Combination Therapy v. Triple Therapy in RA


Rheumatoid arthritis patients seem to embrace combination therapy over triple therapy, a new study shows.

In an analysis of claims data for U.S. Veteran patients with rheumatoid arthritis, treatment with a combination of TNFi therapy and methotrexate, was associated with a significant difference in treatment adherence as compared to triple therapy with three DMARDs.

The findings are significant, in part, because it has been well documented that greater adherence to prescribed therapeutics is associated with better clinical outcomes.

Published in the June 6 online issue of Arthritis Care and Research, researchers compared the adherence to triple therapy with non-biologic disease-modifying anti-rheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine and sulfasalazine, to a tumor necrosis factor inhibitor plus MTX (TNFi+MTX) in patients with rheumatoid arthritis (RA).

The study, which was led by Brian Sauer, Ph.D., of the University of Utah, is based on the analysis of data from U.S. veterans with rheumatoid arthritis who began combination therapy or triple therapy between January 2006 and December 2012. It ultimately included 4,364 patients (3,204 were prescribed TNFi and MTX; and, 1,160 were prescribed triple therapy).  [[{"type":"media","view_mode":"media_crop","fid":"49265","attributes":{"alt":"©Burlingham/","class":"media-image media-image-right","id":"media_crop_7766573897685","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5929","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©Burlingham/","typeof":"foaf:Image"}}]]

Treatment persistence after one year was defined in three ways:  (1) no gap in therapy of at least 90 days for any drug in the original combination (2) no added or switched DMARD, no decrease to nonbiologic DMARD monotherapy and no termination of all DMARD therapies and (3) finally, the third definition was similar to the second, however it allowed a switch to another drug within the same class.

Researchers found that patients in the TNFi+MTX group were significantly more likely than patients in the triple therapy group to satisfy all persistence criteria in Definition 1 (risk difference [RD]: 13.1%; 95% confidence interval [CI]: 9.2%, 17.0%), Definition 2 (RD: 6.4%; 95% CI: 2.3%, 10.5%), and Definition 3 (RD: 9.5%; 95% CI: 5.5%, 13.6%). Patients in the TNFi+MTX group also exhibited higher adherence during the first year (RD: 7.2%; 95% CI: 3.8%, 10.5%).

Three clinical trials have compared triple therapy (MTX+hydroxychloroquine+sulfasalazine) to the combination therapy TNFi+MTX in patients with RA. One study showed that combination had better outcomes than triple therapy, but two showed a similar efficacy between the two groups. Researchers cited another analysis in which less than one-third of patients were persistent or adhered to triple therapy or etanercept-MTX combination therapy. A previous study also showed that triple therapy users had significantly lower odds of being persistent or adherent than users of 2-drug biologic combination therapy.



The study was funded by Amgen Inc. with supplemental funding provided by a Veterans Affairs Health Services Research and Development Award. The authors disclosed a number of conflicts of interest.



Brian C. Sauer, Chia-Chen Teng, et al.

"Persistence With Conventional Triple Therapy Versus a Tumor Necrosis Factor Inhibitor and Methotrexate in U.S. Veterans With Rheumatoid Arthritis,"

Arthritis Care & Research

. DOI 10.1002/acr.22944 Published onlineL  June 6, 2016.



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