Triple therapy inferior to TNF plus methotrexate for persistence, RA disease activity outcomes
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Combination therapy with TNF inhibitors plus methotrexate was significantly superior to triple therapy with methotrexate, hydroxychloroquine and sulfasalazine in patients with rheumatoid arthritis, both in terms of persistence and improved disease activity, according to data published in Arthritis Care & Research.
“Several randomized controlled trials (RCTs) conducted in rheumatoid arthritis (RA) patients have demonstrated that clinical outcomes at two years were comparable, or not significantly different, in rheumatoid arthritis (RA) patients receiving triple therapy (triple) with methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) compared to therapy with TNFi and MTX (TNF/MTX) medications,” Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, and colleagues wrote. “... However, these data sources were limited by a lack of information regarding clinical outcomes (eg, RA disease activity).”
“Also of importance, these and most observational data sources are subject to ‘left censoring’ whereby patients receiving prior treatments for RA might not have this information recorded in the data, such that the ability to study both biologic naive and biologic experienced patients is limited,” they added. “Given that clinical outcomes typically are worse as patients fail an increasing number of RA therapies, the importance of accurately classifying a patient as biologic naive or biologic experienced is therefore quite important.”
To compare triple therapy with combination therapy with TNF inhibitors and methotrexate, in terms of treatment persistence and clinical outcomes, Curtis and colleagues studied data from the Corrona RA registry. According to the researchers, the registry includes information from 373 physicians in 131 sites across 42 states. Focusing on data from 2001 to 2019, the researchers analyzed discontinuation and clinical effectiveness of associated outcomes with triple therapy compared with TNF-inhibitor-plus-methotrexate combination therapy.
The study comprised 3,926 patients treated with TNF inhibitors plus methotrexate and 262 who received triple therapy in the biologic-naive population, and 3,365 patients treated with TNF inhibitors plus methotrexate and 130 patients who received triple therapy in the biologic-experienced population. Curtis and colleagues used propensity score matching to adjust for imbalances, stratifying based on biologic status.
According to the researchers, patients who received triple therapy were older, with longer RA disease duration and lower disease activity. They were also more likely to demonstrate a history of malignancy and other comorbidities compared with patients treated with TNF inhibitors and methotrexate. The researchers were able to match 93% to 98% of patients who received triple therapy to those treated with TNF inhibitors plus methotrexate, with characteristics that were “generally well balanced.”
Curtis and colleagues reported that discontinuation rates were greater among patients treated with triple therapy in both the biologic-naive (adjust HR = 2.17; 95% CI, 1.63-2.88) and biologic-experienced (adjust HR = 1.51; 95% CI, 1.06-2.15) groups.
Among patients who were biologic-naive at 6 months, 49.2% of those treated with TNF inhibitors plus methotrexate achieved low disease activity, compared with 33.3% in the triple therapy group.
“The frequency of the utilization of [triple therapy] in this large U.S. registry covering a wide sample of providers and different sites from 42 different U.S. states was quite low,” Curtis and colleagues wrote. “The baseline characteristics of [triple therapy] vs. TNF/MTX patients showed many meaningful differences; in general, triple therapy users were sicker with comorbidities but had somewhat less active RA. After accounting for these differences through PS matching, biologic naive TNF/MTX patients had superior persistence and clinical effectiveness outcomes compared with Triple patients.”
“These trends were numerically similar in the biologic-experienced population, although the sample size was smaller and not all findings were significant,” they added. “These real-world findings add to our understanding of the choice of [triple therapy] vs. TNF/MTX therapy.” – by Jason Laday
Disclosures: Curtis reports research grants and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche and UCB. Please see the study for all other authors’ relevant financial disclosures.
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