VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.
“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.
Ted Bosworth/Medscape Medical News
Romain Aymon
This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.
The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.
“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.
Dr. Floris A. van Gaalen
“It is nice to have data indicating that risk of other infections is no higher with JAKi than other treatment options, but I am not sure this has been a big concern,” he said. “But I do think more information about other types of risks would be helpful.”
Relative Risk for Infection on JAKi Is Unclear
Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.
The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.
Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.
For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.