The efficacy and safety of oral upadacitinib (Rinvoq) in patients with moderate to severe atopic dermatitis observed in two phase III randomized trials was maintained out to week 52 in a blinded extension study, researchers reported.
In the ongoing Measure Up 1 and 2 trials, 82% of patients randomized to one of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI75) through 52 weeks. The results included placebo-treated patients who were randomized to the different upadacitinib doses after the 16-week primary assessment, according to Emma Guttman-Yassky, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues.
In addition, 87% to 91% of patients from the two trials who had attained EASI75 responses at 16 weeks maintained those responses at week 52, they reported in .
Achieving that level of control with an oral agent could make upadacitinib an attractive option for some patients with atopic dermatitis, the authors noted. "A lot of people don't like to inject drugs so as an oral agent, upadacitinib is appealing," Guttman-Yassky told 鶹ý.
Upadacitinib also has broader immune activity, targeting more immune pathways than dupilumab (Dupixent) does, but "we don't yet have the same kind of safety data that we have for dupilumab," she said. However, "we have had many patients at our own center who have already been treated for 2 years now [with upadacitinib], and they're great. The bottom line is we now have more options for our patients. Upadacitinib is [FDA] and it easily gets us to at least 90% clearance, so this drug might be for you if you do not get full clearance on dupilumab," she stated.
Measure Up 1 and 2 included 1,609 patients, ages 12 to 75, with moderate to severe atopic dermatitis, defined as at least 10% of body surface area affected. They were randomized to 15 mg or 30 mg of upadacitinib daily or to placebo, and assessment of the primary endpoint (EASI75) occurred after 16 weeks of treatment. At that point, patients originally allocated to the JAK inhibitor continued at the assigned dose, and placebo-treated patients were randomized to one of the upadacitinib doses for the extension phase. Initial results were published in 2021 in .
At week 52, 82% of patients in the 15-mg arm of Measure Up 1 met EASI75 response criteria as did almost 85% of those treated with the 30-mg dose. The 52-week EASI75 response rates in Measure Up 2 were 79.1% with 15 mg upadacitinib and 84% with 30 mg.
About 59% of patients on the 15-mg dose in Measure Up 1 and 62% of patients on the 30-mg dose achieved a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0/1 response, plus at least a two-grade improvement from baseline. Rates for the same dose groups in Measure Up 2 were 53% and 65%, respectively.
Similarly, two-thirds of patients on both upadacitinib doses had a least a 4-point improvement in pruritus score in Measure Up 1, as did 62% of 15-mg dose patients and 73% of those assigned to 30 mg in Measure Up 2.
The authors also noted "meaningful improvements" on patient-reported outcome assessments: Dermatology Life Quality Index; Hospital Anxiety and Depression Scale; and the Atopic Dermatitis Impact Scale (sleep, emotional state, and daily activities domains).
"Placebo-treated patients who were re-randomized at week 16 to upadacitinib achieved similar response trends through study week 52 to those who received upadacitinib from day 1, confirming the findings from the double-blind period," they added.
Loss of response between weeks 16 and 52 occurred infrequently, the authors reported, and rates of treatment discontinuation because of adverse events were low with both doses of upadacitinib.
"In this analysis of follow-up data from two randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile with sustained efficacy response through 52 weeks," they concluded, adding that patients will be followed through 260 weeks.
A limitation of the trial was the predominance of white patients so "additional studies in underrepresented populations may be needed," according to Guttman-Yassky's group.
Disclosures
The Measure Up trials are supported by AbbVie.
Guttman-Yassky disclosed support from AbbVie. Co-authors disclosed multiple relationships with industry including AbbVie.
Primary Source
JAMA Dermatology
Simpson EL, et al "Efficacy and safety of upadacitinib in patients with moderate to severe atopic dermatitis: analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials" JAMA Dermatol 2022; DOI: 10.1001/jamadermatol.2022.0029.