Major Risk Factors Identified Which May Limit Oral JAK Inhibitor Use in HS

Only 17.7% of patients with hidradenitis suppurativa (HS) have no risk factors for oral Janus Kinase inhibitor (JAKi) use, new findings suggest, with top risk factors including smoking, obesity, hypertension, and hyperlipidemia.1

These data resulted from new research conducted to expand upon existing knowledge of risk factors which can limit JAKi efficacy. The study’s investigators highlighted that effective recalcitrant HS therapies are somewhat lacking, highlighting the novel oral JAK inhibitor approach that has emerged as a potential treatment option.

This study was led by Ditte Georgina Zhang, a PhD candidate from Copenhagen University Hospital’s Department of Dermato-Venereology & Wound Healing Centre.

“As these risk factors are common in patients with HS, the suitability for oral JAKi treatment is uncertain,” Zhang and colleagues wrote. “This study aims to assess the prevalence of risk factors that may limit the appropriateness of oral JAKi use in patients with HS.”1,2

Evaluating Risk Factors Limiting Oral JAK Inhibitors for HS

Both a clinical patient cohort drawn from the Copenhagen Hidradenitis Suppurativa Cohort (CHSC) and a questionnaire-based patient cohort drawn from the Danish Skin Cohort (DSC) were used by the investigators as 2 separate groups with HS to evaluate in their analysis.

The investigative team assessed the prevalence of both modifiable and non-modifiable risk factors within each of the 2 cohorts. The team did this individually and also pooled the data to generate combined estimates. A notable addition to the study was a re-evaluation of patients from the Danish Skin Cohort at the 12-month follow-up who did not have identified risk factors during their evaluation at baseline.

The investigators’ analysis involved 1,654 subjects in total, with 769 participants having been featured in the Copenhagen Hidradenitis Suppurativa Cohort and 885 in the Danish Skin Cohort. They highlighted the median body mass index (BMI) of subjects in either arm of the study, which was noted as 27.9 kg/m² (IQR: 23.8–32.5) among those in the Copenhagen Hidradenitis Suppurativa Cohort cohort and 29.7 kg/m² (IQR: 25.6–35.0) among those in the Danish Skin Cohort.

The median age in the Danish Skin Cohort cohort was noted as 48.0 years (IQR: 38.2–56.2), whereas those in the Copenhagen Hidradenitis Suppurativa Cohort had a median age of 39.8 years (IQR: 28.0–50.8). The team highlighted substantial variance in severity of HS between the 2 groups in the study, pointing to mild disease among 51.3% of those in the Copenhagen Hidradenitis Suppurativa Cohort and 41.4% of those included in the Danish Skin Cohort participant group. They further noted moderate disease in 29.2% and 32.4%, and severe disease in 19.5% and 26.3%, respectively.

In looking at the most common risk factors among subjects, the research team highlighted smoking as the most common (43.9%), then obesity (41.8%), hypertension (34.0%), hyperlipidemia (31.9%), and diabetes (12.9%). They found that 17.7% of patients in either group had no risk factors that would lead to questions on the suitability of implementing oral JAKi.

The team further noted that 30.2% maintained a single risk factor and that 52.1% were shown to have 2 or more. In there assessment of non-modifiable risk factors among the trial subjects, it was revealed that 49.9% had none, 42.4% had a single risk factor, and 7.6% maintained 2 or more.

Age-based stratification by the trial investigators indicated that nearly all individuals who were aged 65 years and older had 2 or more risk factors that might represent limitations to the utilization of oral JAKi. This was compared to 66.7% of subjects between ages 50–64 years and 41.0% of those under the age of 50.

In their stratification of participants by HS severity, it was found that 10.9% of severe HS patients were shown not to have any risk factors. This was compared to 14.4% of those reporting more moderate disease and 20.1% of individuals shown to have mild disease.

The investigators found that 15.4% of the 163 individuals included in the Danish Skin Cohort who first demonstrated a complete lack of risk factors ended up with at least 1 within the 12-month follow-up period. Overall, it was determined that only 1 in 5 of those with HS had no risk factors that could limit their utilization of oral JAKi. The number decreased to just 10% of those showing more severe HS.

“Current safety data from JAKi HS trials have not shown an increase in serious adverse events; however, these studies are limited by short follow-up periods and small sample sizes,” they wrote. “Hence, a cautious approach to oral JAKi initiation and monitoring in patients with HS is advisable.”1,3,4

References

1. Zhang, D.G., Sieborg, J., Nielsen, V.W., Nymand, L.K., Alinaghi, F., Thyssen, J.P., Egeberg, A., Maul, J.-T., Thomsen, S.F. and Holgersen, N. (2025), Prevalence of risk factors affecting the use of oral JAK inhibitors in hidradenitis suppurativa. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.20594.

2. Egeberg A, Gislason GH, Hansen PR. Risk of major adverse cardiovascular events and all-cause mortality in patients with hidradenitis Suppurativa. JAMA Dermatol. 2016; 152: 429–434.

3. Kozera E, Flora A, Frew JW. Real-world safety and clinical response of Janus kinase inhibitor upadacitinib in the treatment of hidradenitis suppurativa: a retrospective cohort study. J Am Acad Dermatol. 2022; 87: 1440–1442.

4. Kirby JS, Okun MM, Alavi A, Bechara FG, Zouboulis CC, Brown K, et al. Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study. J Am Acad Dermatol. 2024; 90: 521–529.