Critical Appraisal of Filgotinib in the Treatment of Ulcerative Colitis: Current Evidence and Place in Therapy

Abstract

Arianna Dal Buono,1 Roberto Gabbiadini,1 Virginia Solitano,1,2 Edoardo Vespa,1,2 Tommaso Lorenzo Parigi,1,2 Alessandro Repici,2,3 Antonino Spinelli,1,2,4 Alessandro Armuzzi1,2 1IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 3Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 4Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Rozzano, Milan, ItalyCorrespondence: Alessandro Armuzzi, IBD Center, Humanitas Research Hospital – IRCCS, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Rozzano, Milan, Italy, Tel [phone], Fax [phone], Email [email protected] and Aims: Patients affected by moderate-to-severe Ulcerative Colitis (UC) demand a challenging management. Small molecules, administrated as oral agents, have the ambition of overcoming the limitations of the biologic agents (ie, parenteral administration, rapidity of action, primary and secondary non-responsiveness). Beyond tofacitinib, a pan-Janus kinase (JAK) inhibitor already approved for the treatment of moderate-to-severe UC, novel more selective molecules like filgotinib are being currently evaluated in randomized clinical trials. We aimed to review the current evidence on filgotinib, a JAK-1 preferential inhibitor, in the treatment of UC and its place in therapy in the current scenario.Methods: PubMed and EMBASE were searched to identify relevant studies: those investigating the efficacy and safety of filgotinib in the treatment of UC patients were included in this narrative review.Results: The current preliminary data have shown that filgotinib is safe and effective in inducing clinical end endoscopic response in both biologic-naïve and biologic-experienced patients with moderate-to-severe UC, also with high inflammatory burden at baseline. In the SELECTION trial, one case of pulmonary embolism occurred with filgotinib 200 mg induction, and three venous thrombosis cases were observed in the placebo maintenance/LTE; the incidence of herpes zoster was ≤ 1% in all UC treated patients. Filgotinib represents an appealing treatment option for its high selectiveness, route of administration and rapidity of action; cost-effectiveness studies and head-to-head trials are needed to better define its place in therapy.Keywords: ulcerative colitis, filgotinib, Janus kinase inhibitors, efficacy, safety

Keywords

• ulcerative colitis
• filgotinib
• janus kinase inhibitors
• efficacy
• safety.