P662 Efficacy and safety of tofacitinib in patients with moderate-to-severe ulcerative colitis: A real-world retrospective study

Abstract

Background Tofacitinib is an orally active, small-molecule Janus kinase inhibitor, recently approved for the treatment of moderate to severe ulcerative colitis (UC) refractory to corticosteroid. However, currently, there is inadequate evidence for efficacy of Tofacitinib in UC patients. Therefore, our objective was to evaluate the efficacy and safety of Tofacitinib for inducing and maintaining remission in UC patients. Methods In a single-centre retrospective setting, 71 consecutive patients with UC who had failed to respond to corticosteroid or biologics were included. All patients had received 10mg Tofacitinib orally twice daily for at least 8 weeks as remission induction therapy and then, the responders received 5mg twice daily as maintenance therapy for up to 26 weeks. The clinical response and adverse events were evaluated at weeks 8 (induction) and 26 (maintenance). UC activity was assessed by the partial Mayo score. Clinical remission was defined as p-Mayo score ≤1 and the bleeding subscore = 0. Clinical response was defined as p-Mayo score ≤4 and a decrease of ≥3 points relative to baseline. Furthermore, the cumulative remission rates up to 26 weeks were determined by the Kaplan–Meier survival analysis. Results At week 8, 24 of 71 patients (33.8%) achieved clinical remission and 20 (28.2%) achieved response level. The mean p-Mayo score fell from 5.8 ± 1.1 at entry to 3.5 ± 2.3 at week 2 (p < 0.01) and 2.3 ± 1.9 at week 8 (P<0.01). The average total cholesterol increased from 180.8 ± 36.0 mg/dl at entry to 206.8±39.3 mg/dl (p < 0.01). In anti-tumour necrosis factor (TNF)-α or vedolizumab (VDZ) naïve subgroup (n = 14), 8 patients (57.1%) achieved response level, while in biologic failure subgroup (n = 57), 36 patients (63.2%) achieved response level. In single biologic failure subgroup (n = 27), 19 patients (70.4%), in double biologics failure subgroup, 14 of 24 patients (58.3%), and in 3 biologics failure subgroup, 3 of 6 patients (50.0%) achieved response level, showing a decrease in the efficacy of Tofacitinib in patients who had failed more than one biologic. Furthermore, of the 25 patients followed for 26 weeks, 23 (92.0%) sustained remission at week 16 and 19 (76.0%) at week 26. Herpes virus infection occurred in 4 patients. The increase in total cholesterol was observed in 68.8% of the patients. Conclusion Our retrospective efficacy assessment indicated that Tofacitinib was effective and safe for inducing and maintaining remission in corticosteroid refractory UC patients, regardless of biologic naïve or failure background. The efficacy of 10mg twice daily was rapid and observed within 2 weeks of starting the treatment.

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis

“…Of the 202 citations identified with the search strategy, 17 studies including 1162 patients with UC were eligible to be included in this review. [5][6][7][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Supplementary Table 1). Six studies were reported as full-text articles, and 11 were conference proceedings.…”

“…Three studies compared response rates according to prior biologic exposure. 17,19,24 Response at week 8 was achieved in 58.1% of patients who were bio-experienced (95% CI, 49.3-66.7) versus 83% of patients who were biologic-naïve (95% CI, 56.5-99.2; Supplementary Fig. 3).…”

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis

“…After excluding 32 studies for reasons documented in Figure 1, 24 articles representing 26 independent studies were included in our analysis. 7,[10][11][12][13][14][15][16][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] An RCT study design was used in 4 studies, 7,34 and the rest were observational designs. Twenty studies reported efficacy outcomes 7,[10][11][12][13][14][15][16]31,[33][34][35][36][37][38][39][40]42,44,45 and 25 studies reported safety outcomes.…”

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study

“… 23 Real-life Japanese studies have reported week 8 clinical remission and response rates of 27.7–50.5% and 46.6–66.3%, respectively. 24 – 27 They have also reported that 41–43.5% and 45–47.1% of patients showed remission and response at weeks 48–52, respectively. 26 , 27 These results were also slightly numerically different from those of our study, probably because of the difference in the patients’ characteristics and the definitions of clinical outcomes.…”

“… 23 However, real-world studies on the effectiveness and safety of tofacitinib in Asian patients have still been limited to a single-center-based design and no reports from Korea are yet available. 24 – 28 …”