Rituximab in PR3-ANCA Positive Patients with Moderately to Severely Active Ulcerative Colitis: A Multicenter Real-World Pilot Study

Qi Yu^*Yiyu ChengHuan WangYidong ChenFang LiuXiaopeng ZhangXiaoyu FuJiamin LiJunrong LiYing LiLiangru Zhu^*

• Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background and Aims: Patients with ulcerative colitis (UC) and PR3-ANCA positivity often s how 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. 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 analysi s (MLRS) were used to reduce confounding effects. Results: Pre-IPTW, compared with IFX, RTX significantly increased the rates of clinical remiss ion, clinical response, endoscopic response, endoscopic improvement, and endoscopic remission by 60.25% (95%CI: 33.68%-86.82%, P<0.001), 34.62% (95%CI: 16.33%-52.91%, P=0.020), 65. 38% (95%CI: 45.15%-85.61%, P<0.001), 38.46% (95%CI: 10.65%-66.27%, P=0.010), and 65.3 8% (95%CI: 45.15%-85.61%, P<0.001), respectively. After IPTW, RTX remained associated wit h 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%, P=0.002), 62.71% (95%CI: 46. 35%-79.07%, P<0.001), 46.61% (95%CI: 26.83%-66.39%, P=0.024), and 62.71% (95%CI: 46.3 5%-79.07%, P<0.001), respectively. In MLRS, RTX was associated with higher odds of week-2 2 clinical remission compared with IFX, with consistent results before and after IPTW [pre-IPT W: OR=31.022(2.911-970.983), P=0.010; post-IPTW: OR=47.692(4.077-1418.298), P=0.007]. Ad ditionally, for every 50% reduction in PR3-ANCA levels, the odds ratio (OR) for clinical r emission was 7.583 (95%CI: 1.648-34.903). Furthermore, this conclusion remained robust a fter adjusting for confounding factors. For safety endpoints, no RTX patients had elevated tu berculosis 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 (P=0.569). Conclusions: In moderately to severely active UC patients with PR3-ANCA+, RTX showe d better effectiveness than infliximab (IFX), with a similar safety profile.