Webber Chan1,2, Nicole Lynch1, Peter Bampton3, Jeff Chang4, Alvin Chung5, Timothy Florin6, David J Hetzel7, Simon Jakobovits8, Gregory Moore9, Paul Pavli10, Graham Radford-Smith11, Lena Thin12, Brandon Baraty1, Craig Haifer1, Yunki Yau1, Rupert W L Leong1. 1. Gastroenterology and Liver Services, Concord Repatriation General Hospital. 2. Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore. 3. Department of Gastroenterology and Hepatology, Flinders Medical Centre, Bedford Park, South Australia. 4. Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney. 5. Department of Gastroenterology, Box Hill Hospital, Melbourne, Victoria. 6. Mater Research, University of Queensland, Queensland. 7. Department of Gastroenterology, Royal Adelaide Hospital, Adelaide. 8. Department of Gastroenterology, Alfred Health. 9. Department of Gastroenterology, Monash Health, Melbourne. 10. Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra, Australian Capital Territory. 11. Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane. 12. Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Fremantle, Western Australia, Australia.
Abstract
BACKGROUND: Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. AIM: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. MATERIALS AND METHODS: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. RESULTS: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. CONCLUSION: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.
BACKGROUND:Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. AIM: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. MATERIALS AND METHODS: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. RESULTS: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. CONCLUSION: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.
Authors: Mark Samaan; Samantha Campbell; Georgina Cunningham; Aravind Gokul Tamilarasan; Peter M Irving; Sara McCartney Journal: F1000Res Date: 2019-07-29