Have traditional DMARDs had their day? Effectiveness of parenteral gold compared to biologic agents

This review tries to answer the question of whether in the face of the recently introduced biologics conventional disease-modifying antirheumatic drugs (DMARDs) can still be recommended in the treatment of rheumatoid arthritis (RA). We start with an overview of the oldest conventional DMARD, injectable gold (Au), which was introduced in the treatment of RA in the 1920s. The effect of gold is directed at a number of different sites of the immune system. A significant improvement of clinical and biochemical disease activity parameters as well as an inhibition of X-ray progression has been shown in many studies. Head-to-head comparisons between gold and high-dose methotrexate (MTX) demonstrated no significant difference but some advantages for gold. Since trials comparing biologics with gold will never be performed, an indirect comparison was done by analyzing the results of trials with gold with those with biologics. Conclusions from such comparisons have to be drawn with caution especially since the methodology for performing trials has changed with time. We selected four trials with gold (two open, one placebo-controlled, and one comparison with MTX) and five trials with biologics (three placebo-controlled, one dose escalation study, and one comparison with MTX). In all these trials baseline data regarding swollen joint count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were roughly comparable and, with the exception of interleukin (IL)-1 RA, demonstrated a similar improvement of over 50% already after 6 months [with faster onset with tumor necrosis factor (TNF)-alpha blockade]. American College of Rheumatology (ACR) response data were not available for the older gold trials. European League Against Rheumatism (EULAR) response criteria could be calculated for the Au/MTX trial and were - for these compounds - only slightly inferior to the results with adalimumab. X-ray response is especially difficult to compare across studies. Although an inhibition with Au and MTX could be demonstrated, this occurred - similar to corticosteroid treatment - earlier and more pronounced with TNF-alpha blockers. We confirm the statement of Weinblatt that the most modern DMARDs do not appear to be much better than the oldest one indicating that conventional DMARDs are not outdated. Therefore, a sufficient trial of conventional DMARDs should precede the introduction of treatment with the very expensive biologics.