Anti-Tumor Necrosis Factor-α Therapy of Rheumatoid Arthritis

Abstract

Publisher Summary This chapter summarizes the rationale for anti-tumor necrosis factor-α (anti-TNFα) antibody therapy and its clinical effects, which have been remarkably reproducible, albeit temporary. With this resource of clinical samples and observations on rheumatoid arthritis (RA) patients who transiently but markedly improve, we have had a novel opportunity to unravel the pathogenesis of RA. Like all new therapeutic ventures, much remains to be learned about the optimal use of anti-TNFα therapy and about its limitations and possible pitfalls. To date, the results in RA are highly encouraging, and the benefits of anti-TNFα therapy have rapidly been extended to Crohn's disease. The chapter explores the validation of the proposal that TNFα is a good therapeutic target in RA. Clinical benefit is repeatedly observed during subsequent infusions leading to the conclusion that, unlike cancer, the molecular mechanism of RA—that is, its TNFα dependence, cannot alter. The effectiveness of anti-TNFα therapy in RA is also be helpful in refining the design of clinical trials, in defining and validating criteria of benefit, and in developing surrogate markers for clinical efficacy. This encouragement has stimulated the reevaluation of mechanisms of action of existing drugs and the search for new drugs that mimic the specificity and efficacy of anti-TNF.