JAK inhibition in inflammatory bowel disease.
Current available treatments for inflammatory bowel disease (IBD) have some limitations and new options are needed. Several new molecules are being tested for the treatment of IBD and other immune-mediated inflammatory diseases. Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF naïve and anti-TNF experienced patients. Other compounds with JAK inhibitory activity are also being tested with promising results. Areas covered: This review discusses the molecular aspects of the JAK-STAT pathway, which gives rationale for the use of JAK inhibitors in immune-mediated inflammatory diseases, especially in IBD. Different compounds with JAK inhibitory activity are presented, and relevant efficacy and safety data in IBD and other conditions are discussed. Expert commentary: It would not be surprising that in a foreseeable future many new orally administrated drugs will be available. This enhanced armamentarium will probably pose new dilemmas, in terms of drug positioning, escalation and de-escalation strategies, and combination therapy.
a Gastroenterology Section, Department of Internal Medicine , Centro de Educación Médica e Investigaciones Clínicas (CEMIC) , Buenos Aires , Argentina.|b INSERM U954 and Department of Hepatogastroenterology , Nancy University Hospital, Université de Lorraine , Vandoeuvre-lès-Nancy , France.
Pablo
P
Olivera
c Department of Gastroenterology , IBD Center, Humanitas Clinical and Research Center , Milan , Italy.
Silvio
S
Danese
b INSERM U954 and Department of Hepatogastroenterology , Nancy University Hospital, Université de Lorraine , Vandoeuvre-lès-Nancy , France.
Laurent
L
Peyrin-Biroulet
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D018570:Risk Assessment; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D050791:STAT Transcription Factors; C479163:tofacitinib; D053612:Janus Kinases
Crohn’s disease; Inflammatory bowel disease; JAK inhibitors; small molecules; tofacitinib; ulcerative colitis