PURPOSE: We systematically compared the efficacy, effectiveness, and safety (adverse events) of abatacept, adalimumab, alefacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, natalizumab, rituximab, tocilizumab, and ustekinumab in patients with rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.
DATA SOURCES: To identify published studies, we searched PubMed, EMBASE, CINAHL, Centre for Reviews and Dissemination, The Cochrane Library, and International Pharmaceutical Abstracts from 2009 (January) to 2011 (October). We also searched the US Food and Drug Administration Center for Drug Evaluation and Research website for additional unpublished data, requested dossiers of information from pharmaceutical manufacturers, and retrieved relevant citations from reference lists of included studies.
REVIEW METHODS: Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to our standard review methods.
RESULTS AND CONCLUSION: Overall, targeted immune modulators are highly effective medications for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis that substantially improve the burden of disease and are generally safe for short-term treatment. For rheumatoid arthritis, low-and moderate-strength evidence indicated that some targeted immune modulators are more efficacious than others. These results were based on three head-to-head trials, several large observational studies, and indirect comparisons of placebo-controlled trials. The evidence is currently insufficient to reliably determine the comparative effectiveness for other indications and in subgroups. Low-strength evidence indicated that serious infections are less common with abatacept than the other drugs and that the rate of adverse events is greater with infliximab than adalimumab or etanercept. Likewise, more patients receiving infliximab withdrew due to adverse events than abatacept, adalimumab, etanercept, and golimumab. Infusion or allergic reactions contributed to the difference in risk.
Targeted immune modulators, commonly referred to as biological response modifiers or simply biologics, are a relatively new category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis. The US Food and Drug Administration approved the first of the biologics (infliximab) in 1998 and approved 9 additional agents since that time for treating various rheumatic conditions and plaque psoriasis: etanercept (1998), anakinra (2001), adalimumab (2002), alefacept (2003), efalizumab (2003), abatacept (2005), rituximab (2006), natalizumab (2008), and certolizumab pegol (2008). In this report, we review the comparative effectiveness, safety, and tolerability of targeted immune modulators.
We systematically compared the efficacy, effectiveness, and safety (adverse events) of abatacept, adalimumab, alefacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, natalizumab, rituximab, tocilizumab, and ustekinumab in patients with rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.
DATA SOURCES:
To identify published studies, we searched PubMed, EMBASE, CINAHL, Centre for Reviews and Dissemination, The Cochrane Library, and International Pharmaceutical Abstracts from 2009 (January) to 2011 (October). We also searched the US Food and Drug Administration Center for Drug Evaluation and Research website for additional unpublished data, requested dossiers of information from pharmaceutical manufacturers, and retrieved relevant citations from reference lists of included studies.
REVIEW METHODS:
Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to our standard review methods.
RESULTS AND CONCLUSION:
Overall, targeted immune modulators are highly effective medications for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis that substantially improve the burden of disease and are generally safe for short-term treatment. For rheumatoid arthritis, low-and moderate-strength evidence indicated that some targeted immune modulators are more efficacious than others. These results were based on three head-to-head trials, several large observational studies, and indirect comparisons of placebo-controlled trials. The evidence is currently insufficient to reliably determine the comparative effectiveness for other indications and in subgroups. Low-strength evidence indicated that serious infections are less common with abatacept than the other drugs and that the rate of adverse events is greater with infliximab than adalimumab or etanercept. Likewise, more patients receiving infliximab withdrew due to adverse events than abatacept, adalimumab, etanercept, and golimumab. Infusion or allergic reactions contributed to the difference in risk.
