Efficacy Including Rapid Response And Safety Of Tofacitinib In Japanese Patients With Ulcerative Colitis: A Preliminary Investigation In A Specialized Ibd Center

Abstract Background Genetic backgrounds and risk of herpes zoster or thrombotic adverse events differ between Western and Asian patients with ulcerative colitis (UC) treated with tofacitinib. We investigated the efficacy and safety of tofacitinib including the rapid response that showed treatment efficacy within ≤4 weeks among Japanese UC patients in our specialised IBD centre. Methods The study included 55 UC patients who were administered tofacitinib 5 or 10 mg twice daily and available for 16 weeks of efficacy and safety examination among 76 patients administered tofacitinib in our hospital. Efficacy was defined as a ≥2-point decrease in partial Mayo score (PMS) from baseline and remission with ≤1 MES coupled with no bloody stool. Results The patients’ age was 38.1±15.0 years, 21 patients were female, duration of disease was 92.7±88.0 months, baseline PMS was 5.2±1.9, white cell count was 7428±2631/µl, C-reactive protein was 1.1±1.7 mg/dl, and serum albumin was 3.9±0.6 g/dl. The last treatment just before tofacitinib administration was steroids (16.4%, 7 cases), anti-TNF agents (29.1%, 17 cases), and vedolizumab (1.8%, 1 case). The efficacy rate was 49.0% (23 cases; rapid responders) at 4 weeks and 74.5% (35 cases) at 16 weeks. Remission rate sequentially increased: 17.0% (8 cases) at 4 weeks, 27.7% (13 cases) at 8 weeks, and 49.0% (23 cases) at 16 weeks. No difference in remission rate was observed between anti-TNF-naïve patients (58.3%) and anti-TNF-treated patients (62.5%; p = 0.84). Additionally, immunomodulatory therapy-naïve patients exhibited a high response rate (80.0%). Moreover, 29.1% patients relapsed during maintenance therapy with 5 mg tofacitinib twice daily after achievement of remission with 10 mg tofacitinib twice daily. Basement PMS was significantly lower in the remission group (4.4 ± 1.7) than in the non-remission group (5.8 ± 1.8) at 16 weeks (p = 0.01). Receiver operating characteristic analysis identified 5.0 of basement PMS as a cut-off value to achieve remission at 16 weeks. Five cases (6.6%) of herpes zoster occurred. All cases were under treatment with tofacitinib 10 mg twice daily and had not been vaccinated. Fortunately, permanent damage was not observed after antiviral therapy. Three cases of fever and one case of leg oedema (as adverse events) recovered rapidly after tofacitinib was withdrawn. No thrombotic adverse event was observed despite the fact that 56.4% patients continued treatment with 10 mg twice daily after 16 weeks. Conclusion Approximately half of the included patients were rapid responders; sequential improvement within 16 weeks was observed. Tofacitinib was more effective in low-activity UC patients; its efficacy was not affected by history of treatment with anti-TNF agents.