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Meta-Analysis
. 2005 Jul 20;2005(3):CD005113.
doi: 10.1002/14651858.CD005113.pub2.

Adalimumab for treating rheumatoid arthritis

F Navarro-Sarabia  1 , R Ariza-Ariza, B Hernandez-Cruz, I Villanueva
Affiliations
Meta-Analysis

Adalimumab for treating rheumatoid arthritis

F Navarro-Sarabia et al. Cochrane Database Syst Rev. .

Abstract

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 Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials.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.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 1 ACR 20.
1.2
1.2. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 2 ACR50.
1.3
1.3. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 3 ACR70.
1.4
1.4. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 4 EULAR response good.
1.5
1.5. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 5 EULAR response moderate.
1.6
1.6. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 6 Withdrawals.
1.7
1.7. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 7 Adverse events (all doses of adalimumab).
1.8
1.8. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 8 Serious adverse events (all doses of Adalimumab).
1.9
1.9. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 9 Withdrawals due to adverse events (all doses of adalimumab).
1.10
1.10. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 10 Infections (all doses of adalimumab).
1.11
1.11. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 11 Serious infections (all doses of Adalimumab).
1.12
1.12. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 12 Tender joints.
1.13
1.13. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 13 Swollen joints.
1.14
1.14. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 14 Patient pain assessment.
1.15
1.15. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 15 Patient global assessment.
1.16
1.16. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 16 Physician global assessment.
1.17
1.17. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 17 HAQ.
1.18
1.18. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 18 CRP.
1.19
1.19. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 19 Modified Sharp Index.
1.20
1.20. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 20 Erosion score.
1.21
1.21. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 21 Joint space index.
1.22
1.22. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 22 ANA (all doses of Adalimumab).
1.23
1.23. Analysis
Comparison 1 Adalimumab s.c + MTX (or DMARDs) versus Placebo s.c +MTX (or DMARDs), Outcome 23 AntiDNA (all doses of adalimumab).
2.1
2.1. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 1 ACR20.
2.2
2.2. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 2 ACR 50.
2.3
2.3. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 3 ACR70.
2.4
2.4. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 4 EULAR response: at least moderate.
2.5
2.5. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 5 EULAR response: good.
2.6
2.6. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 6 Adverse events (all doses of adalimumab).
2.7
2.7. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 7 Serious adverse events (all doses of adalimumab).
2.8
2.8. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 8 Withdrawals due to adverse events (all doses of adalimumab).
2.9
2.9. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 9 Infections.
2.10
2.10. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 10 Serious infections (all doses of adalimumab).
2.11
2.11. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 11 ANA (all doses of adalimumab).
2.12
2.12. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 12 AntiDNA.
2.13
2.13. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 13 DAS28.
2.14
2.14. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 14 Tender joints.
2.15
2.15. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 15 Swollen joints.
2.16
2.16. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 16 Patient pain assessment.
2.17
2.17. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 17 Patient global assessment.
2.18
2.18. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 18 Physician global assessment.
2.19
2.19. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 19 HAQ.
2.20
2.20. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 20 ESR.
2.21
2.21. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 21 CRP.
2.22
2.22. Analysis
Comparison 2 Adalimumab s.c. in monotherapy vs placebo, Outcome 22 Withdrawals.
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Update of

  • doi: 10.1002/14651858.CD005113

References

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