JAK Inhibitors Tied to Increased Risk of Herpes Zoster in IBD, Other Immune-Mediated Diseases

By Marilynn Larkin

January 28, 2020

NEW YORK (Reuters Health) - Patients with inflammatory bowel disease (IBD) or other immune-mediated conditions may be at increased risk of herpes zoster infection if treated with Janus kinase (JAK) inhibitors, a systematic review and meta-analysis suggests.

Dr. Laurent Peyrin-Biroulet of Lorraine University in Vandoeuvre-les-Nancy, France, and colleagues investigated the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, and ankylosing spondylitis by searching the literature from 1990 through 2019.

As reported in Gastroenterology, 82 studies (two-thirds, randomized controlled trials) involving 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor were included in the final analysis.

The overall incidence rate of adverse events (AEs) was 42.65 per 100 person-years; for serious AEs, the rate was 9.88.

Incidence rates for specific AEs were: serious infections, 2.81 per 100 person-years; herpes zoster, 2.67; malignancy, 0.89; and major cardiovascular events, 0.48.

Mortality was no higher in patients treated with JAK inhibitors than for those who received placebo or an active comparator (relative risk, 0.72). JAK inhibitor use conferred a significantly increased risk of herpes (RR, 1.57), but not other AEs.

Two gastroenterologists not involved in the study commented in emails to Reuters Health.

Dr. Lisa Malter, a gastroenterologist and associate professor of medicine at NYU Langone Health in New York City, said "This meta-analysis confirms what we know already regarding risk of zoster. The only FDA-approved JAK inhibitor in IBD is tofacitinib, which has been available for use in moderate to severe ulcerative colitis since May 2018."

"The noted signal for increased risk of herpes zoster has led to a recommendation that patients be vaccinated with the inactivated Shingrix vaccine regardless of age if they are prescribed this agent," she said. "It can sometimes be difficult to obtain insurance coverage, given the US Centers for Disease Control and Prevention recommendation that only people over 50 receive this vaccine."

"In addition, due to concern for an increased risk in thrombotic events with tofacitinib (seen in rheumatoid arthritis patients with underlying cardiovascular disease), labeling was changed in 2019, and now requires patients fail an anti-TNF agent prior to being prescribed this drug," she said. "Overall, this medication is never a first-line agent to treat IBD due to its risk profile."

Dr. Ryan Ungaro, assistant professor at the Susan and Leonard Feinstein IBD Center at Icahn School of Medicine at Mount Sinai, also in New York City, said, "This study helps confirm what we have observed clinically and from studies on tofacitinib for ulcerative colitis." Like Dr. Malter, he noted that patients should be vaccinated prior to or near start of treatment.

"As with any medication, the true risk profile for adverse events can take years of real-world use to be fully understood," he said. "Most data in this study were from randomized, controlled trials, which are relatively shorter term and with carefully selected patient population. So I think we will need further data in coming years, especially on serous infection and cancer risk."

"For physicians treating IBD patients, it will be interesting to see if zoster risk is seen in other more selective JAK inhibitors, which will likely become available for IBD treatment in the coming years," he added.

Regarding the black box warning for venothromboembolism, he noted, "I think we still need further data, especially in the IBD population, to completely understand the magnitude of this risk and how it manifests specifically in IBD patients."

Dr. Peyrin-Biroulet declined to provide a comment.

SOURCE: http://bit.ly/2TT8nRG Gastroenterology, online January 2, 2020.