title: Direct and Indirect Effects of Tofacitinib on Treatment Satisfaction in Patients with Ulcerative Colitis.
abstract: OBJECTIVE
  This mediation modelling analysis evaluated direct and indirect effects of tofacitinib, an oral, small molecule Janus kinase inhibitor under investigation for ulcerative colitis, on patient treatment satisfaction.
  
  
  METHODS
  Data from an 8-week randomized Phase 2 trial [NCT00787202] in adults with moderate-to-severe, active ulcerative colitis receiving twice-daily tofacitinib 0.5-15mg [n=146] or placebo [n=48] were analysed in patient-reported [n=149] and clinician-reported [n=170] outcomes-based mediation models. Binary predictor variable: Treatment [pooled active treatment vs placebo]. Eventual dependent variable: Week 8 patient treatment satisfaction [measured on a five-point Likert scale]. Mediators of treatment effect on satisfaction: Week 8 Inflammatory Bowel Disease Questionnaire domains [Bowel Symptoms, Emotional Health, Social Function and Systemic Symptoms] and Mayo scale domains [Stool Frequency, Rectal Bleeding, Physician's Global Assessment and Endoscopic Disease Activity] for patient-reported and clinician-reported models, respectively.
  
  
  RESULTS
  Overall tofacitinib indirect effect on satisfaction via Inflammatory Bowel Disease Questionnaire domains was 40.5% [p<0.05] and via Mayo scale domains was 84.0% [p<0.01] for patient-reported and clinician-reported models, respectively. Bowel function had the most important indirect effect: of the total tofacitinib effect on satisfaction, 32.4% [p=0.05] was indirectly mediated via Bowel Symptoms; and 30.0% [p=0.04] via Stool Frequency. In total, 59.5% [p<0.01] and only 16.0% [p=0.56] of tofacitinib's effect on satisfaction was unrelated to Inflammatory Bowel Disease Questionnaire and Mayo scale domains in the patient-reported and clinician-reported models, respectively.
  
  
  CONCLUSIONS
  Bowel function is an important factor for patient treatment satisfaction with tofacitinib. Treatment effect on patient satisfaction was almost completely mediated via improvement in Mayo scale domains.
authors.affiliation: Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain jpanes@clinic.ub.es.
authors.forename: Julian
authors.initials: J
authors.lastname: Panés
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Chinyu
authors.initials: C
authors.lastname: Su
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bushmakin
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Healey
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017060:Patient Satisfaction / Q000706:statistics & numerical data; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D012074:Remission Induction; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: Inflammatory bowel disease; mediation modelling; tofacitinib