REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis

Abstract

INTRODUCTION:We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC).METHODS:REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult outpatients with UC treated with tofacitinib. The primary outcomes were achievement of clinical and endoscopic remission. Safety outcomes were reported using incidence rates (events/100 patient-years of exposure). A multivariable Cox proportional hazards model was used to evaluate predictors of loss of response after tofacitinib dose de-escalation to 5 mg twice daily (BID).RESULTS:Clinical remission was achieved by 35.3% (106/300), 36.0% (104/289), and 35.2% (93/264) of patients at weeks 12, 24, and 52, respectively. Endoscopic remission was achieved by 18.5% (15/81), 23.0% (28/122), and 25.7% (35/136) of patients at weeks 12, 24, and 52, respectively. Incidence of serious infections, herpes zoster, and venous thromboembolism were 2.1 [0.9–4.2], 0.5 [0.1–1.9], and 1.1 [0.3–2.7], respectively. Among responders, 44.5% (109/245) lost response during follow-up, which was recaptured in 54.9% (39/71) of patients who re-escalated to 10 mg BID. Patients with a baseline Mayo endoscopic score of 3 (adjusted hazard ratio 3.60 [95% confidence interval: 1.70–7.62]) and prior biologic failure (adjusted hazard ratio 3.89 [95% confidence interval: 1.28–11.86]) were at a higher risk for losing response after dose reduction.DISCUSSION:One-third of patients with UC treated with tofacitinib achieved clinical remission with few serious adverse events. However, half of patients lost response with de-escalation, which was only partially recaptured with increasing the maintenance dose. Those with negative prognostic factors should be counselled about the risks and benefits of continuing high doses of tofacitinib.

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry

“…Similar to previous studies, no compelling predictors for long-term treatment success could be detected in the TOUR ( 20 , 21 ). We found a statistically significant association between lack of steroids at week 8 and response or remission at week 52, but no association was found with lack of steroids at week 12 and response or remission at week 8.…”

“…In TOUR, approximately one-fifth of patients were fully vaccinated at the start of tofacitinib therapy; the vaccination rates increased over time to slightly above 50%. This vaccination rate is still significantly below the 80% vaccination rate reported in the Canadian Real-World REMIT-UC study ( 20 ). However, in the Canadian study, vaccination data were unavailable for roughly 30% of the included patients, and thus, the real vaccination rate may have been overreported.…”

“…The later published real-world effectiveness and safety of tofacitinib for moderate-to-severely active ulcerative colitis (REMIT-UC) study, a retrospective study with the largest patient population of 375 patients in Canada, was not included in the abovementioned meta-analysis. REMIT-UC reported remission rates of approximately 35% between weeks 12 and 52 and response rates similar to the reported proportions of patients in response with mild or no disease activity in the TOUR of 64% at week 12 (TOUR: 60%), 50% at week 24 (TOUR: 50% week 20), and 45% at week 52 (TOUR: 43%) ( 20 ). Due to the prospective approach of TOUR, we could additionally reliably assess steroid-free remission rates, which were slightly lower (−8.7% week 12, −3.9% week 20, and −3.9% week 52) but in the same range as the overall remission rates, indicating the robust efficacy of tofacitinib in patients responding to this drug.…”

“…Only 15% of TOUR patients de-escalated tofacitinib in the maintenance period, and most of them failed the lower dose and had re-escalated to the higher dose again or switched out of class. Dose reductions in other real-world studies occurred in more than 60%–70% of patients (Canada, UK, Spain) ( 20 , 26 , 27 ). The low de-escalation rate in the TOUR seems counterintuitive to the recent US FDA and EMA recommendations.…”

“…This trial demonstrated that patients with more severe endoscopic inflammation and previous failure of anti-TNF therapy harbor a significantly higher risk of relapse on lower doses of tofacitinib ( 28 ). The severity of endoscopic inflammation and previous exposure to anti-TNF have also been identified as risk factors of losing response to lower doses of tofacitinib by the real-world Canadian REMIT-UC study ( 20 ).…”