A new type of biologics called Janus kinase (JAK) inhibitors, which show promise in rheumatology treatment, are so new that many clinicians don’t know about them, Dr. John O’Shea recently told the American College of Rheumatology Daily News.
“The first member of this class, tofacitinib, was approved in 2012, but it’s a very fast-moving field with multiple new agents being studied,” said Dr. O’Shea, senior investigator at the National Institutes of Health’s molecular immunology and inflammation branch.
In his talk “Immunology Update: That’s a fact, Jak: Targeting Signaling Type I/II Cytokines in Rheumatic Diseases” at the 2016 ACR Annual Meeting in Washington, D.C., Dr. O’Shea discussed the promise JAK inhibitors appear to hold for treatment of rheumatic disease.
Where biologics tend to work like an on-off light switch, Dr. O’Shea encouraged attendees to think about JAK inhibitors in terms of a music switchboard, with which sound engineers can regulate a number of musicians and their levels at the same time.
“This is the way I’ve been thinking about therapy. Biologics, on-off switch. Jak inhibitors dial in. We have more sophisticated ability to dial in responses in a dose-dependent manner as long as we know what we are measuring,” he said. “If the sound engineers for our crummy little band have a board where there are 30 different switches, and they’re carefully modulating things, it really begs the question: why don’t we do that therapeutically?”
For the JAK inhibitors, which effectively involve some 20,000 switches, it’s a good deal more complicated than a small band. But the promise, Dr. O’Shea said, is a scenario down the road where drugs can be better tailored on a daily basis to patient needs.
Here’s the 10,000-foot view of how the JAK inhibitors work. Where other biologics try to block cytokines from binding to receptors on the surface of cells, to prevent them from causing further inflammation, JAK inhibitors prevent the spread of the process by blocking pathways within the cells themselves.
“It’s axiomatic in our business now that cytokines are key to the immunopathogenesis of the disease that we are interested in, but I would imagine for most of you, who don’t spend all day every day pondering cytokines, that it’s a little bit daunting that there’s probably 200 or so things that we call cytokines and how you keep track of them,” Dr. O’Shea said.
In the course of his research, Dr. O’Shea has also found that inhibiting the JAK-STAT pathway can also promote hair growth, beyond its immunological effects.
“Whether JAK inhibitors will be used in the future for male pattern baldness, I don’t know. But I can imagine everyone is thinking a lot about that,” he said. “I think it’s just a great idea. This may be my most important contribution to mankind here.”