Meta‐analysis of the Efficacy and Safety of Adalimumab, Etanercept, and Infliximab for the Treatment of Rheumatoid Arthritis

STUDY OBJECTIVE: To evaluate the efficacy and safety of using the anti-tumor necrosis factor-alpha (anti-TNF-alpha) drugs adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. DESIGN: Systematic review and meta-analysis of 21 randomized, placebo-controlled trials (eight adalimumab, seven infliximab, six etanercept). PATIENTS: Adults with rheumatoid arthritis who received adalimumab (1524 patients), infliximab (1116 patients), etanercept (1029 patients), or placebo (2834 patients) with or without concomitant methotrexate in all groups. MEASUREMENTS AND MAIN RESULTS: A literature search of several databases from January 1995-December 2008 was performed. There were no restrictions based on language or date of publication, and low-quality studies (based on Jadad score) were excluded. American College of Rheumatology (ACR) 20% improvement criteria (ACR20), 50% improvement criteria (ACR50), and 70% improvement criteria (ACR70) were used to compare treatment efficacy. Safety was compared based on frequency of serious adverse events, serious infections, malignancy, and death. Withdrawals due to adverse events and lack of efficacy were also evaluated. With short-term treatment (12-30 wks), etanercept demonstrated the highest risk ratios (RRs) for reaching ACR20 and ACR50: 2.94 (95% confidence interval CI 2.27-3.81) and 5.28 (95% CI 3.12-8.92), respectively. Adalimumab demonstrated the highest RR for achieving ACR70 (5.36, 95% CI 3.76- 7.64). Over a long-term treatment course (1-3 yrs), adalimumab demonstrated the highest RRs (95% CIs) for these parameters: 1.85 (1.07-3.19), 2.80 (1.16-6.77), and 3.23 (1.37-7.61) for ACR20, ACR50, and ACR70, respectively. No statistically significant differences were noted in the safety of any of the three drugs compared with placebo. Infliximab had the highest RRs for withdrawing from the study due to lack of efficacy (2.05, 95% CI 1.33-3.16) and adverse events (0.41, 95% CI 0.18-0.95). CONCLUSION: With short-term treatment, etanercept and adalimumab had higher efficacy results; with long-term treatment, adalimumab appeared to be the most effective. Clinicians should be aware that each of the three drugs has different rates of efficacy and different safety considerations that must be taken into account when selecting the best treatment for an individual with rheumatoid arthritis.