Predictive factors for primary nonresponse to biologics in ulcerative colitis: a prospective multicenter study

We sought to evaluate the predictive value of protease-3 (PR3)-anti-neutrophil cytoplasmic antibodies (ANCAs) and myeloperoxidase (MPO)-ANCA for primary nonresponse (PNR) to biologic agents in patients with ulcerative colitis (UC).

A multicenter, prospective cohort study was conducted. Patients with UC who initiated biologic agents (anti-TNF, anti-integrin, or anti-IL12/23 agents) as their first-line therapy were enrolled. PNR was defined as failure to achieve a partial Mayo Score improvement of at least 2 points by weeks 14-16 or necessitating treatment modification. Logistic regression identified PNR predictors.

Among 95 biologic-naïve UC patients, 38 received anti-TNF, 39 received anti-integrin, and 18 received anti-IL12/23 agents. PR3-ANCA positivity was observed in 47.4% of anti-TNF recipients. The PNR rate among PR3-ANCA-positive patients receiving anti-TNF therapy was 66.7%, significantly higher than in PR3-ANCA-negative patients (25.0%, P = 0.02). Multivariate logistic regression confirmed PR3-ANCA as an independent risk factor for PNR to anti-TNF therapy (OR 5.61; 95% CI 1.37-26.82; P = 0.02). By contrast, PR3-ANCA did not predict PNR to anti-integrin therapy, but the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammatory index (SII) were identified as significant predictors. Only one of 95 patients tested positive for MPO-ANCA, precluding statistical analysis for its association with PNR.

In patients with UC, PR3-ANCA is a significant predictor of PNR to anti-TNF therapy, but not to anti-integrin therapy. PLR and SII may predict PNR to anti-integrin therapy. PR3-ANCA could aid biologic selection, optimizing personalized UC treatment and healthcare resource utilization.