Adding TNF Inhibitors to MTX Superior to Triple Therapy in RA after Inadequate MTX Response

SAN FRANCISCO, CA—Among patients diagnosed with rheumatoid arthritis (RA) that does not adequately respond to methotrexate (MTX), adding tumor necrosis factor inhibitors (TNFi) therapy yields better symptom control than triple therapy (MTX + hydroxychloroquine + sulfasalazine), according to a meta-analysis of randomized controlled trials reported at the 2015 ACR/ARHP Annual Meeting.

“In this network meta-analysis of MTX-IR [methotrexate-inadequate-responding] patients, TNFi-MTX had significantly higher odds than triple therapy in achieving an ACR70 at 6 months,” the primary study end point, lead study author Roy Fleischmann, MD, Rheumatology, Metroplex Clinical Research Center, Dallas, TX, and coauthors reported.

ACR70 represents a 70% improvement in symptoms, based on American College of Rheumatology (ACR) criteria.

“The benefits of TNFi-MTX over triple therapy were shown across clinical and radiographic end points in the MTX-IR population, supporting the use of biological therapy in this setting,” Dr. Fleischmann noted.

Earlier studies did not “convincingly demonstrate” TNFi-MTX to be superior to triple therapy among patients with MTX-inadequate-responder RA, Dr. Fleischmann noted. “This could be due to trials being underpowered to detect true differences,” he noted. “The objective of this study was to estimate the efficacy and radiographic benefits of TNFi-MTX versus triple therapy in MTX-IRs by conducting a systematic review and network meta-analysis. This is an important, clinically relevant question in MTX-IRs.”

To assess whether or not TNFi-MTX is superior to triple therapy for patients with MTX-IR RA, the coauthors searched research journal databases for randomized controlled trials that used either TNFi-MTX or triple therapy as a treatment arm.

End points were analyzed for the 3-month, 6-month, 1-year, and 2-year points from baseline. In addition to the primary end point of ACR70 at 6 months, “other endpoints included ACR20, ACR50, DAS(Disease Activity Score)28 LDA, DAS28 remission, EULAR good response, and no radiographic progression; and changes in DAS28 score, joint erosion, joint space narrowing, and various versions of Sharp scores from baseline,” he noted.

Thirty-nine studies met eligibility criteria, representing a total of 12,749 patients.

“MTX-IRs were significantly less likely to achieve ACR70 with triple therapy than with TNFi-MTX at 6 months in both fixed effects models (FEM) (OR [odds ratio]: 0.35; 95% Credible Interval [CrI]: 0.19, 0.64) and random effects models (REM) (OR: 0.36, 95% CrI: 0.16, 0.80).”

When compared with baseline, except for DAS28 score, all end points demonstrated statistically significant benefits for TNFi-MTX versus triple therapy in FEM—but not REM—at “some point within the 2 years of evaluation from baseline,” he said.

“Across the 54 analyzable endpoint-time scenarios evaluated, 44 numerically favored TNFi-MTX in both FEM and REM,” Dr. Fleischmann concluded.