Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Kineret (Amgen)

100 mg/0.67 mL in pre-filled syringes

Approved indication: rheumatoid arthritis

Australian Medicines Handbook section 15.2.2

The current treatment of rheumatoid arthritis involves the early use of disease-modifying antirheumatic drugs (DMARDs).1 If these drugs are not effective a biological agent may be considered. These agents are aimed at the pro-inflammatory cytokines which are involved in the pathogenesis of rheumatoid arthritis.

The structure of anakinra differs by only one amino acid from the structure of the naturally occurring human interleukin-1 receptor antagonist. This difference is to enable genetically engineered Escherichia coli to produce anakinra.

Anakinra antagonises interleukin 1α and 1β at the interleukin-1 type 1 receptor. As these interleukins are inflammatory mediators, competition for their receptor may prevent joint damage.

Patients have to subcutaneously inject anakinra every day. The maximum plasma concentration is reached in 3-7 hours. Anakinra is probably cleared by the kidneys and has a half-life of 4-6 hours.

In a clinical trial involving 472 patients, anakinra was compared to injections of a placebo. After 24 weeks the rheumatoid arthritis was less active in patients randomised to receive anakinra. They had fewer swollen joints, less pain and a shorter duration of morning stiffness.2 This trial was extended for a year with patients from the placebo group being switched to treatment with anakinra. A total of 218 patients completed the extension. Efficacy was maintained in 46% of the patients who continued treatment with anakinra and 40% of the patients who had switched from placebo.3

During the extension phase 29% of the patients discontinued treatment. Half of these withdrawals were caused by adverse events such as a flare-up of the arthritis or abnormal blood counts.3

Adverse effects also accounted for most of the withdrawals from a safety study of anakinra. This study randomised 1414 patients to take anakinra or placebo in addition to their other treatments. Approximately 78% of the patients completed six months of treatment. The most common adverse effect of anakinra was injection site reactions. Patients should vary the site of injection to try and reduce such reactions. Serious infections such as pneumonia occurred more frequently than with placebo.4 Patients should have their white blood cell count checked before and during treatment.

Although the safety study4 included patients taking other DMARDs, anakinra is only approved in Australia for prescription with methotrexate. This combination was compared with methotrexate in a six-month study involving 419 patients. Adding anakinra produced a response in 38-46% which was significantly greater than the 19% of patients who responded to methotrexate alone.5

While the trials show that anakinra has greater efficacy than placebo its benefits depend on how efficacy is measured. Several trials used the American College of Rheumatology criteria for a 20% improvement (ACR20).6 However, if the criteria for success is set higher the results are less impressive. For example, if the goal is a 50% improvement in the patient's symptoms, only 18% of patients will achieve it. If the goal is a 70% improvement, only 3% will achieve it after 48 weeks of therapy.3

As the response may be related to the dose of anakinra5, it is important to know that some patients in the trials took more than the recommended daily dose of 100 mg. This dose was not specifically tested in some of the published trials.2,3,5

While the biological agents will benefit some of the patients who have not responded to DMARDs, the variations in study design mean the best option is not clear. Anakinra does not appear to be more effective than etanercept or infliximab, but comparative studies are needed. [cited 2004 Nov 8]