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ACR Open Rheumatol. 2019 Aug 8;1(8):471-479. doi: 10.1002/acr2.11052. eCollection 2019 Oct.

Joint Estimation of Remission and Response for Methotrexate-Based DMARD Options in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis.

Pokharel G1, Deardon R1, Barnabe C1, Bykerk V2, Bartlett SJ3, Bessette L4, Boire G5, Hitchon CA6, Keystone E7, Pope J8, Schieir O7, Tin D9, Thorne C9, Hazlewood GS1; Canadian Early Arthritis Cohort (CATCH) Investigators, Baron M1,2,3,4,5,6,7,8,9, Bessette L1,2,3,4,5,6,7,8,9, Boire G1,2,3,4,5,6,7,8,9, Bykerk V1,2,3,4,5,6,7,8,9, Colmegna I1,2,3,4,5,6,7,8,9, Fallavollita S1,2,3,4,5,6,7,8,9, Haaland D1,2,3,4,5,6,7,8,9, Haraoui P1,2,3,4,5,6,7,8,9, Hazlewood G1,2,3,4,5,6,7,8,9, Hitchon C1,2,3,4,5,6,7,8,9, Jamal S1,2,3,4,5,6,7,8,9, Joshi R1,2,3,4,5,6,7,8,9, Keystone E1,2,3,4,5,6,7,8,9, Nair B1,2,3,4,5,6,7,8,9, Panopoulos P1,2,3,4,5,6,7,8,9, Penney C1,2,3,4,5,6,7,8,9, Pope J1,2,3,4,5,6,7,8,9, Rubin L1,2,3,4,5,6,7,8,9, Thorne C1,2,3,4,5,6,7,8,9, Villeneuve E1,2,3,4,5,6,7,8,9, Zummer M1,2,3,4,5,6,7,8,9.

Author information

1
University of Calgary Calgary Alberta Canada.
2
Cornell University, New York, New York and Hospital for Special Surgery New York New York.
3
McGill University, Montreal, Quebec, Canada, and Johns Hopkins University Baltimore Maryland.
4
Université Laval Quebec Quebec Canada.
5
Université de Sherbrooke Sherbrooke Quebec Canada.
6
University of Manitoba Winnipeg Manitoba Canada.
7
University of Toronto Toronto Ontario Canada.
8
Western University London Ontario Canada.
9
Southlake Regional Health Center Newmarket Ontario Canada.

Abstract

Objective:

To jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)-based treatment options in rheumatoid arthritis (RA).

Methods:

We conducted a bivariate network meta-analysis (NMA) to compare MTX monotherapy and MTX-based conventional and biologic disease-modifying antirheumatic drug (DMARD) combinations for RA. The correlation between the outcomes was derived from an incident RA cohort study, whereas the treatment effects were derived from randomized trials in the network of evidence. The analyses were conducted separately for MTX-naïve and MTX-inadequate response (IR) populations in a Bayesian framework with uninformative priors.

Results:

From the cohort study, the correlation between ACR50 response and Disease Activity Score 28 remission at 6 months was moderate (Pearson correlation coefficient = 0.58). In the bivariate NMA for MTX-naïve populations, most combinations of MTX with either biologic or tofacitinib were statistically superior to MTX alone for both ACR50 response and remission. Triple therapy (MTX + sulfasalazine + hydroxychloroquine) was the only nonbiologic DMARD statistically superior to MTX for either ACR50 response (odds ratio [OR] 95% credible interval: 2.1 [1.0, 4.3]) or remission (OR: 2.5 [1.0, 5.8]). In the MTX-IR analysis, all treatments except MTX + sulfasalazine were statistically superior to MTX alone. Compared to analyzing the outcomes separately, the bivariate model often resulted in more precise estimates and allowed remission to be estimated for all treatments.

Conclusion:

Borrowing the strength of correlation between outcomes allowed us to demonstrate a statistically significant benefit for remission across most MTX-based DMARD combinations, including triple therapy.

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