People with active rheumatoid arthritis who have a suboptimal response to methotrexate and then switch to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine do just as well and stay on treatment just as long as do those who switch to methotrexate and etanercept, a follow-up study to the RACAT trial shows.
Although evidence shows that patients do well on combination disease-modifying antirheumatic drugs (DMARDs) following methotrexate failure, many rheumatologists still prefer to add a tumor necrosis factor inhibitor such as etanercept, wrote first author Shana M. Peper, MD, of the University of Nebraska, Omaha, and her colleagues (Arthritis Care Res. 2017 Apr 7. doi: 10.1002/acr.23255).
copyright kgtoh/Thinkstock
The observational, follow-up study involved 289 patients with active rheumatoid arthritis with a suboptimal response to methotrexate who had participated in the 48-week, multicenter, double-blind, Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial and then consented to an additional 72 weeks of open-label extended follow-up during which patients and their physicians were free to change or continue treatment. At the end of the double-blind portion, 145 were receiving triple therapy with the conventional DMARDs and 144 were receiving combination therapy with methotrexate and etanercept.
In the RACAT trial, the primary outcome was the 48-week change in 28-joint Disease Activity Score (DAS28). At 24 weeks, patients in both groups who had an inadequate response to their assigned therapy (defined by a change in DAS28 of less than 1.2) were switched to the other treatment arm in a blinded fashion.
After 1 year, 78% of patients on triple therapy remained on it, compared with 63% of patients who began the extended follow-up on the methotrexate-etanercept combination and remained on it.
More patients switched from methotrexate-etanercept to triple therapy than the other way around (P = .005), but when the researchers removed patients who switched at the start of the extended follow-up from the analysis, continuation rates were nearly identical. The results also did not change when the researchers performed analyses using only the patients who did not switch therapy at week 24 during the blinded trial and again with patients assigned to their original randomized groups.
Average DAS28 scores were similar for each group (3.8 ± 1.4 for triple therapy vs. 3.5 ± 1.3 for methotrexate-etanercept) and remained similar at follow-up. There were also no differences between swollen or tender joint counts, patient global health assessments, or erythrocyte sedimentation rates between the groups.
“Triple therapy remained at least as durable and effective as its biologic counterpart,” the authors concluded.
“Our findings suggest that the majority of patients with active disease despite methotrexate respond to triple therapy and will continue to do so with excellent tolerability,” they wrote.
The findings also supported the approach of reserving more costly biologics for patients who continue to have disease progression despite combination conventional DMARD therapy, they added.
The authors reported no relevant funding for the follow-up analysis. One author reported having consulted for Pfizer and received research support from Bristol-Myers Squibb and AstraZeneca. Another author reported having consulted for Medac, Antares, Lilly, Coherus, and GlaxoSmithKline.