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

• Published in: Alimentary pharmacology & therapeutics 2018-04, Vol.47 (8), p.1117-1125
• Main Authors: Ben‐Horin, S., Ungar, B., Kopylov, U., Lahat, A., Yavzori, M., Fudim, E., Picard, O., Peled, Y., Eliakim, R., Del Tedesco, E., Paul, S., Roblin, X.
• Format: Article
• Language: English
• Subjects: Clinical trials; Corticosteroids; Exposure; Immunological memory; Infliximab; Lymphocytes; Lymphocytes T; Memory cells; Monoclonal antibodies; Patients; Pharmacokinetics; Remission; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.14567

Summary 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.