Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study

• Published in: Digestive diseases and sciences Vol. 69; no. 5; pp. 1785 - 1792
• Main Authors: Carvalhas Gabrielli, Anna Maria, Ferretti, Francesca, Monico, Camilla Maria, Tombetti, Enrico, Maconi, Giovanni, Romeo, Samanta, Piazza O Sed, Nicole, Caprioli, Flavio, Mazzola, Anna Maria, Alicante, Saverio, Bertè, Roberto, Lolli, Elisabetta, Scribano, Maria Lia, Buscarini, Elisabetta, Ricci, Chiara, Carmagnola, Stefania, Ardizzone, Sandro, Cannatelli, Rosanna
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2024; Springer Nature B.V
• Subjects: Adult; Biochemistry; Colectomy - adverse effects; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - surgery; Endoscopy; Female; Gastroenterology; Hepatology; Humans; Inflammatory bowel disease; Italy - epidemiology; Janus Kinase Inhibitors - adverse effects; Janus Kinase Inhibitors - therapeutic use; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Performance evaluation; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - therapeutic use; Prospective Studies; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - therapeutic use; Remission (Medicine); Remission Induction; Steroids; Transplant Surgery; Treatment Outcome; Tumor Necrosis Factor Inhibitors - adverse effects; Tumor Necrosis Factor Inhibitors - therapeutic use; Italy; Inflammatory bowel disease; JAK-inhibitor; Surgery; Biologic therapy
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-024-08394-w

Background Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). Aims Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. Methods From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. Results We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 ( p  = 0.023) and W24 ( p  = 0.004), and with a higher partial Mayo score at W8 ( p  = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. Conclusions In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.