Op0211 time to Discontinuation of Tofacitinib and TNF Inhibitors in Rheumatoid Arthritis Patients With and Without Methotrexate: Data From a Rheumatoid Arthritis Cohort

Abstract

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.

Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients

“…Our data showed a good retention rate of baricitinib over 4 years of follow up compared to other cohort and other JAKi's real world data (( Hernández-Cruz et al, 2022 ; Iwamoto et al, 2021 ; Tamura et al, 2018 ; Pope et al, 2020 ; Mori and Ueki, 2019 ; Zengin et al, 2018 ; Bilgin et al, 2020 ; Movahedi et al, 2020 ; Baldi et al, 2023 ), Table 3 ).…”

Tofacitinib: Real-World Data and Treatment Persistence in Rheumatoid Arthritis

“…A Canadian study from the Ontario Best Practices Research Initiative (OBRI) in patients initiating tofacitinib (n = 208) or TNFi (n = 357), reported discontinuation rates of 36% and 29%, respectively, during a mean follow-up of 17.3 months. 22 Discontinuation rates in patients receiving tofacitinib monotherapy or in combination with MTX were similar.…”

“… Adherence in TOF MR vs IR initiators: 12-month ≥ 0.8 PDC: 48.2% vs 37.7% (p=0.001) 12-month ≥ 0.8 MPR: 80.1% vs 69.9% (p=0.0002). Patients with CDAI improvement, TOF MR vs IR: 25.5% vs 22.1% (p=0.73) 12-month mean duration of treatment for TOF MR vs IR: 243.4 vs 235.7 days (p=0.36) Fisher et al 2020 21 Canadian IBM MarketScan Research Databases (November 2012 –December 2016) New TOF users (n=1031); new bDMARD users (n=17,803) Retrospective cohort study Compare medication persistence of TOF vs injectable bDMARDs New TOF users had shorter persistence compared with new bDMARD patients Median persistence: TOF, 0.81 yr; bDMARDs, 1.02 yr. HR for discontinuation of TOF vs bDMARDs = 1.14 (95% CI: 1.05–1.25) Movahedi et al 2020 22 Ontario Best Practices Research Initiative (OBRI) provincial registry, Canada 565 patients initiating TOF (n=208) or TNFi (n=357) Retrospective cohort study Discontinuation rates of TOF in comparison with TNFi, with/without concurrent MTX NA TOF retention in patients with/without MTX was similar Discontinuation rates: TOF, 36% (n=75); TNFi, 29% (n=103) No significant difference in TOF discontinuation in patients with/without MTX (Logrank, p=0.31) Pope et al 2020 23 Canadian eXel programme (2014–2017) 4276 patients Post hoc observational aggregated study Describe characteristics, treatment patterns and persistence in RA patients treated with TOF TOF 5mg BID, n=4092 (95.7%); 5 mg QD, n=184 (4.3%) Increased use of TOF since 2014, especially among bDMARD-naïve/1-prior-bDMARD patients. Median persistence was ∼2 years.…”

“…16 RA patients initiating tofacitinib usually had longer disease duration and had been exposed to longer bDMARDs than patients initiating a bDMARD. Real-world data demonstrate the value of monotherapy with tofacitinib, showing the drug retention rate is not affected when in association with MTX, differently than bDMARDs, 22 and the effectiveness of tofacitinib as monotherapy appears similar to tofacitinib in combination therapy, in contrast to anti-TNF agents. 18 There is growing evidence of the safety of JAK inhibitors in patients with RA.…”

“…Analysis of the Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM-RA) Registry found that drug maintenance in tofacitinib initiators (n = 806) was significantly higher than TNFi initiators (n = 1862) and comparable with non-TNFi bDMARDs (eg, rituximab, tocilizumab, abatacept) initiators (n = 1355). Median (IQR) drug maintenance was 25 months (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) 1.24) for both non-TNFi bDMARDs and tofacitinib. Discontinuation was most commonly due to ineffectiveness with lower rates for tofacitinib (46%) compared with non-TNFi bDMARDs (50%) and TNFi (57%).…”