Vedolizumab Ulcerative Colitis
*Acute severe colitis
*Mild-to-Moderate Ulcerative Colitis
*Probiotics in Ulcerative Colitis
*Methotrexate in Ulcerative Colitis
*Infliximab Ulcerative Colitis
*Infliximab with Azathiopurine (Ulcerative Colitis)
*Acute severe colitis: Accelerated induction Infliximab
*Adalimumab in Ulcerative Colitis (ULTRA studies)
*Golimumab in Ulcerative Colitis
*Vedolizumab vs Adalimumab Ulcerative Colitis
*Tofacitinib (OCTAVE Ulcerative Colitis)
*Ustekinumab (Ulcerative colitis)
*Acute severe colitis: Infliximab vs ciclosporin (CONTRUCT)
Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis
Brian G. Feagan, M.D., Paul Rutgeerts, M.D., Ph.D., Bruce E. Sands, M.D., Stephen Hanauer, M.D., Jean-Frédéric Colombel, M.D., William J. Sandborn, M.D., Gert Van Assche, M.D., Ph.D., Jeffrey Axler, M.D., Hyo-Jong Kim, M.D., Ph.D., Silvio Danese, M.D., Ph.D., Irving Fox, M.D., Catherine Milch, M.D., Serap Sankoh, Ph.D., Tim Wyant, Ph.D., Jing Xu, Ph.D., and Asit Parikh, M.D., Ph.D., for the GEMINI 1 Study Group
Background: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.
Methods: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
Results: Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.
Conclusions: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium
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). Twelve 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 multi-variable 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 naïve 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.
Narula N, Peerani F, Meserve J, et al. Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium [published correction appears in Am J Gastroenterol. 2018 Dec;113(12):1912]. Am J Gastroenterol. 2018;113(9):1345. doi:10.1038/s41395-018-0162-0