Upadacitinib Shows Sustained Efficacy, Safety in Moderate to Severe Atopic Dermatitis

Longer-term use of the Janus kinase (JAK) inhibitor upadacitinib showed sustained efficacy in the treatment of moderate to severe atopic dermatitis (AD) after 52 weeks, with a favorable benefit-risk profile exhibited among adult and adolescent patients. Findings were reported recently in JAMA Dermatology.

Recently approved by the FDA for the treatment of moderate to severe AD in adults and adolescents 12 years of age and older, upadacitinib’s approval was based on findings of the Measure Up 1 and Measure Up 2 double-blind, placebo-controlled, replicate phase 3 randomized clinical trials.

Previously published week-16 results from these studies indicated the JAK inhibitor was superior to placebo across assessments of disease activity, itch, skin pain, and impact of AD on quality of life.

With the evaluation of the benefit-risk profile of upadacitinib as monotherapy continuing in the ongoing blinded extension period of the Measure Up 1 and 2 studies, researchers sought to investigate its long-term (52 week) efficacy and safety in moderate to severe AD.

“Long-term oral treatment options are limited for patients with moderate to severe AD recalcitrant to topical therapy; most conventional oral immunosuppressive therapies are used off-label, have limited efficacy data, and are not suitable for long-term treatment owing to their safety profiles,” said the study authors.

“There remains an unmet need for efficacious and well-tolerated oral medications that provide rapid, sustained itch relief and skin clearance and improve quality of life for patients with moderate to severe AD," they added.

For the long-term analyses, adults and adolescents with moderate to severe AD assessed at 151 and 154 centers for the Measure Up 1 and 2 studies, respectively, were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. Cutoffs for the analyses were December 21, 2020 (Measure Up 1) and January 15, 2021 (Measure Up 2).

“At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment,” explained the study authors. “Placebo-treated patients were re-randomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner.”

A total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]) were included in the Measure Up 1 and 2 studies. Safety and efficacy was measured via 75% improvement in the Eczema Area and Severity Index (EASI) and a Validated Investigator Global Assessment for AD (VIGA-AD) score of clear (0) or almost clear (1) with 2 or greater grades of improvement.

In the findings, efficacy previously reported at week 16 was shown to be maintained through week 52 for patients in the Measure Up 1 and 2 studies who were given the 15-mg and 30mg doses of upadacitinib:

• For Measure Up 1 and Measure Up 2, respectively, EASI-75 achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose
• For Measure Up 1 and Measure Up 2, respectively, VIGA-AD score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%)
  

Adverse events leading to treatment discontinuation were low overall, but were indicated to be slightly higher for patients given the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals.

In discussing study limitations, researchers noted that these studies will continue to follow patients through 260 weeks, at which point longer-term data will be valuable for evaluating the efficacy and safety of upadacitinib for the chronic disease.

“Because of the predominance of White patients in the study populations, additional studies in underrepresented populations may be needed," authors conclued.

Reference

Simpson EL, Papp KA, Blauvelt A, 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. Published March 9, 2022. doi:10.1001/jamadermatol.2022.0029