A large clinical cohort study of adult patients taking JAK inhibitors for atopic dermatitis has found that they have more than twice the risk of developing acne at 6 months than patients taking Th2 cytokine inhibitors, providing clinical data that confirms findings from clinical trials.

“In clinical practice, 1 in 20 patients — 4.93% — who started upadacitinib or abrocitinib developed acne, and 1 in 26 — 3.9% — required prescription treatment for their acne,” lead study author Maria Schneeweiss, MD, a pharmacoepidemiologist in medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School in Boston, told Medscape Medical News. “This increase in the risk of acne in JAK inhibitor users was observed in both male and female sexes and across all age groups.”

Among the patients treated with a Th2 cytokine inhibitor, the risk for acne at 6 months was 1.96%.

The cohort study findings, published as a research letter in JAMA Dermatology, were from the ADVANCES system, a sequential monitoring system evaluating the safety of immune modulators to treat atopic dermatitis. The researchers used claims data from commercial insurers in the US along with Medicaid and Medicare fee-for-service programs collected from January 2017 to May 2025. After matching, the cohort included 2718 people taking the JAK inhibitors upadacitinib (2331) and abrocitinib (387), and 5404 on the Th2 cytokine inhibitors dupilumab (5207) and tralokinumab (197). The mean age of the patients was 42.6 years in both groups, and most patients started upadacitinib at 15 mg and abrocitinib at 100 mg; a few patients increased the dose.

“To our knowledge, this is the largest US-based study comparing patients with AD treated with JAK inhibitors to those receiving cytokine inhibitors in a clinical practice setting,” Schneeweiss said. “By utilizing claims data from a population-based cohort, our study reinforces the findings from clinical trials and expands their generalizability to dermatology practice.”

Study Results

The patients who started a JAK inhibitor had more than a twofold increased risk for acne over 6 months (relative risk, 2.51; 95% CI, 1.96-3.23) compared with those on a Th2 cytokine inhibitor.

Among the JAK inhibitor population, women had more than twice the risk for acne than men (6.4% vs 3%). The study also found the risk for folliculitis and rosacea was around 2% at 6 months in both the JAK inhibitor and Th2 cytokine inhibitor treatment groups. 

Patients who had previously used dupilumab before starting on a JAK inhibitor had an almost four times increased risk for acne than those on Th2 cytokine inhibitors (relative risk, 3.81; 95% CI, 2.99-4.86). The study found no meaningful difference in risk between tralokinumab and dupilumab, or abrocitinib and upadacitinib.

But Schneeweiss said the number of users was too small for a head-to-head comparison of the relative risk for acne between the two JAK inhibitors. “This agent-specific analysis warrants further analysis with updated data,” she said.

These are early data from the ADVANCES drug safety monitoring system, Schneeweiss noted. “As more patients use these medications, we will continue to follow this endpoint as well as several others,” she said. “In particular, we can get more robust results for the pairwise comparisons, such as upadacitinib vs abrocitinib.”

The research letter noted that the analysis did not include any data on high-dose JAK inhibitor use or the severity of atopic dermatitis and stated that physicians and patients should be aware of the risk for acne when starting low-dose JAK inhibitor therapy. 

“Acne is treatable but can be bothersome to patients, and it is thus material to discuss ahead of initiation of therapy,” Schneeweiss said. “Clinicians can better inform patients, leading to improved shared decision-making around which treatment is most appropriate for an individual.”

Real-World Findings

“This study helps move the conversation away from simply clinical trial signals to real-world dermatology practice,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University School of Medicine and Health Sciences in Washington, DC. “This analysis quantifies that risk in a large, commercially insured US population and compares it against a clinically relevant alternative, a biologic.”

“This study supports the current clinical observations that use of low-dose JAK inhibitors can promote the development of acne-like lesions in patients with atopic dermatitis,” Richard Gallo, MD, professor and chair of dermatology at the University of California, San Diego, said. “This provides evidence for dermatologists to counsel their patients on another risk of JAK inhibitors.”

Both Friedman and Gallo, who were not study authors, said the study population size and the nature of the comparative analysis were strengths.

However, they also noted limitations with the study. The claims-based data may have missed milder cases of acne and did not detail severity, Friedman told Medscape Medical News. “The study also lacks granular data on atopic dermatitis severity, morphology, or treatment discontinuation,” he said. “Additionally, most patients were treated with lower starting doses of JAK inhibitors, so the findings may not fully capture risk at higher doses or in more refractory disease.”

Gallo concurred that the lack of information on acne at higher doses is a limitation. 

“The most practical takeaway is that acne — or ‘JAKne’ — is a real and relatively common early adverse event with JAK inhibitors in atopic dermatitis, occurring within the first 6 months of therapy and at a higher rate than with biologic Th2 pathway inhibitors,” Friedman added. “This risk appears particularly relevant for younger adults and women.”

For clinicians, acne should be part of routine counseling when starting patients on a JAK inhibitor, Friedman said, “not as a reason to avoid therapy, but as something to anticipate, monitor, and manage proactively.

“Importantly, the absence of increased rosacea or folliculitis suggests that not every papulopustular eruption in these patients should be automatically labeled as ‘JAKne,’ reinforcing the need for thoughtful clinical assessment,” he noted.

Schneeweiss reported receiving grants from UCB. Friedman reported having financial relationships with Regeneron, Lilly, Pfizer, and AbbVie. Gallo reported having no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in Philadelphia.