Exposure-efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn's disease and ulcerative colitis

Background and aims: This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure-efficacy of vedolizumab intravenous (IV) and subcutaneous (SC). Methods: A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C-av,C-ss, C-trough,C-ss) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score <= 2 points and no individual subscore > 1 point (UC), and CD activity index score <= 150 points (CD). Results: Data were from 1968 patients (GEMINI 1 [n = 334], VISIBLE 1 [n = 216], GEMINI 2 [n = 1009], VISIBLE 2 [n = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted C-av,C-ss for IV-Q8W and SC-Q2W was similar in UC and CD. C-av,C-ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. C-trough,C-ss values from IV and SC aligned well with pooled observed C-trough by treatment group in UC and CD. C-av,C-ss was equivalent for SC and IV. For UC and CD, efficacy rates were greater in patients in the highest quartiles of vedolizumab exposure for both formulations. Conclusion: Exposure-efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.