The JAK Inhibitor Safety Conversation

The arrival of Janus kinase (JAK) inhibitors has been among the most catalyzing events to occur in dermatology pharmaceuticals. Among the most efficacious agents ever assessed and approved to treat common conditions like atopic dermatitis and psoriasis—as well as contributory to treatment breakthroughs in vitiligo and alopecia areata—JAK inhibitors are a key tool in the increasingly robust armamentarium of targeted therapies today.¹

What’s more, the drug class is safer than would-be patients are led to believe, argues at least one expert.

In the first segment of an interview with HCPLive during the Society for Dermatology Physician Assistants (SDPA) 2024 Summer Meeting, Matthew Zirwas, MD, director of the clinical trials and dermatitis center at Dermatologists of Greater Columbus, discussed his planned presentation on the subject of reviewing JAK inhibitor safety with patients. The basis of the talk at SDPA Summer 2024 was centered around the matter of the US Food and Drug Administration (FDA)’s required boxed warning for JAK inhibitors including upadacitinib (Rinvoq) and baricitinib (Olumiant), regarding their apparent risk of serious major adverse cardiovascular events (MACE), blood clots, and cancer in treated patients.²

“My belief fully—and it's based on an enormous amount of literature—is that there is zero MACE risk, there's zero VTE risk, cancer risk, risk of death—all of the things in the box warnings—we have really strong evidence to say that those things are not risks at all,” Zirwas said. “So, I'm going to be going through some of that evidence, as well as how I talk to patients, because it is such a crucial thing.”

Zirwas said the topic is a very frequent and pivotal one among his patients who would be eligible for JAK inhibitors—one that which requires a more substantial, evidence-based response than simply replying, “Just trust me.”

“You've got to have almost a script that you're ready to use, and you have to know the rationale behind that script, so that if the patients then ask you questions, you're ready to go with them,” Zirwas said. “And that's what I'm really gonna be focusing on, is really helping people understand how safe these drugs are and second, how to have a very brief...one-minute conversation with the patient about the box warning.”

In previewing his own script in the physician-patient discussion, Zirwas said he very specifically tells his patients, “All of the data have shown no risk.” Often, a patient will reply asking, “So, it’s been proven that there’s no risk of heart attacks, strokes, or blood clots?” The correct answer, Zirwas said, is no—it has not been proven.

“But it also hasn't been proven that doxycycline doesn't cause cancer, right?” Zirwas said. “There's not been a 10-year safety study of taking doxycycline and seeing does it change your intestinal microbiome and put you more at risk for colorectal cancer. That is possible.”

Rather, Zirwas explains to his patients that data worth 20,000 treated patients has not shown a discernible risk with the JAK inhibitors in question. Whether the risk is possible, Zirwas explained, is a different subject altogether.

“And some patients will be like, 'I get it.' Other patients are like, 'Well, if there's any chance that it might increase the risk of any of those things, I don't want to take it.' Okay, fine. I mean, I can't tell you absolutely it's been proven there's no risk. So that just means okay, we're not going to use that medication yet—let's talk about what the other options are,” Zirwas said.

References

1. ^{Alicea J. Brett King, MD, PhD: The Promise of Janus Kinase Inhibitors. HCPLive. Published July 26, 2021. https://www.hcplive.com/view/the-promise-of-janus-kinase-inhibitors}
2. ^{FDA. Janus Kinase (JAK) inhibitors: Drug Safety Communication - FDA Requires Warnings about Increased Risk of Serious Heart-related Events, Cancer, Blood Clots, and Death. Web page. Published February 25, 2019. Last updated September 1, 2021. Accessed June 10, 2024. https://www.fda.gov/safety/medical-product-safety-information/janus-kinase-jak-inhibitors-drug-safety-communication-fda-requires-warnings-about-increased-risk}