How well does adalimumab work to treat rheumatoid arthritis and how safe is it?
To answer this question, scientists analyzed six high quality studies. The studies tested over 2300 people who had rheumatoid arthritis for more than 10 years. People had either injections of adalimumab or fake injections. Some studies also tested people taking methotrexate in combination with adalimumab or the fake injections. This Cochrane Review provides the best evidence we have today.
What is rheumatoid arthritis and how can adalimumab help?
Rheumatoid arthritis is a disease in which the body's immune system attacks its own healthy tissues. The attack happens mostly in the joints of the feet and hands and causes redness, pain, swelling, and heat around the affected joints. Adalimumab is a "biologic" that is injected into the body to decrease pain and swelling and slow the progress of rheumatoid arthritis. Adalimumab is a new drug that was approved for injection at a dose of 40 mg every other week. It is usually prescribed when other disease modifying anti-rheumatic drugs (DMARDs) do not work well.
How well did adalimumab work?
More people improved with all doses of adalimumab plus methotrexate than with fake injections plus methotrexate. After 24 weeks:
- 43 out of 100 people showed a 50% improvement with 40 mg of adalimumab every other week plus methotrexate
- 9 out of 100 people showed a 50% improvement with fake injections plus methotrexate
This means that 34 more people out of 100 benefited from receiving adalimumab plus methotrexate than fake injections plus methotrexate.
More people had improved symptoms with adalimumab alone than with fake injections, but the improvement was not at much as when adalimumab was taken in combination with methotrexate.
After 52 weeks, x-rays showed that 20 mg of adalimumab every week or 40 mg every other week slowed joint damage more than fake injections.
Were there any side effects?
Minor side effects included reactions where the needle was injected, headaches, allergy-like symptoms, and colds. Some people went to hospital because of serious side effects. Most side effects occurred about the same amount for people taking adalimumab and people taking fake injections.
- 5 out of 100 people had serious side effects with 40 mg of adalimumab every other week plus methotrexate
- 7 out of 100 people had serious side effects with fake injections plus methotrexate
This means that 2 more people out of 100 had a serious side effect from receiving fake injections plus methotrexate than adalimumab plus methotrexate.
One study showed that people who received adalimumab had more serious infections such as tuberculosis and cancer than people who took fake injections. Long-term side effects still need to be studied.
What is the bottom line?
There is "Gold" level evidence (www.cochranemsk.org) that in people with long-standing rheumatoid arthritis who do not respond to DMARDs, adalimumab at 40 mg every other week plus methotrexate decreases pain and swelling.
On the basis of the studies reviewed here, adalimumab in combination with methotrexate is efficacious and safe in the treatment of the rheumatoid arthritis. Adalimumab 40 mg sc e.o.w. and 20 mg e.w. slows the radiographic progression at 52 weeks. Adalimumab in combination with DMARDs other than methotrexate is also efficacious and safe, even though data from one only study are available and the number of patients in each group is low. Adalimumab in monotherapy is efficacious and safe in the treatment of the rheumatoid arthritis but the effect size is lower than with combined therapy.
Adalimumab is a fully human anti-TNFalpha monoclonal antibody. Published studies indicate that its use in patients with RA can be effective and safe.
The aim of this review was to assess the efficacy and safety of adalimumab in the treatment of RA.
Electronic databases were searched up to August, 2004: MEDLINE, CINAHL, EBM Reviews (CDSR, ACP Journal Club, DARE and CENTRAL) and Health STAR. Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials. Adalimumab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication.
All randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing adalimumab alone or in combination with DMARDs to placebo or other DMARDs.
Two reviewers independently collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Outcome measures included ACR and EULAR responses, DAS 28 and components of ACR response and radiographic data. Safety data were also included. Continuous data were reported as weighted mean difference (WMD) with 95% confidence interval (95%CI), absolute benefit (AB) and relative difference (RD). Dichotomous outcomes were reported as relative risk (RR) with 95% CI, absolute risk difference (ARD) or risk difference (RDiff) with 95%CI and number needed to treat (NNT) or to harm (NNH). When significant heterogeneity was not found, data were pooled.
Six studies with 2381 patients were included in this review. Two comparisons were done: A. adalimumab subcutaneously (sc) + methotrexate (or DMARDs) versus placebo sc + methotrexate (or DMARDs). B. adalimumab sc in monotherapy versus placebo sc. In the comparison A, with adalimumab 40 mg every other week (e.o.w.), the RR to achieve an ACR 20 response at 24 weeks ranged in the included studies from 1.52 to 4.63, and the NNT ranged from 1.9 to 5.4. The RR (95%CI) to achieve an ACR 50 response was 4.63 (3.04-7.05), and the NNT was 3.0 (95%CI 2.0-6.0). The RR (95%CI) to achieve an ACR 70 response was 5.14 (3.14-8.41) and the number needed to treat was 7.0 (95%CI 5.0-13.0). At 52 weeks, the RRs (95%CI) to achieve an ACR 20, 50, and 70 response were 2.46 (1.87-3.22), 4.37 (2.77-6.91), and 5.15 (2.60-10.22), with NNTs of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg e.o.w. and 20 mg every week (e.w.) significantly slowed the radiological progression including Sharp modified index, erosion score, and joint space score (only with 40 mg e.o.w.). In the comparison B, with adalimumab 40 mg e.o w. , the RRs to achieve an ACR 20, 50, and 70 response at 24/26 weeks were 1.91 (1.17-3.10), 2.84 (1.58-5.12), and 7.33 (2.25-33.90) with NNTs of 5.0 (95%CI 3.0-9.0), 7.0 (4.0-20.0), and 9.0 (3.0-38.0), respectively. In most of the analysed studies and comparisons, there were not significant differences in safety outcomes between adalimumab and control groups. The development of positive antinuclear antibodies was significantly more frequent in adalimumab patients than in placebo patients. Serious infections were significantly more frequent in adalimumab patients in only one study (Keystone 2004) with a RR (95%CI) of 7.64(1.02-57.18) and a NNH of 30.2.