JAK inhibitors for inflammatory bowel disease: recent advances

Sailish Honap; Alexandra Agorogianni; Michael Colwill; Sonia Kalyanji Mehta; Fiona Donovan; Richard  Pollok; Andrew Poullis; Kamal  Patel

doi:10.1136/flgastro-2023-102400

JAK inhibitors for inflammatory bowel disease: recent advances

Sailish Honap^*, Alexandra Agorogianni, Michael Colwill, Sonia Kalyanji Mehta, Fiona Donovan, Richard Pollok, Andrew Poullis, Kamal Patel

^*Corresponding author for this work

King's College London

Research output: Contribution to journal › Review article › peer-review

23 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn’s disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.

Original language	English
Article number	23102400
Pages (from-to)	59-69
Number of pages	11
Journal	Frontline Gastroenterology
Volume	15
Issue number	1
Early online date	14 Sept 2023
DOIs	https://doi.org/10.1136/flgastro-2023-102400
Publication status	Published - 14 Sept 2023

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10.1136/flgastro-2023-102400

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title = "JAK inhibitors for inflammatory bowel disease: recent advances",

abstract = "Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn{\textquoteright}s disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.",

author = "Sailish Honap and Alexandra Agorogianni and Michael Colwill and {Kalyanji Mehta}, Sonia and Fiona Donovan and Richard Pollok and Andrew Poullis and Kamal Patel",

note = "Funding Information: Marketing authorisation for upadacitinib in CD was supported by the results of the 12-week induction studies (U-EXCEL and U-EXCEED) including 1021 patients, and a 52-week maintenance study (U-ENDURE) of 502 patients. 33 Three-quarters of patients had prior biological failure. The coprimary endpoints of clinical remission and endoscopic response were assessed at weeks 12 and 52. For induction, the proportion of patients in remission was nearly twice as high with upadacitinib compared with placebo and at least three times as high for endoscopic response. For maintenance, the delta above placebo was 2-3 fold higher for remission versus placebo and almost six times higher for endoscopic response (table 2). Differences of this magnitude have not been seen in prior registration CD trials. Funding Information: SH has served as a speaker, a consultant and/or advisory board for Pfizer, Janssen, Abbvie and Takeda, has received educational grants from Dr. Falk Pharma, Pharmacosmos and Ferring, and has had research supported by Pfizer. SKM has received speaker fees and/or advisory board fees from Dr. Falk Pharma. KP has received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, Dr. Falk Pharma, PredictImmune, Pfizer and Ferring and has received advisory board fees from Abbvie, Galapagos, Pfizer, and Janssen. AA, MJC, FD, RP and AP report no conflicts. Publisher Copyright: {\textcopyright} 2023 BMJ Publishing Group. All rights reserved.",

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doi = "10.1136/flgastro-2023-102400",

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AU - Honap, Sailish

AU - Agorogianni, Alexandra

AU - Colwill, Michael

AU - Kalyanji Mehta, Sonia

AU - Donovan, Fiona

AU - Pollok, Richard

AU - Poullis, Andrew

AU - Patel, Kamal

N1 - Funding Information: Marketing authorisation for upadacitinib in CD was supported by the results of the 12-week induction studies (U-EXCEL and U-EXCEED) including 1021 patients, and a 52-week maintenance study (U-ENDURE) of 502 patients. 33 Three-quarters of patients had prior biological failure. The coprimary endpoints of clinical remission and endoscopic response were assessed at weeks 12 and 52. For induction, the proportion of patients in remission was nearly twice as high with upadacitinib compared with placebo and at least three times as high for endoscopic response. For maintenance, the delta above placebo was 2-3 fold higher for remission versus placebo and almost six times higher for endoscopic response (table 2). Differences of this magnitude have not been seen in prior registration CD trials. Funding Information: SH has served as a speaker, a consultant and/or advisory board for Pfizer, Janssen, Abbvie and Takeda, has received educational grants from Dr. Falk Pharma, Pharmacosmos and Ferring, and has had research supported by Pfizer. SKM has received speaker fees and/or advisory board fees from Dr. Falk Pharma. KP has received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, Dr. Falk Pharma, PredictImmune, Pfizer and Ferring and has received advisory board fees from Abbvie, Galapagos, Pfizer, and Janssen. AA, MJC, FD, RP and AP report no conflicts. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

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N2 - Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn’s disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.

AB - Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn’s disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.

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DO - 10.1136/flgastro-2023-102400

M3 - Review article

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SP - 59

EP - 69

JO - Frontline Gastroenterology

JF - Frontline Gastroenterology

IS - 1

M1 - 23102400

ER -

JAK inhibitors for inflammatory bowel disease: recent advances

Abstract

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