PATIENT-REPORTED HEALTH-RELATED QUALITY OF LIFE OUTCOMES WITH VEDOLIZUMAB VERSUS ADALIMUMAB TREATMENT OF ULCERATIVE COLITIS: RESULTS OF THE VARSITY TRIAL

Background: Patients with ulcerative colitis experience substantial impairment in quality of life (QOL). Patient QOL endpoints are important measures of treatment outcome. We evaluated the effects of intravenous vedolizumab vs adalimumab on QOL in VARSITY, the first head-to-head trial comparing the efficacy and safety of biologics in patients with moderately to severely active ulcerative colitis. Methods: VARSITY was a phase 3b, double-blind, double-dummy, randomized trial (NCT02497469; EudraCT 2015-000939-33). QOL was assessed by the inflammatory bowel disease questionnaire (IBDQ) at baseline, Week 30, and Week 52. Endpoints included clinically meaningful IBDQ improvement (an increase in total score of ≥16 points from baseline to Week 52), IBDQ remission (a total score of?>170 points at Week 52) and change from baseline in IBDQ-specific domain scores (bowel symptoms, systemic symptoms, emotional function, and social function) at Weeks 30 and 52. Serum C-reactive protein and fecal calprotectin (FCP) were also assessed as indicators of inflammation and ongoing disease activity. Results: Among randomized patients, 383 (vedolizumab) and 386 (adalimumab) patients received ≥1 dose of study drug (N=769). At Week 52, clinically meaningful IBDQ improvement was observed in 52.0% (vedolizumab) vs 42.2% (adalimumab) of patients (treatment difference 9.7%; 95% confidence interval, 2.7%-16.7%), while IBDQ remission was achieved by 50.1% (vedolizumab) vs 40.4% (adalimumab) of patients (treatment difference 9.6%; 95% confidence interval, 2.8%-16.5%). Mean (standard deviation) changes in IBDQ total score from baseline for observed cases favored vedolizumab over adalimumab (Week 30: 61.3 [39.8] vs 52.6 [42.8]; Week 52: 66.1 [41.8] vs 60.4 [42.2]; Figure 1). IBDQ subscores showed similar favorable trends for vedolizumab (Figure 2). Mean (standard deviation) changes from baseline in C-reactive protein for patients treated with vedolizumab vs adalimumab were –5.46 (17.19) mg/L vs –2.30 (24.92) mg/L at Week 30 and –5.34 (18.35) mg/L vs –3.91 (17.77) mg/L at Week 52. Mean (standard deviation) changes from baseline in FCP were similar, with –1,835.8 (6,958.0) µg/g vs –1,373.4 (4,679.4) µg/g at Week 30 and –2,187.3 (7,440.4) µg/g vs –1,846.6 (4,560.6) µg/g at Week 52 for vedolizumab vs adalimumab treatment, respectively. Among patients with FCP?>250 µg/g at baseline, the proportion of patients achieving FCP ≤250 µg/g was 33.9% vs 24.5% at Week 30 and 35.2% vs 28.9% at Week 52 for patients treated with vedolizumab vs adalimumab, respectively. Conclusion: Based on IBDQ total score and subscores, more patients with ulcerative colitis treated with vedolizumab than with adalimumab achieved clinically meaningful improvement and clinical remission. Reduced inflammation, as indicated by improvements in C-reactive protein and FCP, was consistent with improvements in QOL.