Upadacitinib for the Treatment of Moderate-to-Severe Crohn’s Disease

Abstract

Despite an increasing number of therapies for Crohn’s disease (CD), half of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. Inhibition of Janus kinases (JAKs) has emerged as an important therapeutic target for CD. Upadacitinib is an orally administered selective JAK1 inhibitor, which is effective for the induction and maintenance of remission in moderately-to-severely active CD, including in patients with prior failure of biological therapy. Nonselective JAK inhibition has been associated with thromboembolic disease, cardiovascular events and malignancy in patients older than 50 years with rheumatoid arthritis and pre-existing cardiovascular risk factors, which should be considered upon prescription. Upadacitinib is the first and currently only oral advanced therapy for CD.

Plain language summary

Not all patients with Crohn’s disease (CD) get better with treatment. Blocking Janus kinases (JAKs), enzymes that promote inflammation in the gut, could help these patients. The treatment upadacitinib blocks JAK1 (an enzyme transmitting inflammatory signals) and decreases inflammation in the gut. It eases symptoms. It also resolves gut inflammation in patients with CD. Regarding side effects, JAK inhibitors can cause blood clots in veins, and in the lungs, heart attacks, cancer and infections. Further studies are needed, but caution is advised. Upadacitinib is the first advanced therapy for CD given by mouth.

Tweetable abstract

Upadacitinib is the first and currently only oral advanced therapy for Crohn’s disease (CD), which is effective for the induction and maintenance of remission in moderately-to-severely active CD, including in patients with prior failure of biological therapy.

Keywords::

• advanced therapy
• clinical trials
• inflammatory bowel disease
• Janus kinase
• small molecule

Author contributions

Conception and design: J Hanzel, C Ma and V Jairath. Manuscript drafting: J Hanzel and V Jairath. Manuscript editing for important intellectual content: J Hanzel, C Ma and V Jairath. All authors approved the final version of this manuscript for submission.

Financial disclosure

J Hanzel has received consulting fees from Alimentiv Inc.; and speaker’s fees from Abbvie, Janssen and Takeda. C Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda and Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer and Takeda; royalties from Springer Publishing; research support from AbbVie, Ferring and Pfizer. V Jairath has received consulting/advisory board fees from AbbVie, Alimentiv Inc., Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx and Vividion; and speaker’s fees from Abbvie, Ferring, Galapagos, Janssen, Pfizer, Shire, Takeda and Fresenius Kabi. 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.