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Real‐World Outcomes Associated With Methotrexate, Sulfasalazine, and Hydroxychloroquine Triple Therapy Versus Tumor Necrosis Factor Inhibitor/Methotrexate Combination Therapy in Patients With Rheumatoid Arthritis
Author(s) -
Curtis Jeffrey R.,
Palmer J. Lynn,
Reed George W.,
Greenberg Jeffrey,
Pappas Dimitrios A.,
Harrold Leslie R.,
Kremer Joel M.
Publication year - 2021
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.24253
Subject(s) - medicine , hydroxychloroquine , rheumatoid arthritis , combination therapy , discontinuation , sulfasalazine , methotrexate , hazard ratio , etanercept , oncology , disease , confidence interval , covid-19 , ulcerative colitis , infectious disease (medical specialty)
Objective Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real‐world experiences comparing these strategies have not been well studied. Methods We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics‐naive or biologics‐exposed status of study participants. Results Patients eligible for analysis in this study included biologics‐naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics‐exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93–98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63–2.88] in the biologics‐naive group; adjusted HR of 1.51 [95% confidence interval 1.06–2.15] in the biologics‐exposed group). At 6 months, the proportion of biologics‐naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (–9.3 units versus –5.5 [95% confidence interval –1.5, –6.1]). Corresponding results in the biologics‐exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. Conclusion Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.