Reactive Immunomodulator Addition to Infliximab Monotherapy Restores Clinical Response in Inflammatory Bowel Disease:...

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Inflammatory bowel disease (IBD) patients on infliximab (IFX) often develop anti-drug antibodies (ADAs), leading to loss of response (LOR).
• Prophylactic use of immunomodulators (IMMs) with IFX induction reduces ADA formation and improves outcomes.
• This study investigates the efficacy of reactively adding an IMM to IFX monotherapy.

Purpose of the Study:

• To assess the impact of reactively adding an immunomodulator (IMM) to patients with inflammatory bowel disease (IBD) on infliximab (IFX) monotherapy.
• To evaluate the effect of reactive combination therapy (rCT) on anti-drug antibody (ADA) titers and IFX trough levels.

Main Methods:

• Retrospective cohort study and systematic review with meta-analysis.
• Included IBD patients with immunologic LOR on IFX monotherapy who received reactive combination therapy (rCT) with an IMM (azathioprine, 6-mercaptopurine, or methotrexate).
• Compared ADA and IFX trough levels pre- and post-IMM initiation; pooled effect size estimation using random-effects models.

Main Results:

• In a cohort of 6 patients, median ADA titer decreased by 85% (p=0.031) and median IFX trough increased 20.6-fold (p=0.038) after rCT.
• Meta-analysis of 7 studies (89 patients) showed an 87% ADA titer reduction and a 6.7-fold increase in IFX trough levels.
• The pooled clinical remission rescue rate was 76%.

Conclusions:

• Reactive combination therapy (rCT) is a valid strategy for patients with immunogenic loss of response to infliximab (IFX).
• rCT effectively reduces anti-drug antibody (ADA) titers and restores therapeutic IFX levels.
• This approach can recapture clinical remission in IBD patients experiencing IFX immunogenicity.