Rituximab in PR3-ANCA positive patients with moderately to severely active ulcerative colitis: a multicenter real-world pilot study

Background and aims Patients with ulcerative colitis (UC) and PR3-ANCA positivity often show a poor response to infliximab (IFX). Our objective was to compare the effectiveness and safety of rituximab (RTX) and IFX in moderately-to-severely active PR3-ANCA positive (PR3-ANCA+) UC patients. This study represents the first exploration of biomarker-guided therapy (PR3-ANCA+) in moderately-severely active UC, aiming to generate hypothesis-driven evidence for future randomized trials. Methods This retrospective, multicenter, real-world study focused on a rare biomarker-defined subgroup (PR3-ANCA + UC) and was conducted across three medical centers in Hubei, China. Moderately to severely active UC patients with PR3-ANCA+ were assigned to the RTX group (n = 12) and the IFX group (n = 26) based on biological therapy received. Endpoints at week 22 included clinical remission (primary), clinical response, endoscopic response, improvement, and remission. Safety endpoints centered on opportunistic infections and drug-related adverse events. Inverse probability of treatment weighting (IPTW) and multifactorial logistic regression analysis (MLRS) were used to reduce confounding effects. Results Pre-IPTW, compared with IFX, RTX significantly increased the rates of clinical remission, clinical response, endoscopic response, endoscopic improvement, and endoscopic remission by 60.25% (95%CI: 33.68%-86.82%, P P = 0.020), 65.38% (95%CI: 45.15%-85.61%, P P = 0.010), and 65.38% (95%CI: 45.15%-85.61%, P P = 0.002), 62.71% (95%CI: 46.35%-79.07%, P P = 0.024), and 62.71% (95%CI: 46.35%-79.07%, P P = 0.010; post-IPTW: OR = 47.692 (4.077-1,418.298), P = 0.007]. Additionally, for every 50% reduction in PR3-ANCA levels, the odds ratio (OR) for clinical remission was 7.583 (95%CI: 1.648-34.903). Furthermore, this conclusion remained robust after adjusting for confounding factors. For safety endpoints, no RTX patients had elevated tuberculosis interferon tests, while 2 IFX patients (7.69%) did. In addition, no HBV reactivation or infection occurred in either group. Mean IgG levels remained stable in RTX-treated patients (11.50 ± 3.59 vs. 10.84 ± 1.48, P = 0.569). Conclusion In moderately to severely active UC patients with PR3-ANCA+, RTX showed better effectiveness than infliximab (IFX), with a similar safety profile.