S Ben-Horin1,2, B Ungar1, U Kopylov1, A Lahat1, M Yavzori1, E Fudim1, O Picard1, Y Peled3, R Eliakim1, E Del Tedesco4, S Paul4, X Roblin4. 1. Department of Gastroenterology, Sackler School of Medicine, Sheba Medical Center Tel Hashomer, Tel-Aviv University, Tel Aviv, Israel. 2. First Affiliated Hospital of Sun-Yatsen University, Guangzhou, China. 3. Cardiology Department, Sheba Medical Center & Tel-Aviv University, Israel. 4. Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.
Abstract
BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM: To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS: Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study. RESULTS: Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4β7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). CONCLUSIONS: Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.
BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM: To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS:Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumabpatients in a retrospective 1:2 matched case-control study. RESULTS: Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4β7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). CONCLUSIONS:Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.
Authors: Neeraj Narula; Farhad Peerani; Joseph Meserve; Gursimran Kochhar; Khadija Chaudrey; Justin Hartke; Prianka Chilukuri; Jenna Koliani-Pace; Adam Winters; Leah Katta; Eugenia Shmidt; Robert Hirten; David Faleck; Malav P Parikh; Diana Whitehead; Brigid S Boland; Siddharth Singh; Sashidhar Varma Sagi; Monika Fischer; Shannon Chang; Morris Barocas; Michelle Luo; Karen Lasch; Matthew Bohm; Dana Lukin; Keith Sultan; Arun Swaminath; David Hudesman; Nitin Gupta; Bo Shen; Sunanda Kane; Edward V Loftus; Corey A Siegel; Bruce E Sands; Jean-Frederic Colombel; William J Sandborn; Parambir S Dulai Journal: Am J Gastroenterol Date: 2018-06-27 Impact factor: 10.864