What is a JAK Inhibitor?
These new autoimmune medications are poised to hit the market after two decades of research, offering new IBD treatment options to Crohn’s and colitis patients.
The Discovery of JAK and its Effects on the Immune System
About 20 years ago, a new enzyme family was discovered by pharmaceutical researchers: the Janus Kinases, or JAK. Researchers found that this family of enzymes forms an essential part of a signalling pathway that triggers the production of cytokines, or immune cells.
Researchers hypothesized that altering the activity of the JAK enzymes would ultimately modify the body’s immune response—and they were right. Because autoimmune diseases like Crohn’s disease and ulcerative colitis are characterized by a chronic, inflammatory immune response, medications that interfere with immune response mechanisms in the body have been a main focus of autoimmune research and development during recent years.
Today, several pharmaceutical companies are developing new medications for treating autoimmune diseases based on the discovery of the JAK enzyme family and the role they play in activating the immune system. These drugs are called JAK inhibitors, and they work by inhibiting the JAK signalling pathway, diminishing the cytokine activity that corresponds with an immune and inflammatory response.
JAK Inhibitors for IBD
A number of JAK inhibitor medications are approved for clinical use in the treatment of rheumatoid arthritis, psoriasis, bone marrow cancer, eczema, and several other conditions. Researchers are studying JAK inhibitors as treatment for inflammatory bowel disease (IBD), with several medications in the final stages of clinical trials.
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Biopharmaceutical company Pfizer first got FDA approval for their JAK inhibitor Tofacitinib (brand name XELJANZ) in 2012 for the treatment of rheumatoid arthritis. In May 2018, the FDA announced the approval of XELJANZ for the treatment of moderate to severe ulcerative colitis (UC) in adults, making it the first oral medication approved for long-term use as a UC treatment.
AbbVie, a pharmaceutical company headquartered in Illinois, is investigating JAK inhibitor Upadacitinib as an IBD treatment. It is currently in Phase 3 trials for moderate to severe Crohn’s disease and in patients who haven’t had success with other common IBD therapies, such as immunomodulators or anti-TNFs.
In February of this year, AbbVie announced positive results from an extension of their Phase 2 CELEST study, showing that the patients who had achieved remission during the 4-month CELEST study on Upadacitinib maintained remission throughout the next 9 months.
Research centers are currently recruiting for Upadacitinib Phase 3 clinical trials—learn more about Upadacitinib in our Discover Therapies resources, or take a short quiz on the Discover Therapies to see if you’re eligible to participate in IBD clinical trials.
JAK inhibitor filgotinib being developed by pharmaceutical company Galapagos, partnering with Gilead to bring the medication through clinical trials.
Filgotinib is being examined as both a Crohn’s disease medication and UC therapy. Phase 2 trials tested the drug as a treatment for small bowel Crohn’s disease and fistulizing Crohn’s disease. Phase 3 trials are ongoing, and research teams are actively recruiting participants for clinical trials for filgotinib.
Benefits of JAK Inhibitors
These new medications are thought to have several advantages over conventional biologic IBD treatments.
While biologics require injection or infusion treatments, JAK inhibitor medications benefit from a smaller molecular size, which allows for oral administration—good news for IBD patients who’d prefer a more convenient IBD treatment (not to mention, less painful).
JAK inhibitors are not only projected to be less expensive than biologics, but they also present an entirely new alternative treatment for Crohn’s and colitis patients who have had failed biologic therapy.
Furumoto, Y., & Gadina, M. (2013). The arrival of JAK inhibitors: advancing the treatment of immune and hematologic disorders. BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy, 27(5), 431–438. http://doi.org/10.1007/s40259-013-0040-7
L.C.S. De Vries, M.E. Wildenberg, W.J. De Jonge, G.R. D’Haens; The Future of Janus Kinase Inhibitors in Inflammatory Bowel Disease, Journal of Crohn's and Colitis, Volume 11, Issue 7, 1 July 2017, Pages 885–893, https://doi.org/10.1093/ecco-jcc/jjx003