VOICE-Early Response to Vedolizumab and IL-23 Antagonists in Participants With Crohn's Disease: A Prospective Observational Study

Vedolizumab (VDZ), a monoclonal antibody that selectively targets intestinal T-cell trafficking, is an effective and safe treatment for moderately to severely active Crohn's disease (CD). Recent evidence from open-label, blinded endpoint studies such as VERSIFY and LOVE-CD provide further support for the efficacy of VDZ in achieving clinical, endoscopic, histologic and radiologic disease improvement in CD. Despite these data, VDZ is generally perceived to have a slower onset of action than other biologics, including tumor necrosis factor (TNF) antagonists and the interleukin (IL)-12/23 antagonist, ustekinumab (UST). The IL-23 antagonist risankizumab (RISA) has been more recently approved for treatment of CD and post-hoc analyses of SEQUENCE trial data showed RISA to be superior to UST for inducing clinical remission at Week 24, and thus, RISA may also be considered to have a quicker onset of action than VDZ. This perception largely emanates from the results of the VDZ pivotal for CD (GEMINI 2) where efficacy was assessed at Week 6 after only 2 doses in a largely refractory population. However, in clinical practice VDZ induction consists of 3 doses of VDZ 300 mg administered intravenously at weeks 0, 2 and 6 instead of the 2 doses used in the pivotal trials. In recent clinical trials, induction endpoints for therapeutics in CD are now typically measured at least after Week 12. Accordingly, it is uncertain whether the generally held perception of a relatively slow onset of action for VDZ is accurate. Moreover, it should also be noted that the perception of a slow onset of action has also been conflated to infer that VDZ is a relatively less effective induction therapy in CD than TNF antagonists or UST. Further data to evaluate these issues are needed.

Rapidity of symptom resolution, which is commonly used as a surrogate for speed of onset, is a priority for patients and clinicians. It is therefore important to better understand the kinetics of symptom improvement captured using patient-reported outcomes (PROs) in patients initiating VDZ for treatment of CD.

• To assess time of onset of biologic therapy in multiple QOL and functioning domains [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in pain interference through Week 52 through a reduction in PROMIS - Pain Interference - Short Form Scores. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in fatigue through Week 52 through a reduction in PROMIS - Fatigue - Short Form Scores. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in anxiety through Week 52 through a reduction in PROMIS - Emotional Distress - Anxiety - Short Form Scores. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in depression through Week 52 through a reduction in PROMIS Emotional Distress - Depression - Short Form. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in sleep disturbance through Week 52 through a reduction in PROMIS - Sleep Disturbance - Short Form. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in physical function through Week 52 through a reduction in PROMIS - Physical Function - Short Form. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess the efficacy of therapy in inducing a meaningful clinical improvement in ability to participate in social roles and activities through Week 52 through a reduction in PROMIS - Ability to Participate in Social Roles and Activities - Short Form. [Time frame: Baseline to Weeks 14, 30, and 52]
• To assess early change in patient-reported symptoms within the PRO-2 through Week 14. [Time frame: Baseline to Week 14]
• To assess early change in patient-reported symptoms within the PROMIS - Pain Interference - Short Form through Week 14 [Time frame: Baseline to Week 14]
• To assess early change in patient-reported symptoms within the PROMIS - Fatigue - Short Form through Week 14 [Time frame: Baseline to Week 14]
• To assess early change in patient-reported symptoms within the PROMIS - Anxiety - Short Form through Week 14 [Time frame: Baseline to Weeks 2, 6 and 14]