Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors

ABSTRACT

Introduction

Janus kinase (JAK) inhibitors are an emerging class of small-molecule drugs, providing targeted therapy for a variety of diseases, and have made their way into the treatment of armamentarium of ulcerative colitis (UC) in recent years.

Areas covered

This review focuses on the pharmacokinetics, safety, and efficacy of selective JAK1 inhibitors in the treatment of moderate-to-severe UC. The PubMed database and clinicaltrials.gov were consulted using keywords – further expanded in the methods section. The search was focused on full-text publications in English. No publication date restrictions were imposed.

Expert opinion

JAK1 inhibitors are small-molecule drugs used in the treatment of ulcerative colitis and other immune mediated inflammatory diseases. They are orally bioavailable and have a rapid mechanism of action and no immunogenicity. JAK inhibitors can be used for the management of both naïve patients and biological-experienced patients.

Particular attention should be paid to elderly patients or those with cardiovascular or oncological risk factors, in whom JAK inhibitors should be recommended only if no alternatives are available. In addition, JAK inhibitors have the potential to be combined with other biological drugs or small molecules for the management of difficult-to-treat cases.

KEYWORDS:

• Filgotinib
• Upadacitinib
• ivarmacitinib
• JAK1
• ulcerative colitis

Article highlights

• This drug class could potentially be used in advanced dual therapy, in combination with biologics to enhance induction of remission

• JAK1 inhibitors show promise in treatment of UC but further evaluation is needed to determine their long-term safety and efficacy

• JAK inhibitors dampen the effect of multiple proinflammatory cytokines

• They are orally administered, have a rapid onset of action and no immunogenicity

Declaration of interest

F D’Amico served as a speaker for Sandoz, Jannsen, Omega Pharma, and Galapagos and served as an advisory board member for Galapagos. F Furfaro received consulting fees from Amgen, AbbVie and lecture fees from Janssen and Pfizer; M Allocca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, AbbVie and Pfizer; G Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. L Peyrin-Biroulet declares personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, Pandion Therapeutics, Gossamer Bio, Viatris, Thermo Fisher; grants from AbbVie, MSD, Takeda, Fresenius Kabi; stock options: CTMA; S Danese served as a speaker, consultant, and advisory board member for Schering-Plow, Abbott (AbbVie) Laboratories, Merck, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

S Danese conceived the study. A Goetsch and F D’Amico wrote the article and created tables and figures. M Allocca, G Fiorino, F Furfaro, A Zilli, T L Parigi, L Peyrin-Biroulet, and S Danese critically revised the manuscript. The manuscript was approved by all authors.

Additional information

Funding

This paper was not funded.