Abstract
Background
Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking monoclonal anti-a4β7-integrin antibody, has showed efficacy in multiple phase 3 clinical trials in patients (pts) with inflammatory bowel disease (IBD). Decreased likelihood of response to adalimumab was previously observed with concomitant 5-ASA.1 This post-hoc analysis assessed the impact of concomitant 5-ASA on efficacy and safety in VDZ-treated pts with IBD.
Methods
Pts with IBD treated with VDZ intravenous (IV) or subcutaneous (SC) in phase 3 trials who continued 5-ASA (at any dose) at the time of starting VDZ were compared with those who received no concomitant 5-ASA. Pts were also stratified by ulcerative colitis (UC) or Crohn’s disease (CD). Efficacy outcomes were the proportion of pts achieving clinical response, clinical remission and corticosteroid (CS)-free clinical remission at Wk 6 (end of induction phase) and Wk 52 (end of maintenance phase). Safety outcomes were the proportion of pts experiencing any infection and enteric infections. Studies included: GEMINI 1 and 2, and VISIBLE 1 and 2 in efficacy analyses; GEMINI 1, 2, 3 and long-term safety for VDZ IV, and VISIBLE 1, 2, and open-label extension (data cut-off 17 May 2019) for VDZ SC in safety analyses.
Results
At Wk 6, clinical response was achieved by 191 (70.0%) and 69 (61.6%) VDZ-treated pts with UC with and without 5-ASA, respectively, and by 139 (64.4%) and 161 (57.7%) pts with CD, respectively (Table 1). At week 52, clinical remission was achieved by 134 (46.0%) and 45 (38.8%) VDZ-treated pts with UC with or without 5-ASA, and by 116 (50.2%) and 132 (37.5%) pts with CD, respectively. CS-free clinical remission at Wk 52 was achieved by 55 (34.8%) and 19 (37.3%) VDZ-treated pts with UC with and without 5-ASA, respectively, and by 46 (41.4%) and 46 (31.5%) pts with CD, respectively. Multivariate analysis in general showed no differences in VDZ efficacy with or without 5-ASA. No new safety issues or signals were identified. A tendency towards lower incidence of all infections and enteric infections was observed in pts receiving VDZ (IV or SC) with versus without 5-ASA (Table 2).
Conclusion
In this post-hoc analysis of VDZ pivotal trial data, concomitant 5-ASA does not appear to significantly impact the efficacy of VDZ in pts with IBD. No new safety signals were identified. The safety profile of VDZ IV and SC, with and without 5-ASA was consistent with the known safety profile of VDZ. Although there was limited data in some subgroups, there was no evidence to suggest that concomitant 5-ASA usage was associated with higher infection rates. These data will be useful to inform risk-benefit assessments of continued 5-ASA in VDZ-treated pts.
Reference
Corrigendum to: Renal Impairment, C. difficile Recurrence, and the Differential Effect of Bezlotoxumab: A Post Hoc Analysis of Pooled Data From 2 Randomized Clinical Trials
