Triple Therapy Versus TNFi Plus Methotrexate for Rheumatoid Arthritis: A Real-World Treatment Comparison

A recent study compared real-world outcomes between rheumatoid arthritis (RA) patients treated with triple therapy versus tumor necrosis factor inhibitor (TNFi) plus methotrexate (TNF/MTX). The researchers concluded that Triple therapy is not nearly as common as TNF/MTX and may not be as clinically effective.

“Despite randomized controlled trials showing relatively comparable clinical outcomes with triple therapy (Triple; MTX [methotrexate], SSZ [sulfasalazine], HCQ [hydroxychloroquine]) vs combination therapy with TNFi+MTX (TNF/MTX), the real‐world experience comparing these strategies has not been well studied,” the study authors observed.

RA patients in the Corrona registry were propensity score-matched and compared based on their therapy regimen. They were stratified by biologic-naïve versus biologic-experienced.

In the biologic-naïve group, there were 3,926 TNF/MTX patients and 262 Triple patients. In the biologic-experienced group, there were 3,365 and 130 patients, respectively. Prior to propensity score matching, the patient groups were not balanced in that Triple patients were more likely to be older and have longer RA disease duration, lower RA disease activity, and a history of malignancy and other comorbidities. After performing matching, between 93% and 98% of these patients were successfully matched to TNF/MTX patients.

Triple patients, compared to TNF/MTX patients, were more likely to discontinue therapy in both the biologic-naïve (adjusted odds ratio [aHR]=2.17; 95% confidence interval [CI], 1.63 to 2.88) and biologic-experienced groups (aHR=1.51; 95% CI, 1.06 to 2.15). After six months, in the biologic-naïve group, TNF/MTX patients had a significantly greater proportion of patients attain low disease activity compared to the Triple group (49.2% vs. 33.3%); biologic-naïve TNF/MTX patients also had a significantly greater mean change in Clinical Disease Activity Index (–9.3 units vs. –5.5 units; 95% CI, –1.5 to –6.1). Similar results were observed in the biologic-experienced cohort, but the difference was not as significant.

The study was published in Arthritis Care & Research.

“Few patients receive Triple in the US. Drug persistence and clinical effectiveness outcomes were less favorable for Triple compared to TNF/MTX therapy,” summarized the authors.