DOP075 Tofacitinib in active ulcerative colitis: Analysis of efficacy based on patient-reported outcomes

Abstract

Background: Tofacitinib, a novel oral Janus kinase inhibitor being investigated as a targeted immunomodulator, demonstrated dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC) in a Phase 2 randomised controlled trial (Clinicaltrials.gov NCT00787202; Pfizer Inc A3921063). Reported here is the effect of tofacitinib on patient-reported outcomes (PROs), including aspects of health-related quality of life (HRQoL) and patient preference for study medication, in the same patient population. Methods: Patients ( 18 years of age, n = 194) with active UC (total of full Mayo score 6 12 points and moderately-toseverely active disease on sigmoidoscopy) were randomised in a 2:2:2:3:3 ratio to receive twice daily (BID) oral tofacitinib 0.5mg (n = 31), 3mg (n = 33), 10mg (n = 33) or 15mg (n = 49) or placebo (n = 48) for 8 weeks. PROs included the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact (IBD PRTI) questionnaire. Relationships were assessed with Pearson correlation coefficients, logistic regression for binary outcomes and linear regression for continuous outcomes. Results: At Week 8 mean IBDQ total scores improved relative to baseline across all 5 treatment groups (baseline range 123.2 134.5; Week 8 range 149.6 175.4); improvement was significantly greater for tofacitinib 15mg BID vs. placebo (mean ± std dev: 50.7±35.6 vs. 27.8±29.8, P= 0.001). At Week 8 patients receiving tofacitinib 15mg BID had an odds ratio of 4.18 (95%CI: 1.75 10.02; P< 0.001) to achieve an IBDQ response ( 16-point improvement) and an odds ratio of 5.23 (95%CI, 2.14 12.75; P< 0.001) to achieve IBDQ remission (total IBDQ score of 170) relative to placebo-treated patients. At Week 8, IBDQ total score significantly correlated with the full Mayo score (r = 0.62, P< 0.0001) and Mayo endoscopy subscore (r = 0.46, P< 0.0001). For the three PRTI questions (satisfaction, preference, willingness), at Week 8 the majority of patients receiving tofacitinib 15mg BID reported being “satisfied” or “extremely satisfied” with the drug received, definite preference for the study drug, and definite willingness to use the study drug again. Patients achieving endoscopic remission (Mayo endoscopy score of 0) had significantly more favourable (P< 0.05) IBDQ scores and PRTI scores than those not achieving endoscopic remission. Conclusions: Short-term treatment with oral tofacitinib was associated in patients with moderately-to-severely active UC with dose-dependent improvement of HRQoL and in patient preference for the study medication. The results complement reported efficacy and safety data from the same trial.