The Optimal Use and Future Use of JAK Inhibitors in IBD

Janus kinase (JAK) inhibitor treatment for the management of IBD can be safe and effective, and work rapidly, but clinicians should take care to adequately screen patients before initiating therapy, Marla Dubinsky, MD, said during her presentation on the “Optimal Use and Future Use of JAK Inhibitors for the Management of IBD” at the Advances in Inflammatory Bowel Disease virtual regional meeting on August 7.

Dr Dubinsky is the codirector of Susan and Leonard Feinstein IBD Clinical Center at the Icahn School of Medicine at Mount Sinai Hospital in New York City.

Dr Dubinsky opened the presentation detailing the consequence of JAK inhibition on signaling by key immunoregulatory cytokines. “By focusing on the selective JAK-1 inhibitors, you’ll be able to get an appreciation of what are the various cytokine targets that these therapies approach,” she explained.

She reviewed the OCTAVE study of the JAK inhibitor tofacitinib, which involved 2 placebo-controlled induction studies and had a primary endpoint of mucosal healing at week 8. Dr Dubinsky posed the question of whether there were differences in outcomes based on TNF exposure. “You know there is a lot of discussion around sequencing, and what kind of patients—if they fail TNFs, would they be better candidates for one therapeutic target over another?” Dr Dubinsky said. “What you need to focus on is what is actually the delta, meaning the difference between the active comparator arm, vs placebo, and the delta arm between these is actually quite similar, whether you were a failure or not a failure.”

She added, “Another thing that was interesting and we had not seen before, was for patients that went into a second 8-week induction.” Extending the induction dose for another 8 weeks of tofacitinib therapy for patients who displayed an inadequate response at week 8 of OCTAVE induction 1 and 2 proved some patients may need a little longer to show adequate response to the therapy, Dr Dubinsky explained.

“Since these drugs work so quickly, in my opinion, personally, I don’t wait that long to decide if a patient needs to go on to something else; I think it depends on the patient. Because the patient wants to get better,” she said.

Dr Dubinsky also highlighted the importance of understanding a patient’s potential underlying risk factors, and stressed the value of clinicians asking the right questions in determining the drug a patient needs—including the risk of infections, and understanding where these issues occur during the treatment process.

Dr Dubinsky also highlighted tofacitinib’s safety data in ulcerative colitis (UC), explaining that “UC patients treated with tofacitinib on average were younger (45 years vs 60 years), and more likely to be males. Tofacitinib safety appears to be similar between rheumatoid arthritis and UC, and gastrointestinal adverse events are elevated, which is expected given the study population.”

Dr Dubinsky compared other studies of JAK inhibitors, comparing remission, response, and endoscopic improvement.

“Some considerations before initiating JAKs should include screening for tuberculosis; remember to get your baseline labs; measuring lymphocytes, neutrophils, hemoglobin, lipids, and hepatic enzymes; susceptibility to viral hepatitis, and serious or opportunistic infections; ensure all immunizations are up to date,” Dr Dubinsky summarized. “And don’t forget to assess for cardiovascular risk factors, as we are starting to understand the risks of cardiac events.”

—Angelique Platas

Dubinsky M. Optimal use and future use of JAK inhibitors for the management of IBD. Presented at: Advances in Inflammatory Bowel Disease regional meeting. August 7, 2021. Virtual.