P0638 Impact of immunogenicity on 2-year clinical outcomes in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab: A post hoc analysis of the Phase 3 LIBERTY-CD study
Authors: Sands B E , Colombel J F , Rubin D T , Schreiber S , Siegel C A , Yarur A , Danese S , Kang A , Kim D H , Lee Y N , Hanauer S B 
Published: January 2025

Abstract

Background
Development of anti-drug antibodies (ADA) is a marker for negative long-term outcomes in patients (pts) with Crohn’s disease (CD) treated with biologics.1,2Post hoc analysis of the Phase 3 LIBERTY-CD study suggested that ADA occurrence did not have an overall impact on drug persistence and clinical efficacy of subcutaneous (SC) infliximab (IFX), despite leading to lower serum IFX levels.3 The current study evaluated the long-term impact of immunogenicity on clinical outcomes up to Week (W) 102 in pts who received IFX SC maintenance treatment.

Methods
This analysis included W10 responders to induction therapy with intravenous IFX, who were randomised to the IFX SC arm in the LIBERTY-CD study. ADAs were measured using a highly sensitive, drug-tolerant electrochemiluminescent affinity capture elution assay. Pts were divided into two groups according to ADA occurrence (ADA-positive, ≥1 ADA-positive sample any time after treatment initiation; ADA-negative, no ADA-positive samples throughout the treatment). Groups were balanced using propensity score matching (PSM) with a 2:1 ratio. Drug persistence, efficacy outcomes and serum IFX levels were compared between ADA-positive and ADA-negative pts at or up to W102.

Results
Among the 231 pts randomised to the IFX SC arm, baseline differences in age, weight, body mass index (BMI) and prior exposure to biologics and/or Janus kinase inhibitors (JAKi) were seen between ADA-positive and ADA-negative groups. Following PSM by BMI and prior exposure to biologics and/or JAKi, baseline characteristics were balanced between the ADA-positive (n=105) and ADA-negative (n=58) groups (Table). Drug persistence was comparable between ADA-positive and ADA-negative pts up to W102 (log-rank p=0.32; Figure). There were no significant differences in the proportion of pts achieving efficacy outcomes at W102 between ADA-positive and ADA-negative groups (clinical remission: 57.1% vs 46.6%, respectively, p=0.2510; endoscopic response: 40.0% vs 50.0%, respectively, p=0.2497). Mean serum IFX levels were higher in ADA-negative pts (14.9–20.6 µg/mL) than ADA-positive pts (11.5–13.9 µg/mL) throughout the maintenance phase. Despite no difference in drug persistence and clinical remission rates, pts who had an ADA titre ≥1,000 during maintenance therapy had a lower rate of endoscopic response at W102 compared to ADA-negative pts (8.3% vs 50.0%).

Conclusion
ADA occurrence did not have a significant impact on drug persistence of IFX SC up to W102. Drug levels were lower in ADA-positive than ADA-negative pts, but stable throughout the study in both groups. ADA titres may be relevant to long-term efficacy. Further study of ADA titres is warranted to identify thresholds that may impact long-term outcomes.

References
1. Velikova T, et al. Antibodies. 2024;13(1):16.
2. Baert F, et al. N Engl J Med. 2003;348:601-608.
3. Colombel JF, et al. J Crohns Colitis. 2024;18(suppl 1):i1614-1615.