Upadacitinib Dosing Increases or Decreases Found Safe in AD

ORLANDO, Fla. — Dosing of the oral Janus kinase (JAK) inhibitor upadacitinib can be increased or decreased in adult patients with moderate to severe atopic dermatitis (AD) to achieve the desired response without serious safety concerns, a phase 3b/4 clinical trial has found.

“In treating moderate to severe atopic dermatitis using the 15-mg dose or the 30-mg dose, you can guide your dose adjustments based on the clinical response of reaching EASI [eczema area and severity index] 90 by week 12, and that would support achieving and maintaining EASI 90 with dose escalation or dose reduction through week 24,” Melinda Gooderham, MD, a dermatologist in Peterborough, Ontario, Canada, and an assistant professor at Queen’s University in Kingston, Ontario, Canada, said during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting, where she reported results from the treat-to-target, multicenter trial.

A total of 454 patients were randomized to either 15 mg or 30 mg upadacitinib once daily. Those in the low-dose group who did not reach the primary endpoint of EASI 90 at 12 weeks were switched to a 30-mg dose. Conversely, patients in the high-dose group who did reach the EASI 90 endpoint were switched to the 15-mg dose, Gooderham said.

Results After Dosing Switch

“In those patients who were started on upadacitinib 15 mg who did not achieve an EASI 90 after 12 weeks, half were able to achieve EASI 90 at week 24 after dose escalation,” Gooderham said. “Among the patients who did achieve EASI 90 on upadacitinib 30 mg after 12 weeks, two thirds of those patients were able to maintain that EASI 90 response at 24 weeks after dose-reduction therapy.”

Two thirds of the 15-mg group stepped up to 30-mg dosing at week 12, and 60% of the patients who started on 30-mg dosing stepped down to 15-mg treatment at week 12.

In the patients whose dose increased from 15 mg to 30 mg, 15% had a worst pruritis numeric rating scale (WR-NRS) of 0 or 1, with 10 representing worst pruritis, at 12 weeks when they switched to 30-mg dosing. At 24 weeks, 32.5% of those switched patients reached the WR-NRS of 0 or 1, Gooderham said.

The study used another metric, dermatology life quality index (DLQI), to evaluate patient-reported outcomes after dose escalation. At 12 weeks, 10% had a DLQI of 0 or 1 when switched to 30-mg upadacitinib. By week 24, 24% of them had achieved a DLQI of 0 or 1.

In the dose-reduction group, the study used EASI to evaluate outcomes after patients were switched from 30 mg to 15 mg at 12 weeks. At the switch, all of these patients had an EASI ≥ 90, Gooderham said. By week 24, 58.5% stayed at EASI ≥ 90, and 88.5% had EASI ≥ 75, she said.

In terms of patient-reported outcomes, 54% of the 30- to 15-mg group had a WP-NRS of 0 or 1 at the 12-week switch interval, but by week 24, 38% of them met that outcome. Half of those patients (51%) had a DLQI of 0 or 1 at the week 12 switchover, but by week 24, that had dropped to 35.4%.

Among the patients who did not make the switch to either lower- or higher-dose upadacitinib, all of the 15-mg patients had EASI 90 or better at week 12, decreasing to 75% at weeks 16 and 24, Gooderham said. In the 30-mg group who stayed on that dose level, 3.3% had EASI 90 at week 12, 19% at week 16 and 29% at week 24.

The study also evaluated safety findings, which Gooderham said, “were what we have expected from JAK selective inhibitors. There was nothing new.”

Three serious adverse events were reported across the treatment groups, Gooderham said, a rate of 0.75%. The most common treatment-related adverse event was herpes zoster, with rates of 2.8% in the 15- to 30-mg and 15-mg-only treatment groups, 1.5% in the 30- to 15-mg group, and 2.2% in the 30-mg-only group.

The size of this study makes it noteworthy for adjusting upadacitinib for AD, said Robert Dellavalle, MD, PhD, chair of dermatology at the University of Minnesota in Minneapolis and national dermatology executive program director of the Department of Veterans Affairs, who was asked to comment on the study.

“There isn’t much data for adjusting biologic drugs in patients for whom it’s working or not working, so that’s valuable information and should promote more medication adjustment based on the response,” Dellavalle said.

“It’s nice to know that you can decrease the medication and get a response; you decrease your chance of an adverse event.”

The study results confirm the drug’s safety, Dellavalle said. “There was not a great difference in adverse events in the low- or high-dose groups,” he said.

“It would be interesting to see a cost-benefit analysis for the dose adjustments,” Dellavalle added.

This study was funded by AbbVie. Gooderham reported financial relationships with AbbVie, Amgen, AnaptysBio, Arcutis, Aristea, Aslan Pharmaceuticals, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kinn, Leo Pharma, Medimmune, Meiji Seika Pharma, Merck, Moonlake, Nimbus, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Sun Pharma, Takeda, Tarsus, UCB, Union, and Vyntex. Dellavalle reported no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in Philadelphia.