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.
Humira (Abbott Australia)
vials/pre-filled syringes containing 40 mg solution
Approved indication: rheumatoid arthritis
Australian Medicines Handbook section 15.2.1
Modern treatment for rheumatoid arthritis aims to modify the disease process with drugs such as methotrexate.1 In some patients treatment with disease-modifying drugs is unsuccessful and biological agents such as the inhibitors of tumour necrosis factor alpha (TNF-α) may be needed.2
Adalimumab is a genetically engineered antibody. It is a 'humanised' antibody as its gene sequence is not derived from animals. Adalimumab binds to TNF-α preventing it from acting on receptors on the surface of cells. This blocks the inflammatory process and results in a rapid fall in the erythrocyte sedimentation rate and concentrations of C-reactive protein.
Although adalimumab only needs to be administered once every two weeks, it has to be injected. After subcutaneous injection it takes five days to reach the peak serum concentration. These concentrations are higher than the concentration in synovial fluid. Serum concentrations are increased if the patient is also taking methotrexate.
Significantly more patients respond to adalimumab than to placebo. After 26 weeks 46% of patients will have had a 20% improvement compared to 19% of those given a placebo. A study of 36 patients who took adalimumab for two years found that there was no radiological progression of the arthritis in 15.3
Adalimumab has also been studied in combination with methotrexate. After 24 weeks there was a 20% improvement in 45 of the 67 patients taking methotrexate and adalimumab 40 mg. Only 9 of the 62 patients who took methotrexate and a placebo had a similar response.4
As adalimumab has an immunosuppressant effect there is a risk of serious infection. Patients should be checked for latent tuberculosis before they start treatment. Caution is also needed if the patient has a demyelinating disease. Antibodies to adalimumab can develop during treatment and this tends to reduce the therapeutic response. Some patients experience hypersensitivity reactions.
During clinical trials 6.6% of patients discontinued treatment with adalimumab because of adverse effects. Common adverse effects include injection site reactions, dizziness and infections. Treatment may reduce haemoglobin and increase lipid concentrations.
Although a 20% improvement was the outcome used to establish efficacy in trials4 , patients may not notice much change. Less than one patient in four will experience a 70% improvement in their arthritis while taking methotrexate and adalimumab. Currently, there is limited information whether the modest benefits seen in the trials will translate into long-term prevention of disability. There is also concern that long-term inhibition of TNF-α could increase the risk of autoimmune diseases or cancer.
There are no direct comparisons of adalimumab with the other TNF-α inhibitors. A meta-analysis suggests that no product is clearly more efficacious than the others.5
* At the time the comment was prepared, information about this drug was available on the web site 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.europa.eu).
- Lee A, Pile K. Disease modifying drugs in adult rheumatoid arthritis. Aust Prescr 2003;26:36-40.
- McColl G. Tumour necrosis factor alpha inhibitors for the treatment of adult rheumatoid arthritis. Aust Prescr 2004;27:43-6.
- den Broeder AA, Joosten LA, Saxne T, Heinegard D, Fenner H, Miltenberg AM et al. Long term anti-tumour necrosis factor α monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis 2002;61:311-8.
- Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate. Arthritis Rheum 2003;48:35-45.
- Hochberg MC, Tracy JK, Hawkins-Holt M, Flores RH. Comparison of the efficacy of the tumour necrosis factor alpha blocking agents adalimumab, etanercept and infliximab when added to methotrexate in patients with active rheumatoid arthritis. Ann Rheum Dis 2003;62(Suppl 2):II13-6.