.0% vs. 0.7% and Grade 4: 0.2% vs. 0.1%, respectively) up to Week 16.
Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol and triglycerides were also observed during long-term treatment with secukinumab.

Hepatic transaminases.

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was observed in psoriatic arthritis patients treated with secukinumab compared to placebo. The elevations in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 17.1% vs 14.8%; AST: 12.5% vs. 10.1%, respectively). No difference in the incidence of elevated ALT and AST was seen between secukinumab and placebo in CTCAE Grade 2, Grade 3 and Grade 4. No cases of CTCAE Grade 4 were observed for AST.
Elevations (mainly CTCAE Grade 1 and Grade 2) in ALT and AST was also observed during the long-term treatment with secukinumab.

Adverse reactions in axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis).

Cosentyx was studied in three placebo-controlled ankylosing spondylitis trials with 816 patients (544 patients on Cosentyx and 272 patients on placebo). The median duration of exposure for secukinumab-treated patients was 469 days in AS1 study, 460 days in AS2 study, and 1,142 days in AS3 study. During the 16-week placebo-controlled period of the trials in patients with ankylosing spondylitis, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (60% and 55%, respectively).
The overall safety profile of Cosentyx in AS3 study remained in line with the safety profile established in the pivotal AS1 and AS2 studies, which are summarised in the next paragraphs.
The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the Cosentyx groups than the placebo groups during the 16 week placebo controlled period were nasopharyngitis, nausea, and upper respiratory tract infection.
Cosentyx was also studied in one placebo-controlled non-radiographic axial spondyloarthritis trial with 555 patients (369 patients on Cosentyx and 186 patients on placebo) for a total of 757.9 patient-years of study exposure (median duration of exposure for secukinumab-treated patients: 540 days).
During the 20-week placebo-controlled period of the trial in patients with non-radiographic axial spondyloarthritis, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (61.2% and 54.3%, respectively). The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the Cosentyx groups than the placebo group during the 20-week placebo-controlled period were nasopharyngitis, diarrhoea, headache, upper respiratory tract infection, oropharyngeal pain, back pain, nausea, urinary tract infection, abdominal pain upper and tonsillitis.
The safety profile observed in patients with axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) treated with Cosentyx is consistent with the safety profile in psoriasis.
Similar to clinical trials in patients with psoriasis, there was an increased proportion of ankylosing spondylitis patients with infections in the Cosentyx groups (31%) compared to the placebo group (18%). The proportion of non-radiographic axial spondyloarthritis patients with infections is similar in the Cosentyx groups (35.5%) compared to the placebo group (32.8%) (see Section 4.4 Special Warnings and Precautions for Use).
In the ankylosing spondylitis program, with 571 patients exposed to Cosentyx there were 8 cases of inflammatory bowel disease during the entire treatment period (5 Crohn's (0.7 per 100 patient years) and 3 ulcerative colitis (0.4 per 100 patient years)). During the placebo controlled 16 week period, there were 2 Crohn's disease exacerbations and 1 new onset ulcerative colitis case that was a serious adverse event in patients treated with Cosentyx compared to none of the patients treated with placebo. During the remainder of the study when all patients received Cosentyx, 1 patient developed Crohn's disease, 2 patients had Crohn's exacerbations, 1 patient developed ulcerative colitis, and 1 patient had an ulcerative colitis exacerbation. In the non-radiographic axial spondyloarthritis program, with 524 patients exposed to Cosentyx, there were 7 cases of inflammatory bowel disease during the entire treatment period (5 Crohn's (0.7 per 100 patient-years) and 2 ulcerative colitis (0.3 per 100 patient-years)). During the placebo-controlled 20-week period, there was 1 new onset of Crohn's disease in a patient treated with Cosentyx compared to none of the patients treated with placebo. During the remainder of the study when all patients received Cosentyx, 3 patients developed Crohn's disease, 1 patient had Crohn's disease exacerbations, 1 patient developed ulcerative colitis, and 1 patient had an ulcerative colitis exacerbation (see Section 4.4 Special Warnings and Precautions for Use).

Cholesterol and triglycerides.

CTCAE Grade 1 and Grade 2 elevations of blood cholesterol and triglyceride levels were reported in patients receiving secukinumab compared to placebo in ankylosing spondylitis clinical trials.
The elevations of cholesterol levels were limited primarily to CTCAE Grade 1 (20.0% vs. 19.8%, respectively). Increase in CTCAE Grade 2 cholesterol levels was uncommon (0.8% vs. 0.0%, respectively) and no cases of CTCAE Grade 3 and Grade 4 cholesterol levels were observed in both secukinumab and placebo groups during the placebo controlled period.
An increase in blood triglycerides levels was also observed in ankylosing spondylitis patients receiving secukinumab or placebo (CTCAE Grade 1: 17.8% vs. 17.1%, Grade 2: 2.7% vs. 2.7%, and Grade 3: 0.8% vs. 0.5%, respectively). No cases of CTCAE Grade 4 triglyceride levels were reported during the placebo controlled period.
Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol and triglycerides were also observed during long-term treatment with secukinumab.
CTCAE Grade 1 and Grade 2 elevations of blood cholesterol and triglyceride levels were also reported in patients receiving secukinumab compared to placebo in the non-radiographic axial spondyloarthritis clinical trial.
An increase in cholesterol levels was observed in non-radiographic axial spondyloarthritis patients receiving secukinumab or placebo (CTCAE Grade 1: 16.2% vs. 15.8%, Grade 2: 0.8% vs. 0.6%, and Grade 3: 0.3% vs. 0.0%, respectively). No cases of CTCAE Grade 4 cholesterol levels were reported during the placebo-controlled period.
An increase in blood triglycerides levels was also observed in non-radiographic axial spondyloarthritis patients receiving secukinumab or placebo (CTCAE Grade 1: 18.0% vs. 21.0%, Grade 2: 3.2% vs. 3.4%, and Grade 3: 0.6% vs. 0.5%, respectively). No cases of CTCAE Grade 4 triglyceride levels were reported during the placebo-controlled period.
Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol and triglycerides were also observed during long-term treatment with secukinumab.

Hepatic transaminases.

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was observed in ankylosing spondylitis patients treated with secukinumab compared to placebo. The elevations in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 16.6% vs. 7.1%; AST: 11.3% vs. 7.0%, respectively). Increase in CTCAE Grade 2 and Grade 3 hepatic transaminase levels was uncommon in both secukinumab and placebo groups (Grade 2 ALT: 1.0% vs. 0.5%, AST: 0.5% vs. 0.0%; Grade 3 ALT: 0.8% vs. 0.0%, AST: 0.8% vs. 1.6%, respectively). One case of CTCAE Grade 4 ALT levels was reported in the placebo group and no cases of CTCAE Grade 4 ALT and AST levels were reported in the secukinumab group.
Elevations (mainly CTCAE Grade 1 and Grade 2) in ALT and AST was also observed during the long-term treatment with secukinumab.
During the placebo-controlled period, increased incidence of elevated hepatic transaminases was observed in non-radiographic axial spondyloarthritis patients treated with secukinumab compared to placebo. The elevations in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 12.9% vs 9.5%; AST: 11.1% vs. 2.8%, respectively). Increase in CTCAE Grade 2 and Grade 3 hepatic transaminase levels was uncommon in both secukinumab and placebo groups (Grade 2 ALT: 1.1% vs. 0.5%, AST: 0.5% vs. 0.0%; Grade 3 ALT: 0.0% vs. 0.0%, AST: 0.3% vs. 0.5%, respectively). No cases of CTCAE Grade 4 ALT and AST levels were reported during the placebo-controlled period.
Elevations (mainly CTCAE Grade 1 and Grade 2) in ALT and AST was also observed during the long-term treatment with secukinumab.

Adverse reactions in juvenile idiopathic arthritis (JIA) (enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA)).

The safety of Cosentyx was also assessed in a Phase III study in 86 paediatric patients from 2 to less than 18 years of age with the ERA and JPsA categories of JIA. Three children were aged younger than 6 years. The safety profile reported in this study was consistent with the safety profile reported in adult patients.

Adverse reactions in hidradenitis suppurativa.

Cosentyx was studied in two placebo-controlled hidradenitis suppurativa trials with 1,084 patients (721 patients on Cosentyx and 363 on placebo) with a total exposure of 825 patient years of study exposure (median duration of exposure for secukinumab-treated patients: 307 days, time on placebo 112 days).
The safety profile observed in trial patients with HS treated with Cosentyx was consistent with the known trial safety profile observed in psoriasis.

4.9 Overdose

No case of overdose has been reported in clinical studies.
Doses up to 30 mg/kg (i.e. approximately 2,000 mg to 3,000 mg) have been administered intravenously in clinical studies without dose-limiting toxicity.
In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: interleukin inhibitors; ATC Code: L04AC10.

5.1 Pharmacodynamic Properties

Serum levels of total IL-17A (free and secukinumab bound IL-17A) are increased due to reduced clearance of secukinumab bound IL-17A within 2 to 7 days in patients receiving secukinumab, indicating that secukinumab selectively captures free IL-17A which plays a key role in the pathogenesis of plaque psoriasis.
In a study with secukinumab, infiltrating epidermal neutrophils and various neutrophil associated markers that are increased in lesional skin of plaque psoriasis patients were significantly reduced after one to two weeks of treatment.
Secukinumab has been shown to lower (within 1 to 2 weeks of treatment) levels of C-reactive protein, which is a marker of inflammation in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis).

Mechanism of action.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A). IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, hidradenitis suppurativa, psoriatic arthritis, and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Increased numbers of IL-17A producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the blood of patients with plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis and affected skin of patients with plaque psoriasis. IL-17A is highly up-regulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients. Higher frequency of IL-17 producing cells was detected in the synovial fluid of patients with psoriatic arthritis and in the subchondral bone marrow of facet joints from patients with axial spondyloarthritis. IL-17A is considerably upregulated in hidradenitis suppurativa lesions compared to psoriasis patients and healthy controls, and significantly increased IL-17A serum levels have been observed in affected patients. Inhibition of IL-17A was shown to be effective in the treatment of AS, thus establishing the key role of this cytokine in axial spondyloarthritis (see Clinical trials).
IL-17A also promotes tissue inflammation, neutrophil infiltration, bone and tissue destruction, and tissue remodelling including angiogenesis and fibrosis.
Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A mediated contributions to autoimmune and inflammatory diseases. Clinically relevant levels of secukinumab reach the skin and reduce local inflammatory markers. As a direct consequence, treatment with secukinumab reduces erythema, induration, and desquamation present in plaque psoriasis lesions.

Clinical trials.

Plaque psoriasis. Adult patients. The safety and efficacy of Cosentyx were evaluated versus placebo or etanercept in four randomised, double blind, placebo controlled phase 3 studies in adult patients with moderate to severe chronic plaque type psoriasis poorly controlled by topical treatments and/or phototherapy and/or previous systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE). The safety and efficacy of Cosentyx were evaluated versus placebo or etanercept in four randomised, double blind, placebo controlled phase 3 studies in patients with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE). In addition, one study assessed a chronic treatment regimen versus a 'retreatment as needed' regimen (SCULPTURE). In these studies, each 300 mg dose was given as two subcutaneous injections of 150 mg. The co-primary endpoints in the placebo and active controlled studies were the proportion of patients who achieved a PASI 75 response and IGA mod 2011 'clear' or 'almost clear' response versus placebo at Week 12.
Key exclusion criteria across pivotal trials were: forms of psoriasis other than chronic plaque type; drug induced psoriasis; ongoing use of certain psoriasis treatments, e.g. topical or systemic corticosteroids or UV therapy; patients with active, ongoing inflammatory disease; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA class III and IV); patients with serum creatinine > 176.8 micromol/L or with white blood cell count < 2,500/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of child-bearing potential not using effective contraception during the study.
Of the 2,403 patients who were included in the placebo-controlled studies, 79% were biological medicine-naïve, 45% failed treatment with non-biological medicines, 8% failed treatment with biological medicines, 6% were anti-TNF failures, and 2% were anti-p40 failures. Baseline disease characteristics were generally consistent across all treatment groups with a median baseline Psoriasis Area Severity Index (PASI) score from 19 to 20, IGA mod 2011 baseline score ranged from "moderate" (62%) to "severe" (38%), median baseline Body Surface Area (BSA) ≥ 27 and median Dermatology Life Quality Index (DLQI) score from 10 to 12. Approximately 15 to 25% of patients in phase III studies had psoriatic arthritis (PsA) at baseline.

ERASURE study (A2302).

This trial evaluated 738 patients. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were randomised to receive placebo who were non-responders at week 12 were then crossed over to receive Cosentyx (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15, followed by the same dose every month starting at week 16. All patients were followed for up to 52 weeks following first administration of study treatment.

FIXTURE study (A2303).

This trial evaluated 1,306 patients. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were randomised to etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg every week. Patients were randomised to receive placebo who were non-responders at week 12 then crossed over to receive Cosentyx (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15, followed by the same dose every month starting at week 16. All patients were followed for up to 52 weeks following first administration of study treatment.

FEATURE study (A2308).

This trial evaluated 177 patients using a pre-filled syringe compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Cosentyx self administration via the pre-filled syringe. Patients randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were also randomised to receive placebo at weeks 0, 1, 2, 3, and 4 followed by the same dose every month.

JUNCTURE study (A2309).

This trial evaluated 182 patients using a pre-filled pen compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Cosentyx self administration via the pre-filled pen. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4. Patients were also randomised to receive placebo at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4.

SCULPTURE study (A2304).

This trial evaluated 966 patients. All patients received Cosentyx 150 mg or 300 mg doses at weeks 0, 1, 2, 3, 4, 8 and 12 and then were randomised to receive either a maintenance regimen of the same dose every month starting at Week 12 or a "retreatment as needed" regimen of the same dose.

Results.

The 300 mg dose provided improved skin clearance across efficacy endpoints of PASI 75/90/100, and IGA mod 2011 'clear' or 'almost clear' responses across all studies with peak effects seen at week 16 (see Table 8 and Table 9). Therefore the 300 mg dose is recommended.
Cosentyx was efficacious in patients naive to biological medicines and in patients who had prior exposure to biological medicines, including anti-TNFs.
Cosentyx was associated with a fast onset of efficacy as shown in Figure 1 with a 50% reduction in mean PASI by week 3 for 300 mg.
An additional psoriasis study (CLEAR) evaluated 676 patients. Secukinumab 300 mg met the primary and secondary endpoints by showing superiority to ustekinumab based on PASI 90 response at Week 16 and speed of onset of PASI 75 response at Week 4, and long term PASI 90 response at Week 52. Greater efficacy of secukinumab compared to ustekinumab for the endpoints PASI 75/90/100 and IGA mod 2011 0 or 1 response ("clear" or "almost clear") was observed early and continued through to Week 52. In this study, each 300 mg dose was administered as two injections of 150 mg. See Table 10.
All plaque psoriasis phase III studies included approximately 15 to 25% of patients with concurrent psoriatic arthritis at baseline. Improvements in PASI 75 in this patient population were similar to those in the overall plaque psoriasis population.
In the subset of psoriatic arthritis patients in the ERASURE and FIXTURE studies, physical function was assessed using the HAQ Disability Index (HAQ-DI). In these studies, patients treated with 150 mg or 300 mg Cosentyx showed greater improvement from baseline in the HAQ-DI score (mean decreases of -27.5% and -50.2% at week 12) compared to placebo (-8.9%). This improvement was maintained up to week 52.
Patients in the SCULPTURE study that were randomised after week 12 to a "retreatment as needed" maintenance regimen did not achieve adequate maintenance of response to either dose used. After 52 weeks of treatment patients with 300 mg "retreatment as needed" regimen achieved a PASI 75 of 41.0% and a PASI 90 of 13.8%, whereas patients with a monthly maintenance regimen of 300 mg achieved a PASI 75 of 78.2% and a PASI 90 of 59.7%. Similarly, patients with 150 mg "retreatment as needed" regimen achieved a PASI 75 of 35.0% and a PASI 90 of 11.2%, whereas patients with a monthly maintenance regimen of 150 mg achieved a PASI 75 of 62.1% and a PASI 90 of 45.8% after 52 weeks of treatment. Therefore a fixed monthly maintenance regimen is recommended.

Specific locations/forms of plaque psoriasis.

In two additional placebo-controlled studies, improvement was seen in both nail psoriasis (TRANSFIGURE, 198 patients) and palmoplantar plaque psoriasis (GESTURE, 205 patients). In the TRANSFIGURE study, secukinumab was superior to placebo at Week 16 (46.1% for 300 mg, 38.4% for 150 mg and 11.7% for placebo) as assessed by significant improvement from baseline in the Nail Psoriasis Severity Index (NAPSI %) for patients with moderate to severe plaque psoriasis with nail involvement. In the GESTURE study, secukinumab was superior to placebo at Week 16 (33.3% for 300 mg, 22.1% for 150 mg, and 1.5% for placebo) as assessed by significant improvement of the Palmoplantar Investigator's Global Assessment (ppIGA) 0 or 1 response ("clear" or "almost clear") for patients with moderate to severe palmoplantar plaque psoriasis. In these studies, each 300 mg dose was given as two subcutaneous injections of 150 mg.
The placebo-controlled SCALP study evaluated 102 patients with moderate to severe scalp psoriasis, defined as having a Psoriasis Scalp Severity Index (PSSI) score of ≥ 12, an IGA mod 2011 scalp only score of 3 or greater and at least 30% of the scalp surface area affected. In this study, 62% of patients had at least 50% of the scalp surface area affected. Secukinumab 300 mg was superior to placebo at Week 12 as assessed by significant improvement from baseline in both the PSSI 90 response (52.9% vs. 2.0%) and IGA mod 2011 0 or 1 scalp only response (56.9% vs. 5.9%). Greater efficacy of secukinumab 300 mg over placebo for both endpoints was observed by Week 3. Improvement in both endpoints was sustained for secukinumab patients who continued treatment through to Week 24 (PSSI 90 response 58.8% and IGA mod 2011 0 or 1 scalp only response 62.7%). In these studies, each 300 mg dose was given as two subcutaneous injections of 150 mg.

Quality of life/patient reported outcomes.

Statistically significant improvements at week 12 (Studies 1-4) from baseline compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index), these improvements were maintained for 52 weeks (Studies 1 and 2).
Statistically significant improvements at week 12 from baseline compared to placebo (ERASURE and FIXTURE Studies) in patient reported signs and symptoms of itching, pain and scaling were demonstrated in the validated Psoriasis Symptom Diary.
Statistically significant improvements at Week 4 from baseline in patients treated with secukinumab compared to patients treated with ustekinumab (CLEAR) were demonstrated in the DLQI, and these improvements were maintained for up to 52 weeks. The Work Productivity and Activity Impairment Questionnaire-Psoriasis outcomes (WPAI-PSO) showed generally greater improvement in patients treated with secukinumab compared to patients treated with ustekinumab.
Statistically significant improvements in patient reported signs and symptoms of itching, pain and scaling at Week 16 and Week 52 (CLEAR) were demonstrated in the Psoriasis Symptom Diary in patients treated with secukinumab compared to patients treated with ustekinumab.
Statistically significant improvements at Week 12 from baseline compared to placebo (SCALP) were demonstrated in Health Related Quality of Life as measured by Scalpdex. These improvements were observed starting at Week 4 and were maintained through to Week 24.
Statistically significant improvements (decreases) at Week 12 from baseline (SCALP) were demonstrated in patient-reported signs and symptoms of scalp itching, pain, and scaling, compared to placebo.

Plaque psoriasis dose flexibility.

The efficacy, safety, and tolerability of Cosentyx 300 mg administered every 4 weeks vs. Cosentyx 300 mg administered every 2 weeks in adult patients weighing ≥ 90 kg with moderate to severe plaque psoriasis were assessed in a randomised, double-blind, multicentre study of 331 patients. Patients were randomised 1:1 as follows:
Secukinumab 300 mg at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 2 weeks up to Week 52 (n = 165).
Secukinumab 300 mg at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks up to Week 16 (n = 166).
Patients randomised to receive secukinumab 300 mg every 4 weeks who were PASI 90 responders at Week 16 continued to receive the same dosing regimen up to Week 52. Patients randomised to receive Cosentyx 300 mg every 4 weeks who were PASI 90 non-responders at Week 16 either continued on the same dosing regimen, or were reassigned to receive Cosentyx 300 mg every 2 weeks up to Week 52.
The primary and key secondary endpoints were the proportion of patients who achieved a PASI 90 response and IGA mod 2011 'clear' or 'almost clear' (0 or 1) response at Week 16. At Week 16, the proportion of patients who were PASI 90 responders was higher in the group treated with the every 2 week regimen vs. the every 4 week regimen (73.2% vs. 55.5%, respectively). The treatment difference was clinically relevant and statistically significant (one-sided p-value = 0.0003). The proportion of patients who achieved an IGA mod 2011 'clear' or 'almost clear' response was also higher but not statistically different from the group treated with the every 2 week regimen vs. the group treated with the every 4 week regimen (74.2% vs. 65.9%, respectively).
Patients on the every 2 week regimen vs. the every 4 week regimen (Figure 2) showed overall benefit, and benefit for some of the subgroups (weight, IGA, and time since diagnosis). The highest incremental benefit as shown by the calculated risk differences was for patients with severe disease (IGA 4).
The safety profiles of the two dosing regimens, Cosentyx 300 mg administered every 4 weeks and Cosentyx 300 mg administered every 2 weeks, in patients weighing ≥ 90 kg were comparable and consistent with the safety profile reported in psoriasis patients.
In the PASI 90 non-responders at week 16 who were up-titrated to secukinumab 300 mg Q2W, the PASI 90 response rates improved compared to those who remained on the secukinumab 300 mg Q4W dosing regimen, while the IGA mod 2011 0/1 response rates remained stable over time in both treatment groups.

300 mg/2 mL pre-filled syringe and 300 mg/2 mL pre-filled pen.

The results of the studies ALLURE and MATURE showed similar safety, efficacy, and overall patient experience in patients that received one injection of 300 mg and those that received 2 injections of 150 mg, with both the PFS and AI device.
Paediatric patients. The safety and efficacy of Cosentyx in paediatric plaque psoriasis patients aged 6 to less than 18 years were assessed in two phase III studies, A2310 (severe psoriasis) and A2311 (moderate to severe psoriasis). The age and weigh distribution is presented in Table 11.

Severe plaque psoriasis.

A 52-week, randomised, double-blind, placebo and etanercept-controlled phase III study enrolled 162 paediatric patients 6 to less than 18 years of age, with severe plaque psoriasis (as defined by a PASI score ≥ 20, an IGA mod 2011 score of 4, and involving ≥ 10% of the body surface area) who were candidates for systemic therapy. Approximately 43% had prior exposure to phototherapy, 53% to conventional systemic therapy, 3% to biological medicines, and 9% had concomitant psoriatic arthritis.
Patients were randomised to receive one of the following four treatments:
low dose secukinumab (75 mg for body weight < 50 kg or 150 mg for body weight ≥ 50 kg) at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks;
high dose secukinumab (75 mg for body weight < 25 kg, 150 mg for body weight ≥ 25 kg and < 50 kg, or 300 mg for body weight ≥ 50 kg) at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks;
placebo at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks;
etanercept (0.8 mg/kg) weekly (up to a maximum of 50 mg).
Patients randomised to receive placebo who were non-responders at Week 12 were switched to either the secukinumab low or high dose group (dose based on body weight group) and received study drug at Weeks 12, 13, 14, and 15, followed by the same dose every 4 weeks starting at Week 16.
The co-primary endpoints were the proportion of patients who achieved a reduction in PASI score of at least 75% (PASI 75) and IGA mod 2011 'clear' or 'almost clear' (0 or 1) with at least a 2 point improvement from baseline to Week 12. The key secondary endpoint was the proportion of patients who achieved a reduction in PASI score of at least 90% (PASI 90) from baseline to Week 12. Other secondary endpoints included PASI 50, 100 responder rates at Week 12, PASI 50, 75, 90, 100 and IGA 0/1 responder rates at Week 16 and over time up to and including Week 52, change in PASI score over time up to and including Week 52 and IGA score over time up to and including Week 52, the proportion of patients with a Children's Dermatology Life Quality Index (CDLQI) score of 0 or 1 at Week 12 and over time up to and including Week 52, and change from baseline in CDLQI compared to placebo at Week 12 and over time up to and including Week 52.
At Week 12 the efficacy of both the low and the high dose of secukinumab was comparable for the co-primary endpoints. The odds ratio estimates in favor of both secukinumab doses were clinically relevant and statistically significant for both the PASI 75 and IGA mod 2011 'clear' or 'almost clear' (0 or 1) responses.
All patients were followed for efficacy and safety during the 52 weeks following the first dose. The proportion of patients achieving PASI 75 and IGA mod 2011 'clear' or 'almost clear' (0 or 1) responses showed separation between secukinumab treatment groups and placebo at the first post-baseline visit at Week 4, the difference becoming more prominent at Week 12. The response was maintained throughout the 52 week time period. Improvement in PASI 50, 90, 100 responder rates and CDLQI 0 or 1 scores were also maintained throughout the 52 week time period.
Beyond Week 12, efficacy of both the low and the high dose of secukinumab was comparable although the efficacy of the high dose was higher for patients ≥ 50 kg. The safety profiles of the low dose and the high dose were comparable.
The efficacy results at Week 12 are presented in Table 12.
A higher proportion of paediatric patients treated with secukinumab reported improvement in health-related quality of life as measured by a CDLQI score of 0 or 1 compared to placebo at Week 12 (low dose 44.7%, high dose 50%, placebo 15%). This improvement was further maintained through Week 52.

Moderate to severe plaque psoriasis.

An open label, two-arm, parallel group, multicentre phase III study enrolled 84 paediatric patients 6 to less than 18 years of age with moderate to severe plaque psoriasis (as defined by a PASI score ≥ 12, an IGA mod 2011 score of ≥ 3, and involving ≥ 10% of the body surface area) who were candidates for systemic therapy.
Patients were randomised to receive secukinumab at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks as follows:
low dose secukinumab (75 mg for body weight < 50 kg or 150 mg for body weight ≥ 50 kg);
high dose secukinumab (75 mg for body weight < 25 kg, 150 mg for body weight between ≥ 25 kg and < 50 kg, or 300 mg for body weight ≥ 50 kg).
The co-primary endpoints were the proportion of patients who achieved a reduction in PASI score of at least 75% (PASI 75) and IGA mod 2011 'clear' or 'almost clear' (0 or 1) with at least a 2 point improvement from baseline to Week 12. Secondary endpoints included PASI 90 response at Week 12.
The efficacy of both the low and the high dose of secukinumab was comparable and showed statistically and clinically meaningful improvement compared to historical placebo for the co-primary endpoints. The odds ratio estimates in favor of both secukinumab doses were clinically relevant and statistically significant for both the PASI 75 and IGA mod 2011 0 or 1 responses versus historical placebo. The estimated posterior probability of a positive treatment effect was 100%.
The efficacy results at Week 12 are presented in Table 13.
Psoriatic arthritis. The safety and efficacy of Cosentyx were assessed in 1,999 patients in three randomised, double-blind, placebo-controlled phase III studies in patients with active psoriatic arthritis (≥ 3 swollen and ≥ 3 tender joints) despite non-steroidal anti-inflammatory drug (NSAID), corticosteroids or disease-modifying anti-rheumatic drug (DMARD) therapy. Patients with each subtype of PsA were enrolled in these studies, including polyarticular arthritis with no evidence of rheumatoid nodules, spondylitis with peripheral arthritis, asymmetric peripheral arthritis, distal interphalangeal involvement and arthritis mutilans. Patients in these studies had a diagnosis of PsA for a median of 3.9 to 5.3 years. Approximately half of all enrolled patients had at least 3% BSA involvement with skin psoriasis at baseline. Over 61% and 42% of the PsA patients had enthesitis and dactylitis at baseline, respectively.
In FUTURE 1 study (PsA1 study), FUTURE 2 study (PsA2 study), and FUTURE 5 study (PsA3 study), 29%, 35%, and 30% of patients, respectively, were previously treated with an anti-TNF-alpha agent and discontinued the anti-TNF-alpha agent for either lack of efficacy or intolerance (anti-TNF-alpha-IR patients). For FUTURE 1 and FUTURE 2, the primary endpoint was American College of Rheumatology (ACR) 20 response at Week 24. The primary endpoint for FUTURE 5 was ACR 20 response at Week 16, and the key secondary endpoint was the change from baseline in modified Total Sharp Score (mTSS) at Week 24.
Key exclusion criteria across pivotal trials were: use of high potency opioid analgesics; ongoing use of certain psoriasis treatments, e.g. topical or systemic corticosteroids or UV therapy; previous exposure to secukinumab or any other biological medicines for psoriasis and PsA except for those targeting TNF-α, patients with active, ongoing inflammatory disease other than PsA; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA Class III and IV); patients with serum creatinine > 132.6 micromol/L or with white blood cell count < 3,000/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of child-bearing potential not using effective contraception during the study.

FUTURE 1 study (F2306).

PsA1 study evaluated 606 patients, of whom 60.7% had concomitant MTX. Patients randomised to Cosentyx received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every month starting at Week 8. Patients randomised to receive placebo who were non-responders at Week 16 (early rescue) and other placebo patients at Week 24 were crossed over to receive Cosentyx (either 75 mg or 150 mg) at Week 16 followed by the same dose every month.

FUTURE 2 study (F2312).

PsA2 study evaluated 397 patients, of whom 46.6% had concomitant MTX. Patients randomised to Cosentyx received 75 mg, 150 mg or 300 mg s.c. at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients randomised to receive placebo who were non-responders at Week 16 (early rescue) were then crossed over to receive Cosentyx (either 150 mg or 300 mg, s.c.) at Week 16 followed by the same dose every month. Patients randomised to receive placebo who were responders at Week 16 were crossed over to receive Cosentyx (either 150 mg or 300 mg) at Week 24 followed by the same dose every month.

FUTURE 5 study (F2342).

PsA3 study evaluated 996 patients, of whom 50.1% had concomitant MTX treatment. Patients were randomised to receive Cosentyx 150 mg, 300 mg, or placebo s.c. at Weeks 0, 1, 2, 3 and 4 followed by the same dose every month, or a once monthly injection of Cosentyx 150 mg (without loading). Patients randomised to receive placebo who were non-responders at Week 16 were then crossed over to receive Cosentyx (either 150 mg or 300 mg, s.c.) at Week 16 followed by the same dose every month. Patients randomised to receive placebo who were responders at Week 16 were crossed over to receive Cosentyx (either 150 mg or 300 mg) at Week 24 followed by the same dose every month. The total combined duration of treatment for PsA3 study is 2 years.

Signs and symptoms.

Treatment with Cosentyx resulted in significant improvement in the measure of disease activity compared to placebo at Weeks 16 and 24. (See Table 14.)
The onset of action of Cosentyx occurred as early as Week 2. Statistically significant difference in ACR 20 vs placebo was reached at Week 3. In PsA2 efficacy responses were maintained up to Week 104. At Week 16, Cosentyx treated patients demonstrated significant improvements in signs and symptoms among which significantly higher responses in ACR 20 (60.0% and 57.0% for 150 mg and 300 mg, respectively) compared to placebo (18.4%).
The percentage of patients achieving ACR 20 response by visit is shown in Figure 3.
Similar responses for primary and key secondary endpoints were seen in PsA patients regardless of whether they were on concomitant MTX treatment or not.
Both, anti-TNF-alpha-naïve and anti-TNF-alpha-IR Cosentyx treated patients, had a significantly higher ACR 20 response compared to placebo at Week 24, with a slightly higher response in the anti-TNF-alpha-naïve group in the PsA2 study (anti-TNF-alpha-naïve: 64% and 58% for 150 mg and 300 mg, respectively, compared to placebo 15.9%; anti-TNF-alpha-IR: 30% and 46% for 150 mg and 300 mg, respectively, compared to placebo 14.3%). Anti-TNF-alpha-IR patients on 300 mg showed higher response rates on ACR 20 compared to placebo patients (p < 0.05) and demonstrated clinical meaningful benefit over 150 mg on multiple secondary endpoints. Improvements in the PASI 75 response were seen in both subgroups and the 300 mg dose showed statistically significant benefit in the anti-TNF-alpha-IR patients.
Improvements were shown in all components of the ACR scores, including patient assessment of pain. The proportion of patients achieving a modified PsA Response Criteria (PsARC) response was greater in the Cosentyx treated patients (59.0% and 61.0% for 150 mg and 300 mg, respectively) compared to placebo (26.5%) at Week 24.
In PsA1 study and PsA2 study, efficacy was maintained up to Week 52. In PsA2 study, among 200 patients initially randomised to Cosentyx 150 mg and 300 mg, 178 (89%) patients were still on treatment at Week 52. Of the 100 patients randomised to Cosentyx 150 mg, 64, 39 and 20 had an ACR 20/50/70 response, respectively. Of the 100 patients randomised to Cosentyx 300 mg, 64, 44 and 24 had an ACR 20/50/70 response, respectively.

Radiographic response.

In PsA3 study, inhibition of progression of structural damage was assessed radiographically and expressed by the modified Total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing Score (JSN). Radiographs of hands, wrists, and feet were obtained at baseline Week 16 and/or Week 24 and scored independently by at least two readers who were blinded to treatment group and visit number.
Cosentyx 150 mg and 300 mg treatment significantly inhibited the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS at Week 24 (see Table 15).
The percentage of patients with no disease progression (defined as a change from baseline in mTSS of ≤ 0.5) from randomisation to Week 24 was 80.3%, 88.5% and 73.6% for Cosentyx 150 mg, 300 mg and placebo, respectively. An effect of inhibition of structural damage was observed irrespective of concomitant MTX use or TNF status.
Structural damage was also assessed in the PsA1 study. Radiographs of hands, wrists, and feet were obtained at baseline and Week 24 during the double-blind period when patients were on Cosentyx or placebo and at Week 52 when all patients were on open-label Cosentyx.
By Week 24, Cosentyx 150 mg treatment significantly inhibited the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS (see Table 15). Inhibition of structural damage was maintained with Cosentyx treatment up to Week 52.
In PsA1 study, the inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified Total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at Weeks 24 and 52, compared to baseline Week 24 data presented in Table 15.
Inhibition of structural damage was maintained with Cosentyx 150 mg treatment up to Week 104 in PsA2 study and with Cosentyx 300 mg treatment up to week 52 in PsA3 study.
The percentage of patients with no-disease progression (defined as a change from baseline in mTSS of ≤ 0.5) from randomisation to Week 24 was, 82.3% in secukinumab 10 mg/kg i.v. load - 150 mg s.c. maintenance and 75.7% in placebo. The percentage of patients with no-disease progression, from Week 24 to Week 52, for the same above described regimen, was 85.7% and 86.8%, respectively.

Axial manifestations in PsA.

A randomised, double-blind, placebo-controlled study (MAXIMISE) assessed the efficacy of secukinumab in 485 PsA patients with axial manifestations who were naive to biological medicine treatment and responded inadequately to NSAIDs. The primary variable of at least a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) criteria at Week 12 was met (see Table 16).
Improvement in ASAS 20 for both secukinumab doses were observed by Week 4 and were maintained up to 52 weeks.
In addition, treatment with secukinumab 300 mg and 150 mg compared to placebo also resulted in greater improvement in signs and symptoms (including decreases from baseline in spinal pain and improvement in physical function) as seen in Table 17.

Physical function and health related quality of life.

In PsA2 and PsA3 Studies, patients treated with Cosentyx 150 mg and 300 mg showed improvement in physical function compared to patients treated with placebo as assessed by change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 and Week 16, respectively. In PsA3 study, the change from baseline in HAQ-DI was -0.44 and -0.55 for Cosentyx 150 mg and 300 mg, respectively, versus -0.21 for placebo (< 0.0001). Improvements in HAQ-DI scores were seen regardless of previous anti-TNF-alpha exposure.
Cosentyx-treated patients reported significant improvements in health-related quality of life as measured by the Short Form (36) Health Survey Physical Component Summary (SF 36 PCS) score (p < 0.001) and these improvements were maintained up to Week 104 in PsA2.
Axial spondyloarthritis (axSpA) with or without radiographic damage. Ankylosing spondylitis (axSpA with radiographic damage). The safety and efficacy of Cosentyx were assessed in 816 patients in three randomised, double-blind, placebo-controlled phase III studies in patients with active ankylosing spondylitis (AS) with a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. Patients in the AS1 study and AS2 study had a diagnosis of AS for a median of 2.7 to 5.8 years.
In MEASURE 1 study (AS1 study), MEASURE 2 study (AS2 study), and MEASURE 3 study (AS3 study), 27.0%, 38.8%, and 23.5% of patients, respectively, were previously treated with an anti-TNF-alpha agent and discontinued the anti-TNF-α agent for either lack of efficacy or intolerance (anti-TNF-alpha-IR patients).
Key exclusion criteria across pivotal trials were: patients with total ankylosis of the spine; use of high potency opioid analgesics; previous exposure to secukinumab or any other biological medicines except for those targeting TNF-alpha, patients with active, ongoing inflammatory disease, other than AS; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA Class III and IV); patients with serum creatinine > 132.6 micromol/L or with white blood cell count < 3,000/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of child-bearing potential not using effective contraception during the study.
AS1 study evaluated 371 patients, of whom 14.8% and 33.4% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every month starting at week 8. Patients randomised to placebo who were non-responders at Week 16 (early rescue) and all other placebo patients at Week 24 were crossed over to receive Cosentyx (either 75 mg or 150 mg s.c.), followed by the same dose every month. The primary endpoint was at least a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) criteria at Week 16.
AS2 study evaluated 219 patients, of whom 11.9% and 14.2% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 75 mg or 150 mg s.c. at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. At Week 16, patients who were randomised to placebo at baseline were re-randomised to receive Cosentyx (either 75 mg or 150 mg) s.c. every month. The primary endpoint was ASAS 20 at Week 16.
AS3 study evaluated 226 patients, of whom 13.3% and 23.5% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed by either 150 mg or 300 mg s.c. every month. At Week 16, patients who were randomised to placebo at baseline were re-randomised to receive Cosentyx (either 150 mg or 300 mg) s.c. every month. The primary end point was ASAS 20 at Week 16. Patients were blinded to the treatment regimen up to Week 52, and the study continued to Week 156.

Signs and symptoms.

In AS2 study, treatment with Cosentyx 150 mg resulted in greater improvement in measures of disease activity compared with placebo at Week 16 (see Table 18).
The onset of action of Cosentyx 150 mg occurred as early as Week 1 for ASAS 20 and Week 2 for ASAS 40 (superior to placebo) in AS2 study. (See Figures 4 and 5).
ASAS 20 responses were improved at Week 16 in both anti-TNF-α naïve patients (68.2% vs. 31.1%; p < 0.05) and anti-TNF-α-IR patients (50.0% vs. 24.1%; p < 0.05) for Cosentyx 150 mg compared with placebo, respectively.
In AS1 study and AS2 study, Cosentyx treated patients (150 mg in AS2 study and both regimens in AS1 study) demonstrated significantly improved signs and symptoms at Week 16, with comparable magnitude of response and efficacy was maintained up to Week 52 in both anti-TNF-alpha-naïve and anti-TNF-alpha-IR patients. In AS study 2, among 72 patients initially randomised to Cosentyx 150 mg, 61 (84.7%) patients were still on treatment at Week 52. Of the 72 patients randomised to Cosentyx 150 mg, 45 and 35 had ASAS 20/40 response, respectively.
In AS3 study, Cosentyx treated patients (150 mg and 300 mg) demonstrated improved signs and symptoms, and had comparable efficacy responses regardless of dose that were superior to placebo at Week 16 for the primary endpoint (ASAS 20). Greater response rates favouring 300 mg were also observed for ASAS partial remission (ASAS PR) response at week 16. During the blinded period, the ASAS 20 and ASAS 40 responses were 69.7% and 47.6% for 150 mg and 74.3% and 57.4% for 300 mg at week 52, respectively. The ASAS 20 and ASAS 40 responses were maintained through Week 156 (69.5% and 47.6% for 150 mg vs. 74.8% and 55.6% for 300 mg). The ASAS partial remission (ASAS PR) responses were 9.5% and 21.1% for 150 mg and 300 mg respectively, compared to 1.3% for placebo at Week 16. The ASAS PR responses were 18.1% and 24.3% for 150 mg and 300 mg at Week 52, respectively. These responses were maintained through Week 156 (15.1% for 150 mg and 27.2% for 300 mg).

Spinal mobility.

Patients treated with Cosentyx 150 mg showed improvements in spinal mobility as measured by change from baseline in BASMI at Week 16 for both AS study 1 (0.40 versus 0.12 for placebo; p = 0.0114) and AS study 2 (0.51 versus 0.22 for placebo; p = 0.0533). These improvements were sustained up to Week 52.

Physical function and health related quality of life.

In AS study 1 and 2, patients treated with Cosentyx 150 mg showed improvements in health related quality of life as measured by ASQoL (p = 0.001) and SF-36 PCS (p < 0.001). These improvements were sustained up to Week 52.
Patients treated with Cosentyx 150 mg also showed improvements on exploratory endpoints in physical function as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) compared to placebo (-2.15 versus -0.68).
Non-radiographic axial spondyloarthritis (axSpA without radiographic damage). The safety and efficacy of Cosentyx were assessed in 555 patients in one randomised, double-blind, placebo-controlled phase III study in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) fulfilling the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) with no radiographic evidence of changes in the sacroiliac joints that would meet the modified New York criteria for ankylosing spondylitis (AS). Patients enrolled had active disease, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, a Visual Analogue Scale (VAS) for total back pain of ≥ 40 (on a scale of 0-100 mm), despite current or previous non-steroidal anti-inflammatory drug (NSAID) therapy and increased C-reactive protein (CRP) and/or evidence of sacroiliitis on Magnetic Resonance Imaging (MRI). Patients in this study had a diagnosis of axSpA for a mean of 2.1 to 3.0 years and 54% of the study participants were female.
In nr-axSpA 1 study, 57.6% of patients had increased CRP, 72.2% had evidence of sacroiliitis on MRI and 29.9% had both increased CRP and evidence of sacroiliitis on MRI. In addition, 9.7% of patients were previously treated with an anti-TNF-alpha agent and discontinued the anti-TNF-alpha agent for either lack of efficacy or intolerance (anti-TNF-alpha-IR patients).
Nr-axSpA 1 Study (PREVENT) evaluated 555 patients, of whom 9.9% and 14.8% used concomitant MTX or sulfasalazine, respectively. In the double-blind period, patients received either placebo or Cosentyx for 52 weeks. Patients randomised to Cosentyx received 150 mg s.c. at Weeks 0, 1, 2, 3 and 4 followed by the same dose every four weeks, or Cosentyx 150 mg s.c. every four weeks without a loading dose. The primary endpoint was at least 40% improvement in ASAS 40 at Week 16 in TNF-naive patients.

Clinical response. Signs and symptoms.

In nr-axSpA1 study, treatment with Cosentyx 150 mg resulted in significant improvements in the measures of disease activity compared to placebo at Week 16. These measures include ASAS 40, ASAS 5/6, BASDAI score, BASDAI 50, high-sensitivity CRP (hsCRP), ASAS 20 and ASAS partial remission response compared to placebo at Week 16 (see Table 19).
The onset of action of Cosentyx 150 mg occurred as early as Week 3 for ASAS 40 in anti-TNF-alpha naive patients (superior to placebo) in nr-axSpA1 study. The percentage of patients achieving an ASAS 40 response in anti-TNF-alpha naive patients by visit is shown in Figure 6. Patients treated with Cosentyx maintained their response compared to placebo up to Week 52.
ASAS 40 responses were also improved at Week 16 in anti-TNF-alpha-IR patients (28.6% vs. 13.3%) for Cosentyx 150 mg compared with placebo. The magnitude of response (treatment difference versus placebo) with respect to signs and symptoms at Week 16 was similar in anti-TNF-alpha-naïve and anti-TNF-alpha-IR patients, with higher absolute response rates in anti-TNF-alpha-naïve patients. Efficacy versus placebo was maintained in anti-TNF-alpha-naïve and anti-TNF-alpha-IR patients up to Week 52.

Physical function and health-related quality of life.

Patients treated with Cosentyx 150 mg showed statistically significant improvements by Week 16 compared to placebo-treated patients in physical function as assessed by the BASFI (Week 16: -1.75 vs -1.01, p < 0.05). Patients treated with Cosentyx reported significant improvements compared to placebo-treated patients by Week 16 in health-related quality of life as measured by ASQoL (LS mean change: Week 16: -3.45 vs -1.84, p < 0.05) and SF-36 Physical Component Summary (SF-36 PCS) (LS mean change: Week 16: 5.71 vs 2.93, p < 0.05). These improvements were sustained up to Week 52.

Spinal mobility.

Spinal mobility was assessed by BASMI up to Week 16. Numerically greater improvements were demonstrated in patients treated with Cosentyx compared with placebo-treated patients at Weeks 4, 8, 12 and 16.

Inhibition of inflammation in magnetic resonance imaging (MRI).

Signs of inflammation were assessed by MRI at baseline and Week 16 and expressed as change from baseline in Berlin SI-joint oedema score for sacroiliac joints and ASspiMRI-a score and Berlin spine score for the spine. Inhibition of inflammatory signs in both sacroiliac joints and the spine was observed in patients treated with secukinumab. Mean change from baseline in Berlin SI-joint oedema score was -1.68 for patients treated with Cosentyx 150 mg (n = 180) versus -0.39 for the placebo-treated patients (n = 174) (p < 0.05).
Juvenile idiopathic arthritis (JIA).

Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA).

The efficacy and safety of secukinumab were assessed in 86 patients in a 3-part, double-blind, placebo-controlled, event-driven, randomized, Phase III study in patients 2 to < 18 years of age with active ERA or JPsA as diagnosed based on a modified International League of Associations for Rheumatology (ILAR) JIA classification criteria. The study consisted of an open-label portion (Part 1), followed by randomised withdrawal (Part 2), followed by open-label treatment (Part 3). The JIA patient subtypes at study entry were: 60.5% ERA and 39.5% JPsA. In the study 67.6% of patients with JPsA, and 63.5% of patients with ERA, were treated concomitantly with MTX. Patients were given a dose of 75 mg if weighing < 50 kg, or 150 mg if weighing ≥ 50 kg.
The primary endpoint was time to flare in Part 2. Disease flare was defined as a ≥ 30% worsening in at least three of the six JIA ACR response criteria and ≥ 30% improvement in not more than one of the six JIA ACR response criteria and a worsening of a minimum of two active joints (if the number of joints is one of the variables used to define flare).
In open-label Part 1, all patients received secukinumab until Week 12. Patients classified as responders at Week 12 entered into the Part 2 double-blind phase and were randomized 1:1 to continue treatment with secukinumab or begin treatment with placebo.
The study met its primary endpoint by demonstrating a statistically significant prolongation in the time to disease flare in patients treated with secukinumab compared to placebo. The risk of flare was reduced by 72% for patients on secukinumab compared with patients on placebo (Hazard Ratio of flare events = 0.28, 95% CI: 0.13 to 0.63, p < 0.001) (Figure 7). During Part 2, a total of 21 patients in the placebo group experienced a flare event (11 JPsA and 10 ERA) compared with 10 patients in the secukinumab group (4 JPsA and 6 ERA).
Hidradenitis suppurativa. The safety and efficacy of secukinumab were assessed in 1,084 patients in two similar randomised, double-blind, placebo-controlled phase III studies in adult patients with moderate to severe hidradenitis suppurativa (HS) who were candidates for systemic therapy with biological medicines. Patients enrolled in HS study 1 (SUNSHINE) and HS study 2 (SUNRISE) had Hurley stage I (4.6% and 2.8%, respectively), II (61.4% and 56.7%, respectively) or III (34.0% and 40.5%, respectively) disease at baseline with at least five inflammatory lesions affecting two anatomical areas. The proportion of patients weighing ≥ 90 kg was 54.7% in HS study 1 and 50.8% in HS study 2. Patients in these studies had a diagnosis of moderate to severe HS for a mean of 7.3 years and 56.3% of the study participants were female. In HS study 1 and HS study 2, 23.8% and 23.2% of patients, respectively, were previously treated with a biological medicine and discontinued the biological agent for either lack of efficacy or intolerance (bio-exposed patients).
HS study 1 (SUNSHINE) evaluated 541 patients and HS study 2 (SUNRISE) evaluated 543 patients, of whom 12.8% and 10.7%, respectively, received concomitant stable dose of antibiotics. In both studies, patients randomised to secukinumab received 300 mg subcutaneously at Weeks 0, 1, 2, 3 and 4, followed by 300 mg every 2 weeks (Q2W) or every 4 weeks (Q4W). At Week 16, patients who were randomised to placebo were reassigned to receive secukinumab 300 mg at Weeks 16, 17, 18, 19 and 20 followed by either secukinumab 300 mg every 2 weeks (Q2W) or secukinumab 300 mg every 4 weeks (Q4W).
The primary endpoint in both studies (HS study 1 and HS study 2) was the proportion of patients achieving a hidradenitis suppurativa clinical response defined as at least a 50% decrease in abscesses and inflammatory nodules count with no increase in the number of abscesses and/or in the number of draining fistulae relative to baseline (HiSCR50) at Week 16. Reduction in HS-related skin pain was assessed as a secondary endpoint on the pooled data of HS study 1 and HS study 2 using a numerical rating scale (NRS) in patients who entered the studies with an initial baseline score of 3 or greater.
In HS study 1 and HS study 2, a higher proportion of patients treated with secukinumab 300 mg Q2W or 300 mg Q4W achieved a HiSCR50 response and a decrease in abscesses and inflammatory nodules (AN) count compared to placebo at Week 16. In both studies, a lower proportion of patients experienced flares up to Week 16 with secukinumab 300 mg Q2W or 300 mg Q4W. A higher proportion of patients treated with secukinumab at either dose (pooled data) experienced a clinically relevant decrease in HS-related skin pain compared to placebo at Week 16 (Table 20).
In both studies, the onset of action of secukinumab occurred as early as Week 2, the efficacy progressively increased to Week 16 and was maintained up to Week 52.
Improvements were seen for the primary and key secondary endpoints in HS patients regardless of previous or concomitant antibiotic treatment.
HiSCR50 responses were numerically similar at Week 16 in trial participants who had previous exposure to biological medicines and those who were naive to biological medicines.
Greater improvements at Week 16 from baseline compared to placebo were demonstrated in health-related quality of life as measured by the Dermatology Life Quality Index.

5.2 Pharmacokinetic Properties

The mean pharmacokinetic parameters of secukinumab following single and multiple subcutaneous administration in adult patients with psoriasis, resulting from population pharmacokinetic analysis, are shown in Table 22. Cmax and AUC were dose proportional at 150 mg and 300 mg subcutaneous doses.

Pharmacokinetics in special patient groups.

Paediatrics.

Plaque psoriasis.

In a pool of the two paediatric studies, patients with severe or moderate to severe plaque psoriasis (6 to less than 18 years of age) were administered secukinumab at the recommended paediatric dosing regimen using the PFS device. At Week 24, patients weighing ≥ 25 and < 50 kg had a mean ± SD steady-state trough concentration of 19.8 ± 6.96 microgram/mL (n = 24) after 75 mg of secukinumab, and patients weighing ≥ 50 kg had a mean ± SD steady-state trough concentration of 27.3 ± 10.1 microgram/mL (n = 36) after 150 mg of secukinumab. The mean ± SD steady-state trough concentration in patients weighing < 25 kg (n = 8) was 32.6 ± 10.8 microgram/mL at Week 24 after 75 mg dose.

Juvenile idiopathic arthritis (JIA): enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA).

In a paediatric study, ERA and JPsA patients (2 to less than 18 years of age) were administered secukinumab at the recommended paediatric dosing regimen. At Week 24, patients weighing < 50 kg, and patients weighing ≥ 50 kg had a mean ± SD steady-state trough concentration of 25.2 ± 5.45 microgram/mL (n = 10) and 27.9 ± 9.57 microgram/mL (n = 19), respectively.
Elderly patients. Of the 3,430 plaque psoriasis patients exposed to Cosentyx in clinical studies, a total of 230 were 65 years of age or older and 32 patients were 75 years of age or older.
Of the 2,536 psoriatic arthritis patients exposed to Cosentyx in clinical studies, a total of 236 patients were 65 years of age or older and 25 patients were 75 years of age or older.
Of the 794 ankylosing spondylitis patients exposed to Cosentyx in clinical studies, a total of 29 patients were 65 years of age or older and 3 patients were 75 years of age or older.
Of the 524 non-radiographic axial spondyloarthritis patients exposed to Cosentyx in clinical studies, a total of 9 patients were 65 years of age or older and 2 patients were 75 years of age of older.
Of the 721 hidradenitis suppurativa patients exposed to Cosentyx in clinical studies, a total of 11 patients were 65 years of age or older and no patient was 75 years of age or older.
Based on population PK analysis, clearance in elderly patients and patients less than 65 years of age was similar.
Patients with renal and hepatic impairment. No pharmacokinetic data are available in patients with hepatic or renal impairment.
Effect of weight on pharmacokinetics. Secukinumab clearance and volume of distribution increase as bodyweight increases.

Absorption.

Following a single subcutaneous dose of either 150 mg or 300 mg administered as two injections of 150 mg in plaque psoriasis patients, secukinumab reached peak serum concentrations of 13.7 ± 4.8 microgram/mL or 27.3 ± 9.5 microgram/mL, respectively, between 5 to 6 days post dose.
After the initial weekly dosing during the first month, the time to reach the maximum concentration was between 31 and 34 days.
Peak concentrations at steady state (Cmax,ss) following subcutaneous administration of 150 mg or 300 mg were 27.6 microgram/mL and 55.2 microgram/mL, respectively. Steady state is reached after 20 weeks with monthly dosing regimens.
Compared with exposure after a single dose, patients exhibited a 2-fold increase in peak serum concentrations and AUC following repeated monthly dosing during maintenance.
Secukinumab is absorbed with an average absolute bioavailability of 73%.
Following multiple subcutaneous doses of 300 mg administered via the 300 mg/2 mL pen and/or pre-filled syringe in plaque psoriasis patients, the mean serum trough concentrations of secukinumab were consistent with those observed in the previous 150 mg/1 mL studies used to deliver 300 mg.
Following subcutaneous administrations of 300 mg at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 2 weeks, the mean ± SD steady-state secukinumab trough concentration at Week 16 was approximately 55.1 ± 26.7 microgram/mL and 58.1 ± 30.1 microgram/mL in HS study 1 and HS study 2, respectively.

Distribution.

The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in plaque psoriasis patients suggesting that secukinumab undergoes limited distribution to peripheral compartments.
Secukinumab concentrations in interstitial fluid in the skin of plaque psoriasis patients ranged from 28% to 39% of those in serum at 1 and 2 weeks after a single subcutaneous dose of 300 mg secukinumab (administered as two injections of 150 mg).

Metabolism.

The metabolic pathway of secukinumab has not been characterised. As a human IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Excretion.

Mean systemic clearance (CL) was 0.19 L/d in plaque psoriasis patients. Clearance was dose and time independent, as expected for a therapeutic IgG1 monoclonal antibody interacting with a soluble cytokine target, such as IL-17A.
The mean elimination half-life was estimated to be 27 days in plaque psoriasis patients. Estimated half-lives in individual plaque psoriasis patients range from 17 to 41 days.
In a population pharmacokinetic analysis, the mean systemic CL following subcutaneous administrations of 300 mg at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 2 weeks to patients with hidradenitis suppurativa was 0.26 L/day.
The mean elimination half-life, as estimated from population pharmacokinetic analysis, was 23 days in hidradenitis suppurativa patients.

Dose linearity.

The single and multiple dose pharmacokinetics of secukinumab in plaque psoriasis patients were determined in several studies with intravenous doses ranging from 1 x 0.3 mg/kg to 3 x 10 mg/kg and with subcutaneous doses ranging from 1 x 25 mg to multiple doses of 300 mg. Exposure was dose proportional across all dosing regimens.
The pharmacokinetics properties of secukinumab observed in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) patients were similar to those displayed in plaque psoriasis patients. The bioavailability of secukinumab in PsA patients was 85% on the basis of the population pharmacokinetic model.

5.3 Preclinical Safety Data

Genotoxicity.

Cosentyx has not been evaluated for genotoxic potential.

Carcinogenicity.

Secukinumab has not been evaluated for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Powder for injection.

Water for injections, sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 80.

Solution for injection.

Trehalose dihydrate, histidine, histidine hydrochloride monohydrate, polysorbate 80, methionine, water for injections.

6.2 Incompatibilities

Powder for solution.

Cosentyx should not be mixed with any medication or diluents other than sterile water for injection.

Solution for injection.

Cosentyx must not be mixed with other medicinal products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Powder for solution.

Store at 2-8°C. Store in the original package.

Pre-filled syringe.

Store at 2-8°C. Do not freeze. Protect from light.
Store in the original package.
May be stored unrefrigerated (out of fridge) for a single period up to a maximum of 4 days at room temperature below 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

Pre-filled pen.

Store at 2-8°C. Do not freeze. Protect from light.
Store in the original package.
May be stored unrefrigerated (out of fridge) for a single period up to a maximum of 4 days at room temperature below 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

6.5 Nature and Contents of Container

Cosentyx 150 mg powder for solution.

Secukinumab 150 mg as a sterile white solid lyophilisate for subcutaneous injection. Packs containing 1* or 2* single-use vials.

Cosentyx 75 mg/0.5 mL solution for injection in prefilled syringe.

Secukinumab 75 mg/0.5 mL solution for subcutaneous injection in a single use pre-filled syringe (PFS). The sterile solution is colourless to slightly yellow. Pack containing 1* pre-filled syringe.

Cosentyx 150 mg/1 mL solution for injection in prefilled syringe.

Secukinumab 150 mg/1 mL solution for subcutaneous injection in a single use pre-filled syringe (PFS). The sterile solution is colourless to slightly yellow. Packs containing 1* or 2* pre-filled syringes.

Cosentyx 300 mg/2 mL solution for injection in prefilled syringe.

Secukinumab 300 mg/2 mL solution for subcutaneous injection in a single use pre-filled syringe (PFS). The sterile solution is colourless to slightly yellow. Packs containing 1* pre-filled syringe.

Cosentyx 150 mg/1 mL solution for injection in prefilled pen.

Secukinumab 150 mg/1 mL solution for subcutaneous injection in a single use pre-filled pen. The sterile solution is colourless to slightly yellow. The pen consists of a PFS assembled into a pen with a removable rubber cap. Packs containing 1* or 2* pre-filled pens.

Cosentyx 300 mg/2 mL solution for injection in prefilled pen.

Secukinumab 300 mg/2 mL solution for subcutaneous injection in a single use pre-filled pen. The sterile solution is colourless to slightly yellow. The pen consists of a PFS assembled into a squared-shaped pen with transparent window and label. Pack containing 1 pre-filled pen.
* Not all pack sizes or presentations may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

The amino acid sequences of the light chain (215 amino acids) and the heavy chain (457 amino acids) respectively.
Molecular formula: C6584H10134N1754O2042S44.
Molecular weight: Approximately 148 kDa.

CAS number.

875356-43-7 (heavy chain), 875356-44-8 (light chain).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription medicine.

Summary Table of Changes