Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). Tofa can be used as an alternative to biologic disease modifying antirheumatic drugs (bDMARDs) including tumor necrosis factor inhibitors (TNFi).Objectives:We aimed to evaluate the discontinuation rate of this drug, with and without concurrent MTX in comparison with TNFi, in patients with RA in the Ontario Best Practices Research Initiative (OBRI).Methods:RA patients enrolled in the OBRI initiating their TOFA or TNFi (adalimumab, certolizumab, etancercept, golimumab, and infliximab) within 30 days prior to or any time after enrolment between 1stJune 2014 (TOFA approval date in Canada) and 31stDec 2018 were included. Time to discontinuation (due to any reason) were assessed using Kaplan-Meier survival (adjusted for propensity score using inverse probability of treatment weight) to compare patients with and without MTX use at initiation of TOFA or TNFi.Results:A total of 565 patients initiated TOFA (n=208) or TNFi (n=357). Of those, 106 (51%) and 222 (62%) were treated with MTX in the TOFA and TNFi group, respectively and mean (SD) disease duration were 13.1 (9.4) and 9.5 (9.4) years. In the TOFA group, 86% were female and mean (SD) age at treatment initation was 60.4 (10.6) years. In the TNFi group 82% were female and mean age (SD) at treatment initation was 57.0 (12.6) years. The TOFA group was more likely to have prior biologic use (61.5%) compared with the TNFi group (31%). At treatment initiation, the mean (SD) clinical disease activcity index was 24.8 (12.1) in the TOFA group and 21.8 (12.0) in the TNFi group.Over a mean of 17.3 month follow-up, discontinuation was reported in 75 (36%) and 103 (29%) of all TOFA and TNFi patients, respectively. After adjusting for propensity score, patients treated with TNFi and MTX remained on treatment longer than those treated without MTX (Logrank p=0.002) while there was no significant difference in TOFA discontinuation in patients with and without MTX (Logrank p=0.31).Conclusion:In this real world data study, we found that TOFA retention is similar in patients with and without MTX, while patients treated with TNFi and MTX remained on treatment longer than those treated without MTX. Merging data with other RA registries in Canada is proposed to increase study power and to provide more robust results.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

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Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment as the first or an alternative option to biologic disease- modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi). The similarity in retention of TNFi and TOFA was previously reported separately by the Ontario Best Practices Research Initiative (OBRI) and the Quebec cohort RHUMADATA®.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TNFi compared to TOFA, using pooled data from both these registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA or TNFi between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Time to discontinuation was assessed using adjusted Kaplan-Meier (KM) survival and Cox regression models. To deal with confounding by indication, we estimated propensity scores for covariates with a standard difference greater than 0.1. Models were then adjusted using stratification and inverse probability of treatment weight (IPTW) methods. Multiple imputation (Imputation by Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Results:A total of 1318 patients initiated TNFi (n=825) or TOFA (n=493) with mean (SD) disease duration of 8.9 (9.3) and 13.0 (10.1) years, respectively. In the TNFi group, 78.8% were female and mean age (SD) at treatment initiation was 57.6 (12.6) years. In the TOFA group, 84.6% were female and mean (SD) age at treatment initiation was 59.5 (11.5) years. The TNFi group was less likely to have prior biologic use (33.9%) than the TOFA group (66.9%). At treatment initiation, the mean (SD) CDAI was significantly (p<0.05) lower in the TNFi group [20.0 (11.7)] compared to the TOFA group [22.1(12.4)]. Physical function measured by HAQ-DI was also significantly lower (p<0.05) in the TNFi compared to the TOFA group (1.2 vs.1.3).Over a mean follow-up of 23.2 months, discontinuation was reported in 309 (37.5%) and 182 (36.9%) of all TNFi and TOFA patients, respectively. After adjusting for propensity score deciles across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 0.96, 95% CI: 0.78-1.18; p=0.69). The results were similar for two propensity adjustment methods. Figure 1 shows IPTW adjusted KM survival curves comparing discontinuation rates in patients treated with TNFi and TOFA.Figure 1.Note: Propensity Score Weighted (IPTW) Survival Curves was performed using one imputed datasetConclusion:In this pooled real -world data study, we found that TNFi and TOFA retention is similar in patients with RA. In the next step we will analysis the data for specific reasons of dicontinutaion. We will also repeat analysis comparing discontinuation in the first users versus those after one or more biologic failure.Disclosure of Interests:Mohammad Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata® is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: None declared, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm. Speaker Honoraria Agreements: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis. Consulting Agreements/Advisory Board Membership: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Claire Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Aurora, Bristol-Meyers Squibb, Celgene, Hospira, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB.Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

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