Vedolizumab (VDZ) is used to treat moderately-to-severely active Crohn's disease (CD) and ulcerative colitis (UC). Loss of response (LOR) to anti-TNF therapy at 12 months occurs in up to 46% of patients and can often be managed with dose intensification. Rates and risk factors for LOR to VDZ and recapture of patients following dose intensification have not been reported but are of clinical importance.Methods:
Institutional review board approval for data collection and sharing were obtained to create the Vedolizumab for Health Outcomes in Inflammatory Bowel Disease (VICTORY) consortium. Patients were included in the current analysis if they had moderately-to-severely active disease (based on endoscopy or clinical indices) prior to starting VDZ and at least one follow-up to assess for response to therapy. Clinical remission and response were based on the physician global assessment and defined as complete resolution of all symptoms or a >50% reduction in symptom frequency or severity, respectively. LOR was defined as recurrence or worsening of symptoms after achieving remission or response that required VDZ dose intensification, addition of concomitant therapy, or discontinuation of VDZ. Success of recapture was defined as achieving clinical remission and/or >50% reduction in symptom activity. Univariable and multivariable Cox proportional hazard analyses were used to assess the association of various factors with time to LOR, and were expressed as hazard ratios (HR) with 95% Confidence Intervals (CI), with a HR >1 indicating increased probability for having a LOR.Results:
A total of 507 IBD patients (CD, n = 293; UC, n = 214) with moderately-to-severely active disease and a median follow-up of 270 days (interquartile range [IQR], 160–408) were included in the analysis. Prior exposure to anti-TNF therapy was seen in 415 patients (CD, n = 269; UC, n = 146), with 260 having been exposed to 2 or more anti-TNF agents (CD, n = 205; UC, n = 55). A total of 230 patients (CD, n = 115; UC, n = 115) achieved a clinical response, among whom, 144 (CD, n = 61; UC, n = 83) achieved clinical remission. The cumulative rates of LOR at 6 and 12 months were 28% (CD, 25%; UC, 30%) and 47% (CD, 51%; UC, 45%), respectively. The median time to LOR was 143 (IQR, 67–270) days. On multivariable analysis, patients with a baseline albumin of less than 3 g/dL were more likely to have a LOR (HR, 2.18; 95% CI, 1.08–4.42), and the risk for LOR was incremental according to the number of anti-TNF agents previously used (HR, 1.26; 95% CI, 1.03–1.54). Shortening of VDZ interval (every 4 or 6 weeks) to re-capture response was attempted in 53 patients, with success in 36% (n = 19/53).Conclusions:
Cumulative rates for LOR with VDZ are similar to those seen with anti-TNF therapy, and response can similarly be re-captured with dose intensification in over one third of patients. Baseline albumin and the number of anti-TNF agents previously used were identified to be independent predictors of LOR. Further studies are needed to assess the pharmacokinetics and pharmacodynamics of VDZ, and the optimal dosing strategy in individuals with high drug clearance.