Tofacitinib Persistence in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study

Abstract

Objective To compare medication persistence of tofacitinib with persistence of injectable biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA). Methods We performed a retrospective new-user cohort study of patients with RA in the IBM MarketScan Research Databases. New users of tofacitinib or bDMARD were identified between November 2012 and December 2016. Persistence, in number of years, was the time between treatment initiation and the earliest occurrence of discontinuation or switching from the medication prescribed at cohort entry. Persistence of tofacitinib was compared with bDMARD persistence using Cox proportional hazards regression with adjustment for high-dimensional propensity scores. Similar methods were used for an analysis of post first‑line therapy in patients who switched to tofacitinib from a bDMARD. Results New tofacitinib users (n = 1031) were 56 years of age, on average, and 82% were women. New bDMARD users (n = 17,803) were 53 years of age, on average, and 78% were women. New tofacitinib users had shorter medication persistence (median 0.81 yrs) compared to bDMARD patients (1.02 yrs). After adjustment, the HR for discontinuation of tofacitinib compared with bDMARD was 1.14 (95% CI 1.05–1.25). Patients who switched to tofacitinib from a bDMARD had longer persistence than patients who switched to a bDMARD (adjusted HR for discontinuation 0.90, 95% CI 0.83–0.97). Conclusion Further research is warranted to understand the reasons for discontinuation of tofacitinib despite its ease of administration and to understand the observed differences between switchers and new users.

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

“… 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.…”

“…A Canadian study of IBM MarketScan Research databases with data from the US found that new tofacitinib users (n = 1031) had shorter medication persistence compared to new bDMARD patients (n = 17,803). 21 Median persistence was 0.81 vs 1.02 years, respectively, and the adjusted hazard ratio (HR) for discontinuation of tofacitinib compared with bDMARDs was 1.14 (95% CI: 1.05–1.25). However, patients who switched from a bDMARD to tofacitinib had longer persistence than those who switched from one bDMARD to another agent: adjusted HR for discontinuation was 0.90 (95% CI: 0.83–0.97).…”

“…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%).…”

Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis (RA): A Retrospective Study From Two Centers in Jeddah, Saudi Arabia

“…Tofacitinib is a JAK inhibitor intended for the treatment of moderately to severely active RA in adults who failed or are intolerant to csDMARDs [3]. Tofacitinib, an orally administered small molecule, may provide a convenient benefit over injectable bDMARDs [4]. Clinical trials have demonstrated that tofacitinib, either as monotherapy or in conjunction with csDMARDs, is able to considerably reduce disease activity as measured by the American College of Rheumatology (ACR) response rates, the EULAR responses and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores [5].…”

Real-world Evidence Needs Careful Interpretation

“…In this issue of The Journal, Fisher, et al 5 have examined the persistence of JAK1/3 inhibitor tofacitinib in patients with RA compared to the persistence of bDMARD of a large, carefully performed, retrospective new user cohort study in a large Canadian MarketScan research database. Over a 4-year period, new users were compared and the time between treatment initiation to discontinuation or drug switch was determined.…”