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Abstract Number: 604

Combining Observational and Randomized Controlled Trial Data Evidence to Jointly Estimate Remission and Response for Biologic and Non-Biologic Therapies in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis

Gyanendra Pokharel1, Rob Deardon1, Cheryl Barnabe2, Vivian P. Bykerk3, Susan J. Bartlett4, Louis Bessette5, Gilles Boire6, Carol Hitchon7, Edward C. Keystone8, Janet E. Pope9, Diane Tin10, Carter Thorne11 and Glen Hazlewood12, 1Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada, 2Medicine, University of Calgary, Calgary, AB, Canada, 3Hospital for Special Surgery, New York, NY, 4Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 5Division of Rheumatology, Department of Medicine, CHU de Québec-Université Laval, Québec, QC, Canada, 6Rheumatology Division, Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke and Universite de Sherbrooke, Sherbrooke, QC, Canada, 7University of Manitoba, Winnipeg, MB, Canada, 8Mount Sinai Hospital, Toronto, ON, Canada, 9Department of Medicine, University of Western Ontario, London, ON, Canada, 10The Arthritis Program, Southlake Regional Health Centre, Newmarket, ON, Canada, 11University of Toronto, Newmarket, ON, Canada, 12Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Comparative effectiveness and harms, DMARDs, outcomes, rheumatoid arthritis (RA) and treatment

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Session Information

Date: Sunday, October 21, 2018

Session Title: Rheumatoid Arthritis – Treatments Poster I: Strategy and Epidemiology

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Remission is the goal of rheumatoid arthritis (RA) treatment, but ACR responses are more commonly measured in clinical trials. As such, data on remission are lacking for some treatments, or may be imprecise. The objective of this study was to jointly estimate remission and ACR50 responses for methotrexate (MTX)-based treatment options in early RA.

Methods: We conducted a Bayesian bivariate network meta-analysis (NMA) to compare methotrexate monotherapy and methotrexate-based DMARD combinations for RA. The correlation between the outcomes was derived from an observational study (CATCH cohort), whereas the treatment outcomes were derived from randomized trials that formed the connected network of evidence. The analyses were conducted separately for MTX-naïve and MTX-inadequate response populations in a Bayesian framework with uninformative priors. Comparisons were made to a univariate NMA that estimated each outcome separately.

Results: From the incident RA cohort study, the correlation between ACR50 response and DAS28 remission at 6 months was moderate (Pearson correlation coefficient 0.58) for the 900 patients in the CATCH cohort who had moderate-high disease activity at baseline. For MTX-naïve patients, the NMA included 74 trials in total; 39 measured both outcomes, whereas 64 and 49 measured only ACR50 response or remission respectively. Two treatments that were not statistically superior to methotrexate alone for remission in the univariate NMA, were in the bivariate model [Figure 1: bivariate odds ratio (OR) (95% credible interval (CrI)): MTX + infliximab 2.0 (1.2, 3.7), MTX + tofacitinib 2.7 (1.0, 6.2)]. Six treatments had no data for remission in the univariate model, but could be estimated in the bivariate approach. Of these, only triple therapy (MTX + sulphasalazine + hydroxychloroquine) was superior to MTX alone for remission (OR (95%CrI): 2.5 (1.0, 6.1)). In the MTX-IR analysis, all 16 treatments were superior to MTX alone for both ACR50 response and remission in both the univariate and bivariate models, but the CrI were usually more precise in the bivariate approach and remission could be estimated for several treatments not possible in the univariate model, including triple therapy (OR (95%CrI): 17.5 (6.8, 46.1)).

Conclusion: By borrowing the strength across treatments and outcomes, a bivariate NMA allowed the estimation of both ACR50 response and remission for all treatment comparisons. In particular, our results add data on remission for several MTX-based DMARD combinations (including triple therapy and biologic combinations) not demonstrated in the univariate NMA model.


 

../BivariateNMA/Results/MTX-naiveForestPlot.pdf


Disclosure: G. Pokharel, None; R. Deardon, None; C. Barnabe, None; V. P. Bykerk, Amgen Inc., 5,Pfizer, Inc., 5,UCB, Inc., 5,Bristol-Myers Squibb, 5,Sanofi Genzyme, 5,Gilead, 5; S. J. Bartlett, UCB, Inc., 5,Lilly, 5,Pfizer, Inc., 5,Novartis, 5; L. Bessette, Amgen Inc., 2, 5, 8,Bristol-Myers Squibb, 2, 5, 8,Janssen, 2, 5, 8,Roche, 2, 5, 8,UCB, Inc., 2, 5, 8,AbbVie Inc., 2, 5, 8,Pfizer, Inc., 2, 5, 8,Merck & Co., 2, 5, 8,Celgene Corporation, 2, 5, 8,Sanofi, 2, 5, 8,Eli Lilly and Co., 2, 5, 8,Novartis, 2, 5, 8; G. Boire, Merck & Co., 8, 9,BMS, 8, 9,Pfizer, Inc., 8, 9,Amgen Inc., 9,AbbVie Inc., 9,Novartis, 9,Eli Lilly and Co., 9,Janssen, 9; C. Hitchon, Pfizer, Inc., 2; E. C. Keystone, Amgen Inc., 2, 5, 8,Bristol-Myers Squibb, 2,F. Hoffmann-La Roche Inc, 2,Janssen, 2,Lilly Pharmaceuticals, 2,Pfizer Pharmaceuticals, 2,Sanofi-Aventis, 2,AstraZeneca, 5,Biotest, 5,Bristol-Myers Squibb, 5,Crescendo Bioscience, 5,F. Hoffmann-La Roche Inc, 5,Genentech Inc, 5,Janssen Inc, 5,Lilly Pharmaceuticals, 5,Merck & Co., 5, 8,Pfizer Pharmaceuticals, 5,UCB, Inc., 5,Bristol-Myers Squibb, 8,F. Hoffmann-La Roche Inc, 8,Janssen Inc, 8,Pfizer Pharmaceuticals, 8,Sanofi Genzyme, 8,UCB, Inc., 8; J. E. Pope, Amgen Inc., 5, 9,Pfizer, Inc., 5, 9,UCB, Inc., 5, 9,AbbVie Inc., 5,Bristol-Myers Squibb, 5, 9,Actelion, 5,Eli Lilly and Co., 5,Merck & Co., 5, 9,Bayer, 5, 9,Roche, 5, 9,Novartis, 5,Sanofi, 5,Celtrion, 5,Seagen, 9,Genzyme, 5; D. Tin, None; C. Thorne, Amgen Inc., 2, 5, 9,Pfizer, Inc., 2, 5, 9,UCB, Inc., 9,AbbVie Inc., 2, 5, 9,Medexus/Medac, 2, 5, 8,Eli Lilly and Co., 9,Merck & Co., 9,Hospira, 5, 9,Janssen, 9,Sanofi Genzyme, 5, 9,Celgene Corporation, 9,CaREBiodam, 9,Centocor, 5,Novartis, 9; G. Hazlewood, None.

To cite this abstract in AMA style:

Pokharel G, Deardon R, Barnabe C, Bykerk VP, Bartlett SJ, Bessette L, Boire G, Hitchon C, Keystone EC, Pope JE, Tin D, Thorne C, Hazlewood G. Combining Observational and Randomized Controlled Trial Data Evidence to Jointly Estimate Remission and Response for Biologic and Non-Biologic Therapies in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/combining-observational-and-randomized-controlled-trial-data-evidence-to-jointly-estimate-remission-and-response-for-biologic-and-non-biologic-therapies-in-rheumatoid-arthritis-a-bivariate-network-me/. Accessed December 11, 2019.
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