Real-World Cohort Ties JAK Inhibitors in Alopecia Areata to Menstrual Side Effects

Menstrual alterations emerged as a newly described safety signal and the leading cause of safety-related treatment discontinuation among women treated with a Janus kinase (JAK) inhibitor for alopecia areata or atopic dermatitis, according to a single-center retrospective cohort study published in Dermatology and Therapy.¹

Trial Data Left Real-World JAK Inhibitor Safety Largely Unexamined

Abrocitinib, baricitinib, and upadacitinib are approved in the European Union for atopic dermatitis, and baricitinib and ritlecitinib are approved for alopecia areata; randomized trials of all 4 drugs have shown favorable safety profiles. In January 2023, the European Medicines Agency's safety committee nonetheless confirmed new measures for JAK inhibitors as a class, citing risks of major cardiovascular problems, blood clots, cancer, and serious infections, and calling for more real-world safety data in patients with chronic inflammatory disorders.²

Clinical trial populations are selected and closely monitored, so how these drugs behave in the more heterogeneous patients and less standardized monitoring of routine dermatology practice has remained largely unexamined.

The researchers retrospectively reviewed electronic medical records from a single dermatology center in Milan, Italy, identifying adults with alopecia areata or atopic dermatitis who were treated with abrocitinib, baricitinib, ritlecitinib, or upadacitinib for at least 4 weeks between December 2020 and June 2025.¹

The analysis included 376 patients with a mean age of 42.6 years, 60% of them female, contributing a combined 521.9 patient-years of exposure (a mean of 1.4 years each). Hypercholesterolemia, thyroid disease, and hypertension were the most common comorbidities, and most patients had a body mass index in the normal range.

Menstrual Disturbances Were the Top Safety-Related Reason for Stopping Treatment

Among the 34% of patients who were women of reproductive age, 18 cases of menstrual disturbance, including amenorrhea, abnormal bleeding, and dysmenorrhea, occurred over the study period (12.4 per 100 patient-years), most often with baricitinib (13.4 per 100 patient-years) and upadacitinib (10.67 per 100 patient-years); 2 cases occurred with abrocitinib, and none with ritlecitinib. Ten patients stopped treatment because of menstrual disturbances, making it the single leading adverse event behind a safety-related discontinuation.

Weight gain exceeding 5% of body weight was the second most common adverse event in the full cohort (8.6 per 100 patient-years) and showed a similar sex split: it occurred more than twice as often in women as in men (11.2 vs 5.3 per 100 patient-years), and severe weight gain of more than 10% of body weight was also more common among women (4.4 vs 1.3 per 100 patient-years).

“The association observed in our cohort should be considered hypothesis-generating rather than evidence of a causal relationship,” the researchers wrote.

Most Common Adverse Events Overall: Cholesterol Elevation

Mild total cholesterol elevation was the single most frequent adverse event across the cohort (18.0 per 100 patient-years), ahead of weight gain, upper respiratory tract infection (8.1 per 100 patient-years), and acne (7.3 per 100 patient-years), the fourth most common event overall.

No major adverse cardiovascular events occurred, and only 1 venous thromboembolic event was reported in a patient who also had other thrombotic risk factors. Four malignancies other than nonmelanoma skin cancer were identified, a rate the researchers said was comparable with that reported in the general population.

Overall, 135 of the 376 patients discontinued treatment (25.9 per 100 patient-years), most often because the drug lost effectiveness over time rather than for safety reasons; discontinuation rates were highest with abrocitinib (48.5 per 100 patient-years) and lowest with ritlecitinib (17.6 per 100 patient-years), though the researchers cautioned that shorter follow-up on those 2 drugs could inflate their rates.

Adverse events prompted discontinuation in 36 patients, with menstrual disturbances the single leading reason, ahead of infections such as recurrent upper respiratory infections and herpes zoster.

The study was retrospective and conducted at a single center without a control group, and laboratory monitoring was not performed on a standardized schedule, with lipid testing in particular becoming more common only later in the study period; the researchers said this could have led to underdetection of some laboratory abnormalities in earlier years. Shorter follow-up for ritlecitinib and abrocitinib may also have inflated their incidence estimates, and information on concomitant medications was not consistently available, leaving room for residual confounding.

References

1. Facheris P, Gargiulo L, Ibba L, et al. JAK inhibitor safety in atopic dermatitis and alopecia areata: a 4.5-year real-world retrospective cohort study. Dermatol Ther (Heidelb). 2026;16(9):4305-4324. doi:10.1007/s13555-026-01867-y
2. European Medicines Agency. EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. January 23, 2023. Accessed October 12, 2026. https://www.ema.europa.eu/en/news/ema-confirms-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic-inflammatory-disorders