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%,< 0.001), 34.62% (95%CI: 16.33%-52.91%,= 0.020), 65.38% (95%CI: 45.15%-85.61%,< 0.001), 38.46% (95%CI: 10.65%-66.27%,= 0.010), and 65.38% (95%CI: 45.15%-85.61%,< 0.001), respectively. After IPTW, RTX remained associated with significantly higher rates of the above outcomes versus IFX, with increases of 53.68% (95%CI: 35.26%-72.10%, P = 0.012), 33.90% (95%CI: 16.52%-51.28%,= 0.002), 62.71% (95%CI: 46.35%-79.07%,< 0.001), 46.61% (95%CI: 26.83%-66.39%,= 0.024), and 62.71% (95%CI: 46.35%-79.07%,< 0.001), respectively. In MLRS, RTX was associated with higher odds of week-22 clinical remission compared with IFX, with consistent results before and after IPTW [pre-IPTW: OR = 31.022 (2.911-970.983),= 0.010; post-IPTW: OR = 47.692 (4.077-1,418.298),= 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 &#xb1; 3.59 vs. 10.84 &#xb1; 1.48,= 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.