P0584 Rituximab versus infliximab for the treatment of PR3-ANCA Positive Moderately to Severely Active Ulcerative Colotis: A retrospective Multicentre Real-World Study

Abstract Background Patients with ulcerative colitis (UC) who are positive for anti-neutrophil cytoplasmic antibodies(ANCA) tend to have a poor response to infliximab(IFX)1-3. We aimed to evaluate the comparative efficacy and safety of rituximab (RTX) versus IFX in moderately to severely active UC patients who are Proteinase 3-ANCA(PR3-ANCA) positive. Methods This retrospective multicentre real-world study encompassed three medical centres in Hubei, China. Patients with moderate to severely active UC who are positive for PR3-ANCA were categorized into the RTX group(100mg or 200mg by intravenous injection every 2 weeks for a total dose between 400mg and 900mg, n=12) and IFX group(5 mg/kg of intravenous at weeks 0, 2, and 6, followed by maintenance doses every 8 weeks, n=26) based on the biological therapy. The Mayo Clinic Score (MCS) was utilised to evaluate the efficacy endpoints at week 22, encompassing clinical remission(primary endpoint), clinical response, endoscopic response, endoscopic improvement, and endoscopic remission. Safety endpoints focused on opportunistic infections and drug-related adverse reactions. Inverse probability of treatment weighting(IPTW) and multifactorial logistic regression analysis(MLRS) were employed to mitigate the effects of potential confounding factors. Results The rates of clinical remission(83.33% vs. 23.08% and 93.20% vs. 25.40%), clinical response(100.00% vs. 65.38% and 100.00% vs. 64.60%), endoscopic response(100.00% vs. 34.62% and 100.00% vs. 36.06), endoscopic improvement(50.00% vs. 11.54% and 75.07% vs. 11.29%), and endoscopic remission(100.00% vs. 34.62% and 100.00% vs. 36.06%) were significantly higher in patients treated with RTX compared with those treated with IFX, both prior to and following IPTW(all P<0.05). In MLRS, RTX was associated with higher odds of achieving clinical remission at week 22 versus IFX before and after IPTW[OR(95%CI): 143.854(1.060-19521.653) and 190.499(4.147-1.000*105), all P<0.05]. In terms of safety endpoints, elevated interferon-gamma release assays(IGRAs) were noted in none of the RTX patients, and 2 IFX patients (7.69%). No patients exhibited elevated EBV-DNA, HBV-DNA, CMV-DNA, or experienced severe infections. Conclusion RTX demonstrated superior efficacy versus IFX in moderately to severely active UC patients with positive PR3-ANCA, with a comparable safety profile. References 1. Yoshida A, Matsuoka K, Ueno F, Morizane T, Endo Y, Hibi T. Serum PR3-ANCA Is a Predictor of Primary Nonresponse to Anti-TNF-α Agents in Patients with Ulcerative Colitis. Inflammatory intestinal diseases. May 2021;6(2):117-122. doi:10.1159/000515361 2. Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflammatory bowel diseases. Feb 2007;13(2):123-8. doi:10.1002/ibd.20054 3. Jürgens M, Laubender RP, Hartl F, et al. Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. The American journal of gastroenterology. Aug 2010;105(8):1811-9. doi:10.1038/ajg.2010.95