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.
Orencia (Bristol-Myers Squibb)
vials containing 250 mg lyophilised powder
Approved indication: rheumatoid arthritis
Australian Medicines Handbook section 15.2
The primary goal of treatment for rheumatoid arthritis is to preserve and restore physical function as well as modify the disease process and slow down the development of joint damage. In Australia, methotrexate is initially used to manage the disease. It is often given with other disease-modifying antirheumatic drugs (DMARDs) for moderate to severe disease (Aust Prescr 2003;26:36-40). If these drugs are not effective or not tolerated, biological agents such as tumour necrosis factor (TNF) inhibitors may be considered.
Abatacept, a genetically-engineered protein, is a biological drug for rheumatoid arthritis which is designed to suppress T cell-mediated inflammatory reactions. It is made up of the extra cellular part of the human cytotoxic lymphocyte-associated antigen (CTLA-4) linked to a fragment of human immunoglobulin G. Abatacept works by binding to two signal molecules (CD80 and CD86) on antigen-presenting cells, thereby preventing them from activating T cells.
Abatacept should be given as a 30 minute intravenous infusion. The dose is dependent on the patient's body weight. The infusion should be repeated at two and four weeks and then every four weeks after that. Following multiple 10 mg/kg intravenous infusions of abatacept, the serum concentration reaches a steady state after 60 days. The mean half-life is approximately 13 days in patients with rheumatoid arthritis, and clearance increases with body weight.
When given as a monotherapy to patients with severe active rheumatoid arthritis, more patients responded to abatacept (10 mg/kg) than to placebo. After 85 days, a 20% clinical improvement (based on the criteria of the American College of Rheumatology) was observed in 53% of patients on abatacept compared with 31% on placebo.1 This study was primarily a dose-finding trial and so there were only 32 patients in the abatacept 10 mg/kg group.
Abatacept appears to be efficacious when given in combination with other DMARDs.23456 In a trial of patients with active disease despite methotrexate, 652 patients were randomised to also receive abatacept or placebo. After a year, 73% of patients given abatacept had a 20% clinical improvement compared to only 40% of those given placebo. There was slower radiological progression of joint damage in the abatacept group.4
In another trial patients who had not responded to anti-TNF therapy received either abatacept or placebo with another DMARD. More patients in the abatacept group than in the control group had a 20% improvement (50% vs 20% of patients after six months). However, reduced progression of joint damage was not established in these patients.5
Infusion-related reactions, such as dizziness and headache, are common with abatacept. In a one-year safety trial of 1441 patients, serious infections were more frequent with abatacept than with placebo (2.9% vs 1.9%). Pneumonia was the most common type of serious infection. In patients receiving other biological drugs as well as abatacept, the rate of serious infections increased to 5.8%. Overall, the incidence of neoplasms was similar with abatacept compared to placebo (3.5%). However, this rate increased to 6.8% in patients who were also taking other biological drugs. In patients with chronic obstructive pulmonary disease, there were more adverse events with abatacept than with placebo.7
As abatacept inhibits T cell activation, it may affect a patient's ability to fight infections or malignancies. Caution is needed when treating patients who have a history of recurrent infections and patients should be checked for latent tuberculosis infections and viral hepatitis before starting treatment. Live vaccines should be avoided.
Abatacept in combination with methotrexate is indicated for patients with moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to other DMARDs. Non-biological DMARDs can be used with abatacept, however, it should not be given with biological drugs such as adalimumab, anakinra, etanercept and infliximab.
As rare but potentially fatal adverse effects can occur with abatacept, longer-term safety studies are needed. It is not known how abatacept compares with other treatments for rheumatoid arthritis as there do not appear to be any comparative studies.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the website of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.eu).
- Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum 2002;46:1470-9.
- Kremer JM, Dougados M, Emery P, Durez P, Sibilia J, Shergy W, et al. Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase IIb, double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:2263-71.
- Emery P, Kosinski M, Li T, Martin M, William GR, Becker JC, et al. Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life. J Rheumatol 2006;33:681-9.
- Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis. Ann Intern Med 2006;144:865-76.
- Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor Î± inhibition. N Engl J Med 2005;353:1114-23.
- Westhovens R, Cole JC, Li T, Martin M, Maclean R, Lin P, et al. Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multi centre randomized clinical trial. Rheumatology 2006;45:1238-46.
- Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs. Arthritis Rheum 2006;54:2807-16.