Long-Term Upadacitinib for Atopic Dermatitis Safe Regardless of Oral Contraceptive Use

Females with moderate-to-severe atopic dermatitis who have up to 6 years of upadacitinib treatment had comparable long-term incidence rates of major adverse cardiovascular events, VTE, and malignancy to real-world populations with the skin condition, new findings suggest, regardless of oral contraceptive pill use.1

This study, titled ‘Patients with Atopic Dermatitis Using Oral Contraceptive Pills or Hormone Replacement Therapy: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer),’ was presented as late-breaking data at the 2025 Revolutionizing Atopic Dermaitits (RAD) Conference. It was authored by such individuals as Linda Stein Gold, MD, head of the Division of Dermatology at the Henry Ford Health System.

Serious health outcomes such as major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and certain types of cancer, excluding nonmelanoma skin cancer (exNMSC) had previously been linked to atopic dermatitis. A comprehensive evaluation was thus conducted by Stein Gold and coauthors, looking at up to 6 years of safety data from phase 3 clinical trials of upadacitinib in those with moderate-to-severe atopic dermatitis.

They sought to assess incidence rates of MACE, VTE, and malignancies excluding nonmelanoma skin cancers. Additionally, the investigative team also explored the potential role of baseline risk factors, such as use of oral contraceptives (OCPs) or hormone replacement therapy (HRT), in the development of such adverse events.

The team drew their pooled data from the randomized, double-blind, multicenter, placebo-controlled Measure Up 1 and 2 (NCT03569293/NCT03607422) and AD Up (NCT03568318) phase 3 studies. Ranomization of participants aged 12–75 years with moderate-to-severe disease had been done in a 1:1:1 ratio, with subjects receiving once-per-day oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo.

In the Measure Up analyses, treatment had been given as monotherapy, while in the AD Up analyses, upadacitinib was combined with topical corticosteroids for an initial 16-week period. By the 16-week mark, the trial participants initially receiving placebo were then re-randomized to the 15 mg or 30 mg doses, while upadacitinib-treated individuals would carry on with their assigned dose.

Stein Gold and coauthors measured incidence of VTE, MACE, and exNMSC malignancies as exposure-adjusted incidence rates per 100 patient-years (n/100PY). They estimated real-world background rates in a US atopic dermatitis population via retrospective claims data drawn from the Optum Clinformatics Data Mart, covering the timeframe between March 2017 - September 2024.

The reference population would include females with an atopic dermatitis diagnosis, based on ≥1 inpatient or ≥2 outpatient ICD-9 or ICD-10 claims, and it was adjusted to mirror the age and sex distribution of the upadacitinib trial cohort.

In the upadacitinib trials, analysis of 1,178 female participants took place (upadacitinib 15 mg: n = 593; upadacitinib 30 mg: n = 585). The investigators stratified women aged 15–55 years into subgroups based on oral contraceptive utilization and based on by HRT utilization among women older than 55 years.

Overall, Stein Gold et al found that long-term event rates had been low across all of the endpoints they evaluated: both VTE and MACE events had incidence rates that were shown to be under 0.1 events per 100 patient-years. They added that malignancies excluding NMSC had been observed at rates of 0.4 events per 100 patient-years or less.

Notably, the investigators found that no MACE or VTE events took place among participants using oral contraceptives or HRT, and they added that there were no exNMSC malignancies in the HRT cohort. However, it was noted that interpretation of HRT-associated findings had been limited given the small sample size.

Among subjects using oral contraceptives, the incidence rates observed in the long-term upadacitinib analyses were aligned with the rates that had been observed in the real-world US atopic dermatitis population. This would indicate that upadacitinib treatment does not elevate patients' risk of these serious adverse outcomes among those in this subgroup.

“In females with moderate-to-severe [atopic dermatitis] who received up to 6 years of UPA treatment, long-term incidence rates of MACE, VTE, and malignancy (exNMSC) were low, regardless of OCP use, and similar to those in the real-world population of patients with [atopic dermatitis],” Stein Gold et al concluded.1

References

1. Stein Gold L, Shahriari M, Guttman-Yassky E, et al. Patients with Atopic Dermatitis Using Oral Contraceptive Pills or Hormone Replacement Therapy: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer). Poster presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7, 2025; Nashville, TN.