A 48‐week, randomized, double‐blind, double‐observer, placebo‐controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: Results of the METGO study

Abstract

Objective. To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX).Methods. A randomized, double-blind, doubleobserver, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy.Results. Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo ( 2 ‫؍‬ 6.04, P ‫؍‬ 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P ‫؍‬ 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P ‫؍‬ 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P ‫؍‬ 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P ‫؍‬ 0.022) due to loss to followup, adverse events, or lack of efficacy.Conclusion. In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.Rheumatoid arthritis (RA) affects ϳ1% of North Americans, with profound impact on their quality of life (1) as well as economic consequences for them, their

American College of Rheumatology Clinical Trial Priorities and Design Conference, July 22–23, 2010

“…Trials that have randomly assigned this group of patients (suboptimal responders to MTX) have shown at least 13 different clinically available therapies that are effective. Successful therapies have included cyclosporine (8), sulfasalazine and hydroxychloroquine (9), leflunomide (10), gold (11), all the currently available TNF inhibitors (12)(13)(14)(15)(16), anakinra (17), rituximab (18), abatacept (19), and tocilizumab (20). Despite this plethora of data, there has only been 1 reported study of a single-blind trial that compared active biologic therapies to each other-infliximab versus abatacept (21).…”

“…Clinical trials that simply show that a new therapy is better than a placebo when proven effective therapies are available for that particular clinical situation are of limited utility and should be discouraged. Patients with disease that remains active despite treatment with MTX (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and those with disease that remains active despite treatment with MTX and at least 1 TNF inhibitor (1-4) as noted above are prime examples. In the group with disease that remains active despite treatment with MTX, more than a dozen different therapies have been shown to be effective, yet only a single-blind clinical trial has compared active therapies in this common clinical situation (21).…”

Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews

“…The overall OR for withdrawal with combination therapy was 1.51 (95% CI 1.02 to 2.25). Seven 66,67,222,223,225,227,229 of these studies used methotrexate as the monotherapy arm; the OR for withdrawal was 1.58 (95% CI 0.97 to 2.59).…”

“…[224][225][226][227]229 Only three of these trials reported both mean changes and SDs for these changes. [224][225][226] A combined analysis of these three trials' HAQ scores (see Table 45) showed that, overall, there were greater improvements with cDMARDs than with DMARD monotherapy (WMD −0.19, 95% CI −0.27 to −0.10).…”

The Anti-rheumatic Gold Salt Aurothiomalate Suppresses Interleukin-1β-induced Hyaluronan Accumulation by Blocking HAS1 Transcription and by Acting as a COX-2 Transcriptional Repressor

“…In 1929, Forestier (believing that RA was related to tuberculosis) was the first to pioneer the use of gold injections as a treatment for RA (20). Despite their many side effects, gold compounds are still in use today and, as demonstrated again by a very recent report (21), can indeed be of great benefit for RA patients.…”