Safety, efficacy and pharmacokinetics of vedolizumab in patients with simultaneous exposure to an anti-tumour necrosis factor

S. Ben-Horin*, B. Ungar, U. Kopylov, A. Lahat, M. Yavzori, E. Fudim, O. Picard, Y. Peled, R. Eliakim, E. Del Tedesco, S. Paul, X. Roblin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)1117-1125
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume47
Issue number8
DOIs
StatePublished - Apr 2018

Funding

FundersFunder number
7th
Chaim Sheba Medical Center
Leona M. and Harry B. Helmsley Charitable Trust

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