Treatment persistence of ustekinumab and vedolizumab in IBD patients is independent of prior immunogenicity to anti-TNFs: a retrospective study

Abstract

Background and aims

Immunological treatment failure of anti-TNF therapy negatively influences treatment persistence of a second anti-TNF in IBD patients. So far it is unknown if this effect is also observed for other monoclonal antibodies. We assessed the influence of immunogenicity to anti-TNFs on treatment persistence of subsequent ustekinumab and vedolizumab therapy.

Methods

IBD patients with and without immunogenicity to anti-TNFs (undetectable trough levels and antibody titers ≥20 ng/mL) and subsequent ustekinumab (UST) and/or vedolizumab (VDZ) therapy were included in this retrospective, single-center study. The Kaplan-Meier method with the log-rank test and Cox proportional hazards were used as statistical methods.

Results

One hundred patients (Crohn’s disease: 62, Ulcerative colitis: 31, IBD unclassified: 7) with 127 treatment lines (62 with UST, 65 with VDZ) were included in the analysis. Immunogenicity to previous anti-TNFs did not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy (UST: Log rank: p = .95, Immunogenicity: HR for treatment discontinuation: 0.97 [95% CI 0.31–3.04]; VDZ: p = .65, HR: 0.85 [0.41–1.75]; total cohort [UST and VDZ]: p = .62, HR: 0.86 [0.47–1.57]). Azathioprine co-treatment did not lengthen treatment persistence (UST: Log rank: p = .77, azathioprine: HR: 1.20 [0.34–4.27]; VDZ: p = .92, HR: 0.58 [0.17–1.99]; total cohort: p = .79, HR: 1.10 [0.55–2.20]). In this anti-TNF experienced cohort, patients with ustekinumab remained longer on treatment than patients receiving vedolizumab (Log rank: p = .005, UST: HR: 0.43 [0.23–0.79]).

Conclusions

Immunogenicity to anti-TNFs does not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy.

Keywords:

• Inflammatory bowel disease
• Crohn’s disease
• ulcerative colitis
• immunogenicity
• anti-TNF
• vedolizumab
• ustekinumab

Ethical approval

The study was approved by the research ethics committees at the Medical University of Graz (EK 31-089 ex 18/19) and was registered at clinicaltrials.gov (NCT04575701).

Author contributions

AB planned the study, acquired data, analyzed data, interpreted data and drafted the manuscript. LB, SF, HW, FBD and PK acquired data and critically reviewed the manuscript. WP and CH planned the study, acquired data, interpreted data and critically reviewed the manuscript.

Disclosure statement

AB has received consulting fees, speaker fees, and travel grants from AbbVie, Aengus, Bristol-Myers Squibb, Dr. Falk Pharma, Genericon, Gilead, Janssen, MSD, Olympus, Pfizer, Takeda, Vifor. WP has received consulting fees and speaker fees from AbbVie, Dr. Falk Pharma, MSD, Takeda. LB declares no competing interests. SF has received speaker fees from Takeda. HW has received consulting fees, speaker fees, and/or travel grants from AbbVie, Dr. Falk Pharma, Takeda. FBD has received speaker fees and travel grants from AbbVie, Bristol-Myers Squibb, Falk, Gilead, Janssen, MSD, Pfizer, Takeda. P.K. has received research funding from Bristol Meyer Squibb and Ipsen and has received consulting and speaker fees from AbbVie, Gebro, Ipsen, Janssen, Novartis, MSD, Pfizer, Takeda. CH has received consulting fees, speaker fees, and/or travel grants from AbbVie, Dr. Falk Pharma, Ferring, Gilead, Janssen, MSD, Pfizer, Takeda.

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.