Marla C. Dubinsky, MD1, Marco DiBonaventura, PhD2, Haiyun Fan, MS3, Andrew G. Bushmakin, MS3, Joseph C. Cappelleri, PhD, MPH4, Eric Maller, MD3, Andrew J. Thorpe, PhD3, Leonardo Salese, MD3, Julian Panés, MD, PhD5
1Icahn School of Medicine at Mount Sinai, New York, NY; 2Pfizer Inc, New York, NY; 3Pfizer Inc, Collegeville, PA; 4Pfizer Inc, Groton, CT; 5Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain
Introduction: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Significant improvements have been reported in all Inflammatory Bowel Disease Questionnaire (IBDQ) domains for tofacitinib vs placebo (PBO) in patients (pts) with UC in OCTAVE Induction 1 & 2 and OCTAVE Sustain . The effect of tofacitinib on items within each IBDQ domain has not yet been analyzed.
Methods: We examined the effect of tofacitinib induction (10 mg twice daily [BID]) on individual IBDQ items in adults with moderate to severe UC. Data were pooled from the randomized, Phase 3 OCTAVE Induction 1 & 2 studies (NCT01465763 & NCT01458951) . Pts self-administered the IBDQ at baseline (BL), Week (Wk) 4, and Wk 8. IBDQ domains are: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items); higher scores indicate better health-related quality of life (HRQoL) [1,3]. Change from BL (CFB) in IBDQ items was analyzed for tofacitinib vs PBO using a linear mixed-effects model, with fixed effects (treatment, study, prior tumor necrosis factor inhibitor treatment, BL corticosteroid use, geographical region, week, treatment-by-week interaction, and BL score) and a random effect (pts). No multiplicity adjustment was performed.
Results: Significant improvements (p< 0.05) were observed in all IBDQ items with tofacitinib 10 mg BID vs PBO at Wks 4 and 8. The largest treatment differences (CFB; domain) were: ‘bowel movements been loose’ at Wks 4 and 8 and also ‘problem with rectal bleeding’ at Wk 8 (all 1.1 points) for the bowel symptoms domain; ‘getting a good night's sleep’ at Wk 4 (0.8) and 8 (0.9) for the systemic symptoms domain; ‘fear of not finding a washroom’ at Wk 4 (0.6) and 8 (0.8) and also ‘felt embarrassed’ and ‘felt angry’ at Wk 4 (both 0.6) for the emotional function domain; and ‘avoid attending events’ at Wk 4 (0.8) and 8 (1.0) and also ‘difficulty doing leisure/sports’ at Wk 8 (1.0) for the social function domain (Table).
Discussion: Tofacitinib improved all bowel-related and systemic symptoms, and all emotional and social functioning IBDQ items vs PBO, highlighting the broad impact of tofacitinib on HRQoL. This analysis provides a useful perspective on the most improved IBDQ domains with tofacitinib induction therapy, which may facilitate patient-physician dialogue.
Citation: Marla C. Dubinsky, MD; Marco DiBonaventura, PhD; Haiyun Fan, MS; Andrew G. Bushmakin, MS; Joseph C. Cappelleri, PhD, MPH; Eric Maller, MD; Andrew J. Thorpe, PhD; Leonardo Salese, MD; Julian Panés, MD, PhD. P0509 - ITEM-LEVEL IMPROVEMENTS IN INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE SCORES IN PATIENTS WITH ULCERATIVE COLITIS TREATED WITH TOFACITINIB INDUCTION THERAPY. Program No. P0509. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.