Anti-drug antibodies against anti-TNF in patients with inflammatory bowel disease: an evaluation of possible strategies

Abstract

Objective

Immunogenicity against anti-TNF antibodies usually leads to loss of response. We aimed to evaluate the efficacy of clinical strategies to improve clinical remission and pharmacokinetics upon detection of anti-drug antibodies (ADA).

Methods

Inflammatory bowel disease (IBD) patients with ADA against infliximab or adalimumab were identified through a single centre database search covering 2004-2022. Criteria for successful intervention upon ADA detection (baseline) were clinical remission after 1 year without further change in strategy.

Results

Two-hundred-and-fifty-five IBD patients (206 Crohn’s disease) were identified. At baseline, median ADA level was 77 AU/ml; 50.2% of patients were in clinical remission. Implemented strategies were: (1) 81/255 (32%) conservative management, (2) 102/255 (40%) anti-TNF optimisation, (3) 72/255 (28%) switch within or out of class. Switching was the most successful strategy for clinical remission (from 19% at baseline to 69% at 1 year, p < 0.001). Patients that continued the same dose anti-TNF or discontinued biological therapy were often in clinical remission, but deteriorated significantly (−22.7%, p = 0.004). Anti-TNF dose intensification with immunomodulator optimisation was the fastest (median 3.0 months, p = 0.009) and most effective (65% ADA suppression, p < 0.001) strategy to suppress ADA compared to solely anti-TNF or immunomodulator optimisation.

Conclusions

Switching therapy, within or out of class, is the most successful strategy to regain and maintain clinical remission upon immunogenicity. When switching to another anti-TNF, concomitant immunomodulatory therapy should be started or continued to prevent repeated immunogenic loss of response. Anti-TNF dose escalation with concomitant immunomodulator optimisation is the fastest and most effective strategy to suppress ADA.

Summary

Immunogenicity against anti-TNF antibodies is associated with loss of response in patients with inflammatory bowel diseases and remains a clinical challenge. We investigated potential therapeutic strategies in a retrospective patient cohort focusing on clinical efficacy and pharmacokinetics.

Keywords:

• Inflammatory bowel disease
• immunogenicity
• anti-TNF
• thiopurines

Disclosure statement

Suzanne I. Anjie declares no conflicts of interest. Jurij Hanzel has received speaker’s fees from Abbvie, Janssen, and Takeda; consulting fees from Alimentiv Inc. Krisztina B. Gecse has received grants from Pfizer Inc., Galapagos and Celltrion; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis, Takeda and Tillotts. Geert R. D’Haens has served as a speaker for Abbvie, Arena, Galapagos, Gilead, Pfizer, BMS and Takeda, consultancy fees for Abbvie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Progenity and Protagonist and ata montoring board for Galapagos, Astrazeneca and Seres Health. Johannan F. Brandse has served as a speaker for Galapagos and J&J. No potential conflict of interest was reported by the author(s).

Author contributions

S.I. Anjie collected and interpreted the data, designed the figures and wrote the first draft of the manuscript. All other authors contributed to design of the study and critically revised the manuscript for important intellectual content and approved the final version of the manuscript.

Data availability statement

The data underlying this article cannot be shared publicly due to privacy of individuals that participated in the study. Encoded data can be shared on reasonable request to the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.