Insights into the treatment of infliximab and vedolizumab in positive PR3-ANCA patients with moderately to severely active ulcerative colitis: multicenter real-world evidence

Abstract Background and aims Perinuclear anti-neutrophil cytoplasmic antibody(p-ANCA) positivity may indicate poor response to infliximab (IFX) in ulcerative colitis (UC). Nevertheless, there has been limited research on the effect of proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) in UC patients treated with IFX and vedolizumab (VDZ). This study aimed to investigate the short-term efficacy of PR3-ANCA in patients with moderate-to-severe active UC. Methods A total of 191 patients with moderate to severe active UC were enrolled from January 2021 to January 2024 in three centers in this retrospective, multicenter, real-world, case-control study. Patients with PR3-ANCA were allocated to two groups based on the biologics regimen (IFX or VDZ). Additionally, UC patients without positive PR3-ANCA, who were matched for baseline covariates including age, sex, BMI, disease duration, disease location, Mayo endoscopic subscore(MES), and prior advanced therapies, were selected at a ratio of 1:3. Clinical remission (CRm) and response (CRs), and endoscopic response (ERs) and remission(ERm) at week 22 were the endpoints. Results Compared to UC patients with negative PR3-ANCA, those with positive PR3-ANCA had lower rates of CRm (47.44% vs. 23.08%, P = 0.029), ERs (57.69% vs. 34.62%, P = 0.041), and ERm (39.74% vs. 11.54%, P = 0.008), but similar rates of CRs (69.23% vs. 65.38%, P = 0.715). However, there are no significant differences in rates of CRm (30.00% vs. 29.82%, P = 0.986), CRs (63.33% vs. 63.16%, P = 0.987), ERs (33.33% vs. 35.09%, P = 0.870), and ERm (20.00% vs. 21.05%, P = 0.908) between VDZ-treated patients with positive PR3-ANCA and negative. Additionally, compared to VDZ-treated patients, those treated with IFX had similar rates in CRm (30.00% vs. 23.08%, P = 0.560), CRs (63.33% vs. 65.38%, P = 0.873), ERs (33.33% vs. 34.62%, P = 0.920), and ERm (20.00% vs. 11.54%, P = 0.481). Rates in CRm (47.44% vs. 29.82%, P = 0.039), ERs (57.69% vs. 35.09%, P = 0.009), and ERm (39.74% vs. 21.05%, P = 0.021) in IFX-treated patients with negative PR3-ANCA were significantly higher than those in the VDZ-treated patients, but CRs was similar (69.23% vs. 63.16%, P = 0.460). Conclusions Positive PR3-ANCA affects the efficacy of IFX rather than VDZ in patients with moderate to severe active UC. UC patients with positive PR3-ANCA results may benefit from the exploration of new treatment strategies.