EDITORIAL

www.nature.com/clinicalpractice/rheum Are all DMARDs equivalent? Peter E Lipsky

A comprehensive review by Donahue et al. of [These trials] often carried out at a time or place in which rheumatoid arthritis (RA) therapy using disease- … might not the medication might have been perceived modifying antirheumatic drugs (DMARDs) to be the only available therapeutic option, concludes that differences in efficacy among demonstrate which could have artificially bolstered patients’ these agents are difficult to discern (Donahue KE the full compliance. Furthermore, many of the outcome et al. [2008] Ann Intern Med 148: 124–134). spectrum of measures used in clinical trials of RA might lack This finding is not unexpected, considering the variables that a sufficiently large linear range to distinguish general nature of the studies assessed, but it determine differences in effect size between therapeutic could have substantial adverse implications agents with accuracy. Finally, timing of the for the care of patients with RA. The next issue whether or not introduction of therapeutic agents and the use of Nature Clinical Practice Rheumatology will an agent is of objective measures to determine when to present an in-depth analysis of this review by effective alter the treatment regimen might have had an leading experts in the field. important effect on overall outcome, as has The results of Donahue and colleagues’ been demonstrated (Goekoop-Ruiterman YP review are not dissimilar to those of a similar, et al. [2005] Arthritis Rheum 52: 3381–3390). earlier review (Felson DT et al. [1990] Arthritis In view of these considerations, the results Rheum 33: 1449–1461) of the then- available of the review by Donahue et al. are not unex- DMARDS—gold salts, D-penicillamine, pected; their possible implications are, however, sulfasalazine, and methotrexate—in that all of of concern. Biologic DMARDs are very expen- the agents studied showed broadly equivalent sive and, therefore, not widely available or are effects. Time and experience have, however, restricted in their use. We can only hope that indicated that these agents are not inter- the results of the review are not used to restrict changeable; gold salts and D-penicillamine use of biologic DMARDs further because, as are rarely, if ever, used today—most patients are concluded by Donahue et al., “Limited avail- treated with methotrexate, with or without able comparable evidence does not support glucocorticoids. Donahue and colleagues’ one monotherapy over another for adults with review also includes newer chemical DMARDs rheumatoid arthritis”. Data indicating that and agents that neutralize tumor necrosis strategies employing biologic DMARDs can factor, but their conclusions are similar to those be more effective than other approaches are of Felson et al. clearly emerging (Goekoop-Ruiterman YP et al. What could be responsible for the apparent [2005] Arthritis Rheum 52: 3381–3390). The lack of differences in efficacy between rheumatology community must perform DMARDs? First, most of the studies included in the appropriate trials to determine whether the PE Lipsky is the review were carried out by pharma ceutical most frequently used chemical and biologic the Editor-in- companies for the purpose of licensing a Chief of Nature DMARDs and current strategies are indeed product or expanding its indicated uses. As Clinical Practice the most effective for treating patients with these short-term trials include highly selected Rheumatology. RA. A great disservice would be done to indivi- patient populations, they often fail to reflect duals with RA if their therapeutic options were ‘real life’ clinical practice and, consequently, Competing interests restrained by acceptance of the conclusions of The author declared no might not demonstrate the full spectrum of competing interests. a review of trials that were not really designed variables that determine whether or not an to address issues of comparative effectiveness www.nature.com/clinicalpractice agent is effective. Moreover, the trials were doi:10.1038/ncprheum0800 in clinical practice.

MAY 2008 VOL 4 NO 5 NATURE CLINICAL PRACTICE RHEUMATOLOGY 223