Objectives: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment. Methods: Retrospective review (May 2014–December 2016) of VICTORY Consortium data. Adults with follow-up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC-related symptoms) and endoscopic remission (Mayo endoscopic sub-score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid-free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non-response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy. Results: We included 321 UC patients (71% prior TNFα antagonist exposure, median follow-up 10 months). The 12-month cumulative rates of clinical remission and endoscopic remission were 51% and 41%, respectively. Corresponding rates for corticosteroid-free remission and deep remission were 37% and 30%, respectively. Using NRI, 12-month rates were 20% (n = 64/321) for clinical remission, 17% (n = 35/203) for endoscopic remission, 15% (n = 30/195) for corticosteroid-free remission, and 14% (n = 28/203) for deep remission. A majority of the patients without adequate follow-up at 12 months who were deemed non-responders using NRI had already achieved clinical remission (n = 70) or a significant clinical response (n = 36) prior to 12 months. VDZ discontinuation prior to 12 months was observed in 91 patients, for lack of response (n = 56), need for surgery (n = 29), or adverse event (n = 6). On multivariable analyses, prior exposure to a TNFα antagonist was associated with a reduced probability of achieving clinical remission (HR 0.53, 95% CI 0.38–0.75) and endoscopic remission (HR 0.51, 95% CI 0.29–0.88). Serious adverse events and serious infections were reported in 6% and 4% of patients, respectively. Overall cumulative rates of colectomy over 12 months were 13%, with lower rates observed in patients naive to TNFα antagonist therapy (2%) than those who had been exposed to TNFα antagonists (19%). Conclusion: In this large real-world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.
Bibliographical noteFunding Information:
non-financial support from Janssen; grants from Broad Foundation, American College of Gastroenterology, Exact Sciences. PSD: research support from Takeda and Pfizer, and support from a training grant through the National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007202).
Guarantor of the article: Parambir S. Dulai. Specific author contributions: Acquisition of data (NN, FP, JM, GK, KC, JH, PC, JLKP, AW, LK, ES, RH, MP, DW, MB, DL, KS, AS, DH, NG, PSD). Statistical analysis (PSD). Drafting of manuscript (NN, FP, PSD). Critical revision of the manuscript for important intellectual content and final approval (all authors). Study supervision (PSD). Financial support: Takeda sponsored statistical analyses but had no access to data and all analyses were performed independently by the consortium. Potential competing interests: NN: has received grants, speaker fees, or advisory board fees from Abbvie, Allergan, Ferring, Janssen, Lupin, and Takeda. FP: Advisory Board honoraria from Janssen, Ferring and Takeda. JLKP: travel support from Takeda. ES: travel support from Takeda. KS: consulting Abbvie. Research Support from Takeda, Abbvie, Pfizer, Genentech, Celgene. DH: consulting for Abbvie, Takeda, Janssen. BSB: research support from Takeda, and support from CCFA career development award and UCSD KL2 (1KL2TR001444). SS: research support from Pfizer, and support from the American College of Gastroenterology and the Crohn’s and Colitis Foundation. BS: consulting for Janssen, Salix, Abbvie, Takeda, Theravence, Robarts Clinical Trials. CAS: consulting for Abbvie, Amgen, Celgene, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Takeda; speaker for CME activites for Abbvie, Janssen, Pfizer, Takeda; grant support from Abbvie, Janssen, Pfizer, and Takeda. EVL: consulting for Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Salix, Mesoblast, Eli Lilly, Celgene, and CVS Caremark; research support from Janssen, Takeda, AbbVie, UCB, Amgen, Pfizer, Genentech, Gilead, Receptos, Celgene, MedImmune, Seres Therapeutics, and Robarts Clinical Trials. SK: consultant to AbbVie, Janssen, Merck, Spherix Health, Pfizer, UCB. Research support from UCB. Board member ABIM. BES: consulting and research support from Amgen, Celgene, Janssen, Pfizer, Prometheus Laboratories, Takeda; consulting for AbbVie, Akros Pharma, Arena Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cowen Services Company, Forest Research Institute, Forward Pharma, Immune Pharmaceuticals, Lilly, Receptos, Salix Pharmaceuticals, Shire, Synergy Pharmaceuticals, Theravance Biopharma R&D, TiGenix, TopVert Pharma, UCB Vivelix Pharmaceuticals, Target Pharmasolutions, Allergan. JFC: consultancy/advisory board membership: AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Takeda, Theradiag; Speaker: AbbVie, Ferring, Takeda, Shire; Research support: AbbVie, Janssen and Janssen, Genentech, Takeda; Stock options: Intestinal Biotech Development, Genfit. WJS: personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr. August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Novo Nordisk, Mesoblast Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, Qu Biologics, Toray Industries Inc,, Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, personal fees from Ambrx Inc., Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, University of Western Ontario (owner of Robarts Clinical Trials); grants and personal fees from Prometheus Laboratories, AbbVie, Gilead Sciences, Boehringer-Ingelheim, Amgen, Takeda, Atlantic Pharmaceuticals, Bristol-Myers Squibb Genentech, GlaxoSmithKline, Pfizer, Nutrition Science Partners, Receptos, Amgen; grants, personal fees, and