Tofacitinib induces clinical and endoscopic remission in biologic refractory Ulcerative Colitis patients: A real-world Belgian cohort study

Background
Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNF and vedolizumab.
Methods
This is an observational, national, retrospective multicenter study including all UC active patients started on tofacitinib (10 mg BID) from 25 centers in Belgium between November 2018 to August 2019. Prospectively collected data were retrospectively analyzed according intention-to-treat. Primary endpoints were clinical and endoscopic response and remission rates at weeks 8 and 16. Clinical response and remission were defined as a reduction in Modified Clinical Mayo score (rectal bleeding, stool frequency) of ≥2 and ≤1, respectively. Endoscopic response and remission were defined as a reduction in Endoscopic Mayo score of ≥1 and ≤1, respectively. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed rank test were calculated using Medcal 19.1.
Results
Demographic and baseline data of the 70 included patients are presented in Table 1. Of note is that nearly all patients were refractory to at least one anti-TNF and vedolizumab. Median follow-up was 16 weeks (IQR 13-26). Fifty-four percent (38/70) of patients required prolonged induction at 10mg BID. Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission, and endoscopic response and remission at week 8 and 16 are presented in Figures 1 and 2. Fifty percent (21/42) of the patients under steroids at baseline could have stopped steroids at 16 weeks. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5- 8) to 4 (IQR 2-7) after 8 weeks (n=49) (p<0.0001), and down to 2 (IQR 1-5) at week 16 (n=40) (p<0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5-6.2) (n=49) (p=0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism.
Conclusions
Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.