Sustained Efficacy Noted in Long-Term Upadacitinib Dosing in AD Patients

Eric Simpson, MD

An analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials found that longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib was associated with a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.

Primary results from these 2 phase 3 trials demonstrated efficacy and safety of the biologic through 16 weeks in patients with atopic dermatitis, but longer-term outcomes remained unknown.

Additionally, long-term oral treatments options are still limited for patients with moderate to severe atopic dermatitis who are recalcitrant to topical therapy, leaving an unmet need for efficacious and well-tolerated oral medications.

As such, investigators led by Eric Simpson, MD, Department of Dermatology at Oregon Health & Science University, Portland, reported on results of the ongoing blind extension (BE) period of the Measure Up 1 and Measure Up 2 trials.

The Methods

Measure Up 1 and Measure Up 2 were global, multi-center double-blind, placebo-controlled phase 3 trials conducted in 151 and 154 centers, respectively. Both consisted of a 35-day screening period, a 16-week double-blind treatment period, and a BE period up to 260 weeks.

Patients aged 12-75 years with moderate to severe atopic dermatitis were eligible to participate.

Patients were randomized 1:1:1 to receive a daily oral dose of upadacitinib 15 mg, upadacitinib 30 mg, or placebo, and patients initially randomized to upadacitinib 15 mg or upadacitinib 30 mg continued treatment at week 16.

Placebo-treated patients were rerandomized 1:1 at week 16 to upadacitinib 15 mg or 30 mg, and randomization was stratified by Eczema Area and Severity Index (EASI 50) response at week 16, age group, and geographic region.

Safety and efficacy, including 75% improvement in the EASI and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed.

The Findings

Between both trials a total of 1609 patients were included in the study, including 727 women (45.2%) and 882 men (54.8%).

The team observed that efficacy at week 16 was maintained through week 52, and a 75% improvement in EASI was achieved by 82% and 79.1% of all patients continuing the 15 mg dose in the Measure Up 1 and Measure Up 2 trials, respectively.

Additionally, 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose also achieved a 75% improvement in EASI.

Validated Investigator Global Assessment for Atopic Dermatitis 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%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively.

Treatment discontinuation from adverse events were low in both trials, yet slightly higher for the upadacitinib 30-mg dose.

“Altogether, while longer-term treatment of moderate to severe AD with upadacitinib (both 15-mg and 30-mg doses) has a favorable benefit-risk profile, upadacitinib 30 mg may provide added benefit for patients with higher disease burdens that may require more rapid or more complete response to treatment,” the team wrote.

The study, "Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic DermatitisAnalysis of Follow-up Data From the Measure Up 1 and Measure Up 2 Randomized Clinical Trials," was published online in JAMA Dermatology.