Phase 3 Results on Upadacitinib for Atopic Dermatitis with Jonathan Silverberg, MD, PhD

New phase 3 findings were presented at the 2024 American Academy of Dermatology (AAD) Annual Meeting. These results were from the Measure Up 1 and Measure Up 2 trials on the efficacy of upadactinib monotherapy for moderate-to-severe atopic dermatitis (AD) patients.¹

The new data highlighted minimal disease activity (MDA), for which the consensus-established criteria in AD includes a variety of outcomes noted by clinicians (ClinROs) like Eczema Area and Severity Index (EASI), Investigators’ Global Assessment (IGA), SCORing AD, and body surface area.

Other targets include patient-reported outcomes (PROs) such as Pain Numerical Rating Scale (NRS), Worst Pruritus NRS, Sleep NRS, Hospital Anxiety and Depression Scale, Patient-Oriented Eczema Measure, and Dermatology Life Quality Index (DLQI). For thresholds, investigators use EASI 90 and Pruritus NRS 0/1.

“In this study, we looked at 2 different doses of upadacitinib, with a 50 milligram dose and we also had a 30 milligram dose,” Jonathan Silverberg, MD, PhD, MPH, said during an interview with HCPLive. “And then (we were) looking at efficacy readouts, primary readouts were at week 16, but efficacy readouts to 52 weeks and beyond.”

Silverberg and colleagues’ results indicated that at Week 16, there were a substantially higher percentage of patients treated with the drug at 15 mg or 30 mg achieved at least one ClinRO target as opposed to those given the placebo (53.3% and 65.8% versus 10.0%, respectively). There were also a greater proportion of patients treated with 15 mg or 30 mg who reported 1 PRO target as opposed to the placebo (56.4% and 69.7% versus 16.6%, respectively).

“Overall, upadacitinib demonstrated very good efficacy and good maintenance of response with respect to achieving the minimal disease activity thresholds for both the signs of the disease as well as the symptoms,” Silverberg explained. “EASI scores and IGA Clear and NRS itch responses, et cetera. We see even higher proportions of patients achieving these MDA criteria for the 30 milligram dose compared to the 15 milligram dose.”

Additionally, the combination of patients reporting at least a single ClinRO and at least a single PRO target was also found by the research team to have been higher with the 15 mg and 30 mg treatment arms versus placebo (42.5% and 55.9% versus 6.4%, respectively). All of the p-values at the 16-week mark were noted as being less than .001.

The team’s reported MDA achievement statistics were also sustained through to the 52-week mark for those given 15 mg and 30 mg. They added that 54.2% and 59.4%, respectively, met at least a single ClinRO target and 56.0% and 68.6%, respectively, met at a single PRO target. Overall, Silverberg and his team showed that the drug demonstrated led to both achievement and maintenance of patients’ MDA, with both ClinRO and PRO optimal targets being met.

“Any way you look at it is very clear that upadacitinib is really demonstrating robust efficacy with respect to achieving this kind of deeper level of control for patients,” Silverberg said. “I think this is highly clinically relevant, because for most patients, what do they want? They want to be better. What does ‘better’ mean? Better means not only having some modest improvement on lesions or modest improvement on itch, but they want to have clear skin and they want to be itch-free. And in an ideal world, if we can do that safely, that's our goal, too. So this really, these data change the narrative a little bit.”

The US Food and Drug Administration (FDA) had approved upadacitinib in 2022 for the treatment of moderate to severe AD among adults and children 12 years and older that had been unresponsive to prior therapies.² The Measure Up 1 and 2 findings contribute to an overall understanding of the drug and its efficacy among such patients.

The quotes contained in this summary were edited for the purposes of clarity.

References

1. ^{Silverberg JI, Gooderham M, Katoh N, et al. Treatment With Upadacitinib Increases the Achievement of Minimal Disease Activity Among Patients With Moderate-to-Severe Atopic Dermatitis: Results From Phase 3 Studies (Measure Up 1 and Measure Up 2). Abstract 327. Br J Dermatol. 2023;188:ii 16-1.}
2. ^{Butera A. FDA Approves Upadacitinib for Patients 12 Years and Older with Moderate to Severe Atopic Dermatitis. HCPLive. January 14, 2022. https://www.hcplive.com/view/fda-upadacitinib-children-atopic-dermatitis. Date accessed: March 8, 2024.}