Comparative Persistence of Non-tumor Necrosis Factor (TNF) vs. TNF Antagonists for Post-operative Prophylaxis in Crohn’s Disease (CD)

• Published in: Digestive diseases and sciences Vol. 69; no. 1; pp. 235 - 245
• Main Authors: Gu, Phillip, Dube, Shishir, Lee, YooJin, Yang, Shaohong, Li, Dalin, Haritunians, Talin, Vasiliauskas, Eric, Bonthala, Niru, Syal, Gaurav, Yarur, Andres, Ziring, David, Targan, Stephan, Rabizadeh, Shervin, Melmed, Gil Y., Fleshner, Phillip, McGovern, Dermot P. B.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2024; Springer Nature B.V
• Subjects: Biochemistry; Crohn Disease - drug therapy; Crohn Disease - prevention & control; Crohn Disease - surgery; Crohn's disease; Disease prevention; Endoscopy; Gastroenterology; Hepatology; Humans; Medicine; Medicine & Public Health; Necrosis; Oncology; Original; Original Article; Prospective Studies; Retrospective Studies; Transplant Surgery; Tumor Necrosis Factor Inhibitors - adverse effects; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Post-operative prophylaxis; Comparative effectiveness; Post-operative recurrence; Drug persistence; Crohn’s disease
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-023-08192-w

Background The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohn’s disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR). Methods We conducted a single-center, retrospective study of surgically naïve CD subjects undergoing ileocecal or small bowel resection between 1/1/2000 and 12/31/2021 and prescribed a biologic for post-operative prophylaxis. We compared the risk of prophylaxis failure (requiring recurrent surgery or discontinuation of therapy due to persistent POR despite optimized drug level or dose escalation, immunogenicity, and/or adverse event) and early endoscopic POR (Rutgeert’s score ≥ i2 within 15 months postoperatively) between non-TNF and TNF antagonist prophylaxis using Cox proportional hazard and logistic regression, respectively, adjusting for demographic and disease characteristics. Results The study included 291 subjects (81% TNF antagonists). After multivariable adjustment, non-TNF antagonist prophylaxis was associated with a significantly lower risk of prophylaxis failure than TNF antagonists (hazard ratio 0.26; 95% confidence interval (CI) [0.13–0.53]). Prophylaxis with non-TNF and TNF antagonists had similar risk of early endoscopic POR (odds ratio 0.66; 95% CI [0.32–1.36]). Stratifying the non-TNF antagonists by anti-integrin and anti-IL12/23 yielded similar results. Conclusion In a cohort of surgically naïve CD subjects prescribed a biologic for post-operative prophylaxis, non-TNF antagonists had greater persistence than TNF antagonists with similar risk for early endoscopic POR. If confirmed by large, prospective studies, these findings can inform post-operative management strategies in CD.