Effect of Concomitant Disease-modifying Antirheumatic Drugs and Methotrexate Administration Route on Biologic Treatment Durability in Rheumatoid Arthritis: OBRI Cohort Results.

Authors:
Arthur N Lau
Arthur N Lau
Joseph's Healthcare and McMaster University
Canada
Mohammad Movahedi
Mohammad Movahedi
Shahid Beheshti University of Medical Sciences
Iran
Emmanouil Rampakakis
Emmanouil Rampakakis
McGill University
Canada
Angela Cesta
Angela Cesta
Toronto General Hospital Research Institute
Xiuying Li
Xiuying Li
Shanghai Institute of Materia Medica
China
Sandra Couto
Sandra Couto
Toronto General Hospital Research Institute
Toronto | Canada
John Sampalis
John Sampalis
McGill University
Canada

J Rheumatol 2019 Apr 15. Epub 2019 Apr 15.

From McMaster University, Hamilton, Ontario; Southlake Regional Health Centre, Newmarket, Ontario; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario; JSS Medical Research; McGill University, Montreal, Quebec; University of Toronto, Department of Medicine and Institute of Health Policy, Management, and Evaluation; Mount Sinai Hospital, Division of Rheumatology, Toronto, Ontario, Canada. OBRI was funded by peer-reviewed grants from Canadian Institute for Health Research (CIHR), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN), and unrestricted grants from AbbVie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. MM, AC, XL, SC, and CB are employees at OBRI, which was funded by peer-reviewed grants from CIHR, MOHLTC, CAN, and unrestricted grants from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Hospital Janssen, Pfizer, Roche, Sanofi, and UCB. ER and JSS are employees at JSS Medical Research, a contract research organization. A.N. Lau, MD, McMaster University; J.C. Thorne, MD, Southlake Regional Health Centre; M. Movahedi, MD, PhD, Toronto General Hospital Research Institute, University Health Network; E. Rampakakis, PhD, JSS Medical Research; A. Cesta, BSc, Toronto General Hospital Research Institute, University Health Network; X. Li, BSc, Toronto General Hospital Research Institute, University Health Network; S. Couto, MSc, Toronto General Hospital Research Institute, University Health Network; J. Sampalis, PhD, JSS Medical Research, and McGill University; C. Bombardier, MD, Toronto General Hospital Research Institute, University Health Network, and University of Toronto, Department of Medicine and Institute of Health Policy, Management, and Evaluation, and Mount Sinai Hospital, Division of Rheumatology. Address correspondence to Dr. A.N. Lau, 501-25 Charlton Ave. East, Hamilton, Ontario L8N 1Y2, Canada. E-mail: Accepted for publication October 30, 2018.

Objective: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort.

Methods: Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression.

Results: Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55-1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50-1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24-0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed.

Conclusion: Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.

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http://dx.doi.org/10.3899/jrheum.180486DOI Listing
April 2019
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