Upadacitinib in Crohn’s disease

ABSTRACT

Introduction

The small molecule and oral selective and reversible Janus kinase (JAK) inhibitor upadacitinib has been approved for the treatment of moderate to severe active Crohn’s disease (CD) in adult patients since April 2023 by EMA/FDA.

Areas covered

The approval is based on the two induction studies a maintenance study showing that upadacitinib induction and maintenance therapy was superior to placebo. The approval of upadacitinib in CD expands the therapeutic armamentarium for the management of inflammatory bowel diseases (IBD). Upadacitinib is the first and only JAK inhibitor approved in patients with CD and provides a novel mechanism of action and the first advanced oral treatment option for patients with CD. Upadacitinib is approved for the treatment of other immunologically mediated disorders, including ulcerative colitis, rheumatoid arthritis, psoriasis arthritis, axial spondylarthritis, ankylosing spondylitis, and atopic dermatitis. Treatment of atopic dermatitis has been approved from the age of 12 years.

Expert opinion

Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn’s disease. Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD.

KEYWORDS:

• Janus kinase inhibitor
• small molecule
• upadacitinib
• Crohn’s disease
• STAT
• immune-mediated diseases
• treat to target
• mucosal healing

Article highlights

• Upadacitinib is the first approved jak inhibitor for the induction and maintenance treatment of moderate to severe active CD

• Upadacitinib provides a novel mechanism of action and the first advanced oral treatment option for patients with CD

• Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn’s disease

• More long-term data on the safety of upadacitinib are warranted

• Further clinical studies to assess the efficacy of upadacitinib for the treatment of fistulizing CD and extraintestinal manifestations are needed

• Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD

Declaration of interest

A Dignass has received consultancy fees from AbbVie, MSD, Ferring, Roche/Genentech, Takeda, Vifor, Falk, Janssen, Pfizer, Sandoz/Hexal, Celgene/BMS, Tillotts, Fresenius Kabi, Galapagos, Pharmacosmos, Novartis, Gilead, Arena, Celltrion, Lilly, Amgen, and Abivax; payment for lectures including service on speakers bureaus from Falk Foundation, Ferring, MSD, AbbVie, Vifor, Janssen, High5MD, Pfizer, Tillotts, Materia Prima, Galapagos, BMS, Takeda, and Sandoz; payment for manuscript preparation from Falk Foundation, Thieme, Takeda, Janssen, and Biogen.

P Esters received consultancy fees from AbbVie, Takeda, Janssen and Celltrion; payment for lectures including service on speakers bureaus from Falk Foundation, AbbVie, Vifor, Janssen, Takeda.

C Flauaus is an employee of AbbVie Deutschland GmbH & Co. KG and may own AbbVie stock.

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

A reviewer on this manuscript has disclosed they have received investigator-initiated funding from Janssen Canada, and served on advisory boards for AbbVie Canada, Sandoz Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Fresenius Kabi Canada, Biocon Canada, BMS Canada and Lilly Canada. They have also received grant support from Janssen Canada, and support for infrastructure from Abbvie Canada, Amgen Canada, Pfizer Canada, Takeda Canada and Sandoz Canada.

Abbvie provided a scientific accuracy review at the request of the journal editor.

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

Additional information

Funding

This paper was not funded.