Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

Background & Aims: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2). Methods: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein. Results: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups. Conclusions: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951. © 2019 AGA Institute