⚡Upadacitinib advances in vitiligo

Good morning — it’s Saturday, November 8, and we’re covering pivotal Phase 3 results for upadacitinib in vitiligo, late-breaking data on ruxolitinib cream in moderate atopic dermatitis, and more.

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AbbVie’s upadacitinib (Rinvoq) met all primary and key secondary endpoints in the pivotal Viti-Up Phase 3 program for non-segmental vitiligo but underperformed relative to Phase 2 results.

Investigators randomized 614 adults and adolescents across two replicate trials to upadacitinib 15 mg once daily or placebo.

At Week 48, 19–22% of patients achieved ≥50% total-body repigmentation (T-VASI 50) compared with 6% on placebo. For facial areas, 23–25% reached ≥75% repigmentation (F-VASI 75) versus 6–7% on placebo.

However, results fell short of AbbVie’s earlier Phase 2 study, where a lower 11 mg dose produced 40% T-VASI 50 and 63% F-VASI 75 responses at Week 52. The difference between the Phase 2 and Phase 3 results may reflect variations in trial design, sample size, or patient population.

Safety was consistent with prior indications. Serious adverse events occurred in 2–4% of patients, and no major cardiovascular or thromboembolic events were reported.

Upadacitinib could become the first FDA-approved systemic treatment for vitiligo. It would complement topical ruxolitinib (Opzelura), which is approved for disease involving less than 10% of the body surface area.

These results follow positive outcomes announced earlier this year from two Phase 3 trials of upadacitinib in alopecia areata, reinforcing AbbVie’s expanding immunology franchise. The oral JAK1 inhibitor generated $2.2 billion in Q3 2025, a 35% year-over-year increase.

> Ruxolitinib cream delivers rapid itch relief and strong efficacy in moderate atopic dermatitis: Incyte announced positive Phase 3b results from the TRuE-AD4 trial, presented at the 15th Georg Rajka International Symposium on Atopic Dermatitis (ISAD 2025). Ruxolitinib cream 1.5% (Opzelura), a topical JAK1/2 inhibitor, was evaluated in 241 adults with moderate atopic dermatitis (IGA 3; 10–20% BSA). All had an inadequate response or intolerance to topical corticosteroids or calcineurin inhibitors. At Week 8, 70% achieved EASI 75 (≥75% improvement in eczema severity) versus 19% with vehicle (P < 0.0001). Clinically meaningful itch relief, defined as a ≥4-point reduction on the 0–10 NRS, was statistically significant by Day 2 (30% vs 14%; P = 0.007). The cream was well tolerated. Investigators concluded that ruxolitinib cream may be an effective topical option to delay or prevent progression to systemic therapy in moderate atopic dermatitis. However, the study’s 8-week duration is a limitation. A 16-week extension phase with as-needed dosing is ongoing to assess maintenance of efficacy and tolerability.

> Roflumilast foam maintains long-term clearance and safety in seborrheic dermatitis: Roflumilast foam 0.3% (Zoryve) demonstrated durable efficacy and safety through one year in moderate-to-severe seborrheic dermatitis, according to a Phase 2 open-label extension study published in the AJCD. Overall, 400 patients aged ≥12 years applied the foam once daily to all affected areas. Of these, 338 completed 24 weeks, and 62 were enrolled for 52 weeks. The proportion of patients achieving clear or almost clear skin (IGA 0/1) was 76% (260/342) at Week 24 and 80% (37/46) at Week 52. Among patients who achieved full clearance (IGA 0) and stopped treatment (35% of the cohort), the median time to relapse was 23 weeks. Before-and-after photos are available in the supplementary materials. Roflumilast was well tolerated, with more than 96% showing no irritation at each time point. No treatment-related serious adverse events were reported. Hyper- and hypopigmentation resolved in most patients. Limitations included the non-comparative design and small 52-week cohort (n = 62). Zoryve was FDA-approved in 2023 as the first topical with a new mechanism for seborrheic dermatitis in 20 years. The drug works by reducing cyclic AMP–mediated inflammatory signaling through selective PDE4 inhibition. It has become the most prescribed branded nonsteroidal topical across atopic dermatitis, psoriasis, and seborrheic dermatitis in the U.S.

> Final 9-year analysis of adjuvant nivolumab for resected stage III or IV melanoma: The final 9-year results of the CheckMate 238 trial, published in NEJM, confirmed longer recurrence-free survival with adjuvant nivolumab than with adjuvant ipilimumab in resected stage IIIB–C or IV melanoma. A total of 906 patients were randomized to receive nivolumab or ipilimumab for up to one year. After 107 months of follow-up, the median duration of recurrence-free survival was 61 months with nivolumab versus 24 months with ipilimumab (hazard ratio for recurrence or death 0.76; 95% CI 0.63–0.90). However, overall survival was similar in both groups (hazard ratio for death 0.88; 95% CI 0.69–1.11). Fewer nivolumab-treated patients needed subsequent systemic therapy (37% vs 45%), and no new late adverse events were reported. In the primary analysis, grade 3–4 adverse events were lower with nivolumab (14% vs 46%). The authors and editorialists concluded that nivolumab remains the preferred adjuvant option over ipilimumab. However, they emphasized that adjuvant treatment decisions should be personalized. Patients and clinicians must weigh the risks of immune-related toxicities against the benefit of prolonged relapse-free survival. This is particularly important since it remains uncertain whether overall survival is longer with adjuvant therapy than with metastatic treatment.

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A long-term open-label study evaluating difamilast ointment in 41 Japanese infants aged 3–24 months with atopic dermatitis found that 81% achieved EASI 75 (≥75% improvement in disease severity) at Week 52. The selective PDE-4 inhibitor was well tolerated, with no application-site or systemic safety concerns (More)

Health Canada has approved Incyte’s ruxolitinib cream 1.5% (Opzelura) for mild-to-moderate atopic dermatitis in children aged 2–11 years, expanding its indication beyond adults and adolescents. It becomes the first JAK inhibitor cream approved in Canada for pediatric atopic dermatitis (More)

NICE has recommended LEO Pharma’s delgocitinib (Anzupgo) cream for adults with moderate-to-severe chronic hand eczema for whom topical corticosteroids are inadequate or inappropriate, making it the first topical treatment approved for this indication in England and Wales (More)