Background Adalimumab is a fully human anti-TNFalpha monoclonal antibody. Published studies indicate that its use in patients with RA can be effective and safe. Objectives The aim of this review was to assess the efficacy and safety of adalimumab in the treatment of RA. Search strategy 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 Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials.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. Selection criteria All randomised controlled trials ( RCTs) or controlled clinical trials ( CCTs) comparing adalimumab alone or in combination with DMARDs to placebo or other DMARDs. Data collection and analysis 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. Main results 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. Authors' conclusions 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.
