Immunogenicity and Efficacy of Subcutaneous Infliximab Monotherapy vs Combination Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Abstract

Background & aims: Intravenous (IV) infliximab (IFX) combined with an immunomodulator (combination therapy) outperforms IV IFX monotherapy in terms of clinical, endoscopic, and immunogenicity outcomes in patients with inflammatory bowel disease (IBD). With the advent of subcutaneous (SC) IFX, which is associated with higher serum drug concentrations, it is essential to assess whether SC IFX monotherapy provides similar pharmacokinetic and clinical benefits as combination therapy.

Methods: We conducted a systematic review and meta-analysis (until August 2024), of studies on patients with IBD treated with SC IFX. The primary outcome was anti-drug antibodies (ADAs) formation within 12 months (M) after starting SC IFX or after switching from IV to SC IFX. Secondary outcomes included treatment persistence, clinical efficacy, and biochemical parameters.

Results: Twenty-four studies (N = 3172) were included. Among patients transitioning from IV IFX induction to SC IFX, immunogenicity was more prevalent with monotherapy than combination treatment (median, 68% vs 48%; odds ratio [OR], 3.29; 95% confidence interval [CI], 1.71-6.31; P < .001). Clinical response rates at 12M were comparable, with a trend favoring combination therapy (OR, 0.73; 95% CI, 0.50-1.06; P = .10). In patients switching from IV maintenance to SC IFX, relapse rates were low (median, 12% at 6M, 11% at week 50), with stable biochemical markers. Treatment persistence was high (93% at 6M, 92% at 12M). Among patients with quiescent disease at the time of switching, 1-year relapse rates were 9% to 11%, with baseline immunogenicity predicting treatment failure.

Conclusion: SC IFX monotherapy is associated with higher immunogenicity rates compared with combination therapy, particularly in new IFX starters. Although clinical response was comparable, a trend favoring combination therapy warrants further investigation.

Keywords: CT-P13; Immunogenicity; Inflammatory Bowel Disease; Infliximab; Subcutaneous.