Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

Sankalp Virendrakumar Bhavsar; Mohammad Movahedi; Angela Cesta; Janet E Pope; Claire Bombardier; other OBRI investigators

doi:10.1016/j.jbspin.2024.105732

Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

Joint Bone Spine. 2024 Apr 5;91(4):105732. doi: 10.1016/j.jbspin.2024.105732. Online ahead of print.

Authors

Sankalp Virendrakumar Bhavsar¹, Mohammad Movahedi², Angela Cesta³, Janet E Pope⁴, Claire Bombardier⁵; other OBRI investigators

Affiliations

¹ 407-672, Brant Street, Burlington, Ontario, ON, Canada.
² Ontario Best Practices Research Initiative (OBRI), Toronto General Research Institute University Health Network, Toronto, Canada; Institute of Health Policy, Management, and Evaluation (IHPME), University of Toronto, Toronto, Canada. Electronic address: Mohammad.Movahedi@uhn.ca.
³ Ontario Best Practices Research Initiative (OBRI), Toronto General Research Institute University Health Network, Toronto, Canada.
⁴ Saint-Joseph's Health Care, 268, Grosvenor St, London, ON, Canada.
⁵ Ontario Best Practices Research Initiative (OBRI), Toronto General Research Institute University Health Network, Toronto, Canada; Institute of Health Policy, Management, and Evaluation (IHPME), University of Toronto, Toronto, Canada.

PMID: 38583692
DOI: 10.1016/j.jbspin.2024.105732

Abstract

Objective: There are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations.

Methods: Patients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined.

Results: Six hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2-21.2) compared to double therapy (9.6 months; 95%CI: 7.03-12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005).

Conclusion: Patients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Keywords: Discontinuation; Disease activity; Real-world data; Retention; Rheumatoid arthritis; csDMARDs.