Disease Control and Changes in Individual Treatment Outcomes from Week 14 to Week 52 with Vedolizumab or Adalimumab in Ulcerative Colitis: A VARSITY Trial Post Hoc Analysis

INTRODUCTION:

In VARSITY, vedolizumab (VDZ), an anti-a4b7 integrin antibody, achieved superior clinical, endoscopic and histologic outcomes vs adalimumab (ADA), an anti-tumor necrosis factor (TNF) agent, in patients with moderate-to-severe ulcerative colitis (UC) (1). In recent years, the therapeutic goal for UC has evolved from symptom relief to disease control across multiple outcomes.

METHODS:

This VARSITY post hoc analysis evaluated the trajectory of UC key endpoints and disease control with intravenous VDZ vs subcutaneous ADA between early (Week [W]14) and late (W52) time points. Evolution in disease control over time was assessed based on the proportion of patients who maintained, improved or lost treatment benefit from W14 to W52 for the efficacy endpoints clinical remission, endoscopic and histologic improvement (defined in Figure 1). Data were analyzed within treatment arms in the full analysis population and by prior anti-TNF use (anti-TNF näive or experienced). Observed data were reported without imputation.

RESULTS:

The study included 769 patients with UC (386 ADA, 383 VDZ). Most patients (56.0% ADA vs 60.8% VDZ) were male, were not using a corticosteroid at baseline (63.7% vs 63.9%) and were anti-TNF näive (79.0% vs 79.2%). Median UC duration was 4.5 (ADA) and 4.8 (VDZ) years. At W14 and W52, clinical remission, endoscopic and histologic improvement, and disease control were all achieved more frequently with VDZ vs ADA (Table 1). More patients maintained each efficacy outcome and disease control from W14 to W52 with VDZ vs ADA, in both anti-TNF subgroups (Figure 1). In both arms, more anti-TNF näive than anti-TNF experienced patients maintained efficacy (Figure 1). The numbers of patients who gained efficacy at W52 were more comparable between anti-TNF näive and experienced. At W52, the overall rate of disease control was higher with VDZ (47.3% anti-TNF näive vs 39.0% anti-TNF experienced) than ADA (32.7% vs 24.2%) (Table 1). Further analyses of early predictors of late disease control will be presented.

CONCLUSION:

VDZ treatment maintains greater early disease control than ADA in moderate-to-severe UC from W14 to W52, especially in anti-TNF näive patients. These data suggest that VDZ is superior to ADA during both induction treatment evaluated at W14 and maintenance treatment evaluated at W52. Most of the observed treatment differences in anti-TNF näive patients at W52 were established with early response to treatment between W0 and W14.