Ruxolitinib/ruxolitinib cream has long-term safety in children, adults with AD and vitiligo

Published data from 7 Phase 3 clinical trials suggest that Ruxolitinib has a low risk of adverse events in children and adults with atopic dermatitis and non-segmental vitiligo. The team studied the long-term safety of ruxolitinib (JAK1/JAK2 inhibitor) cream in children and adults with atopic dermatitis (AD) and non-segmental vitiligo. Ruxolitinib cream is approved in the United States and Canada to treat two conditions in patients ≥12 years of age. The researchers found that although JAK inhibitors have category warnings for serious infection, thromboembolic events, MAC, and mortality, the trial showed that these adverse events were uncommon, even in patients as young as 2 years old.

The researchers calculated exposure-adjusted incidence rates (EAIR) using data from 4 phase 3 studies of mild-to-moderate atopic dermatitis and 3 phase 3 studies of nonsegmental vitiligo. EAIR is the number of patients with events per 100 PY of exposure. In the atopic dermatitis trial, patients self-assessed the recurrence of lesions between visits. If lesions clear, treatment is stopped after 3 days; if new lesions appear, patients contact the team for guidance.

All52-week atopic dermatitis trials enrolled patients with an IGA score of 2 or 3 and a BSA of 3-20% (excluding scalp). TRuE-AD3 included participants aged 2-11 years with atopic dermatitis for ≥3 months, TRuE AD½ included participants aged 12 years and older with atopic dermatitis for ≥2 years, and NCT05456529 included participants aged 12-17 years with atopic epidermatitis for ≥2 years. In TRuE-AD3 and TRuE AD½ and NCT05456529, 159 and 601 patients, respectively, received ruxolitinib 0.75% cream, and 154 and 701 patients received ruxolitinib 1.5% cream, respectively.

For the 104-week non-segmented vitiligo trial, participants aged ≥12 years had ≤10% total BSA, ≥0.5 facial BSA (F-VASI score, ≥0.5), and ≥3% non-facial BSA (T-VASI score, ≥3). In children aged 2-11 years with atopic dermatitis or vitiligo, the EAIR for serious infections, NMSC, other malignancies (excluding MACE) and thromboembolic events was low regardless of the intensity used. No deaths occurred.

Rates of serious infection (patients/100 PY) in the 2- to 11-year age group were 0 (95% confidence interval [CI], 0-3.29) and 0.89 (95% CI, 0.02-4.94), respectively, for AD treated with 0.75% and 1.5% cream. For AD patients aged ≥12 years, the incidence rates for 0.75% and 1.5% cream were 1.13 (95% CI, 0.37-2.67) and 0.92 (95% CI, 0.30-2.14), respectively. The rate of severe infection in patients with non-segmental vitiligo using the 1.5% cream was 0.46 (95% CI, 0.13-1.18). Across all trials, four patients developed pneumonia.

The researchers also found that the incidence of NMSC was low: 0 in AD patients aged 2-11 years; 0.75% and 1.5% creams had efficacy of 0.68 (95% CI, 0.14-1.98) and 0.37 (95% CI, 0.04-1.32), respectively, for ≥12 years. Patients with vitiligo also had a lower incidence of NMSC (0.12; 95% 0-0.64). Across the total patient population, there were 3 cases of cutaneous basal carcinoma and 4 cases of cutaneous squamous cell carcinoma.

MACE is rare, with no cases in AD patients aged 2-11 years or vitiligo in patients ≥12 years old. Only 2 AD patients aged ≥2 years suffered cerebrovascular accidents. No thromboembolic events occurred in AD patients aged 2 to 11 years. The other groups had lower incidence rates, with 2 cerebrovascular accidents and 2 pulmonary embolisms reported. Adverse events were considered unrelated to treatment and generally resolved without interruption or discontinuation of ruxolitinib. Plasma concentrations remain low, below 281 nM, the threshold associated with JAK-mediated myelosuppression.

The researchers concluded: The low risk of experiencing these adverse events and the low likelihood that they were caused by ruxolitinib cream are consistent with a local route of administration that minimizes systemicJAK inhibition.

Reference materials:https://www.dermatologytimes.com/view/rad-2025-poster-highlights-ruxolitinib-cream-safety-in-combination-ad-regimens