Assessing the safety of biologic therapies in rheumatoid arthritis: The challenges of study design

Clinical trials have shown the anti-tumor necrosis factor-alpha (TNF-alpha) drugs to be safe and efficacious for the treatment of rheumatoid arthritis (RA). However, since their release for general use, reports have raised concerns about potentially serious complications including tuberculosis; lymphoma, and cardiac failure. It must be remembered that patients with RA are already at increased risk of many of these complications,due both to their underlying inflammatory disease activity and the immunosuppressing effects of many conventional disease modifying antirheumatic drugs. It is unknown whether anti-TNF-alpha therapies are putting patients at increased risk of adverse events above what might already be expected. Data on the frequency of these adverse events have come predominantly from 3 sources: followup of subjects recruited to clinical trials, spontaneous adverse event reporting to national pharmacovigilance systems. and surveillance of patients treated in routine practice. Each of these study designs plays an important role in assessment of new drugs. However, each also has limitations, which must be considered when interpreting adverse event rates.