Upadacitinib improved symptoms, QoL in moderate-to-severe AD

Upadacitinib monotherapy improved symptoms and quality of life (QoL) in adolescents and adults with moderate-to-severe atopic dermatitis (AD), according to the phase III Measure Up 1 and 2 studies presented at EADV 2020.

“Both studies met the co-primary and all secondary endpoints, demonstrating superiority of upadacitinib 15 mg and 30 mg vs placebo,” said Professor Emma Guttman-Yassky from the Icahn School of Medicine, Mount Sinai Medical Center, New York, US, and co-authors.

Participants in the two multicentre, double-blind studies were adolescents (aged 12–17 years with body weight ≥40 kg) and adults (aged 18–75 years) with moderate-to-severe AD*. The 847 and 836 patients in Measure Up 1 and Measure Up 2, respectively, were randomized 1:1:1 to receive once-daily doses of upadacitinib 15 mg, 30 mg, or placebo for 16 weeks. Adolescents made up 14.6 and 12.4 percent of the Measure Up 1 and Measure Up 2 cohorts, respectively. Baseline mean EASI scores and proportion of patients with severe vIGA-AD were well balanced across groups.

At week 16, more patients in both upadacitinib groups achieved EASI 75** compared with placebo (Measure Up 1: 69.6 percent [15 mg] and 79.7 percent [30 mg] vs 16.3 percent [placebo]; Measure Up 2: 60.1 percent and 72.9 percent vs 13.3 percent; p<0.001 for  each upadacitinib dose vs placebo). [EADV 2020, Presentation ID D3T03.4B – 3154]

More patients on upadacitinib than placebo also achieved vIGA-AD of 0 (clear) or 1 (almost clear) with ≥2 grades reduction from baseline (vIGA-AD 0/1; Measure Up 1: 48.1 percent [15 mg] and 62.0 percent [30 mg] vs 8.4 percent [placebo]; Measure Up 2: 38.8 percent and 52.0 percent vs 4.7 percent; p<0.001 for upadacitinib vs placebo).

At week 16, achievement of EASI 90** was also more frequent among patients on upadacitinib than placebo (Measure Up 1: 53.1 percent [15 mg] and 65.8 percent [30 mg] vs 8.1 percent [placebo]; Measure Up 2: 42.4 percent and 58.5 percent vs 5.4 percent; p<0.001 for all).

More patients on upadacitinib than placebo achieved a ≥4 percent improvement in Worst Pruritus NRS score at 16 weeks (Measure Up 1: 52.2 percent [15 mg] and 60.0 percent [30 mg] vs 11.8 percent [placebo]; Measure Up 2: 41.9 percent and 59.6 percent vs 9.1 percent; p<0.001 for all). This improvement was evident as early as week 4 (Measure Up 1: 51.5 percent and 66.8 percent vs 4.4 percent; Measure Up 2: 48.9 percent and 60.7 percent vs 3.6 percent; p<0.001 for all).

QoL at 16 weeks was also significantly improved with upadacitinib vs placebo. For example, among patients aged ≥16 years with baseline Dermatology Life Quality Index (DLQI) score >1, DLQI 0/1 was achieved by more upadacitinib than placebo recipients in both trials (Measure Up 1: 30.3 percent [15 mg] and 41.5 percent [30 mg] vs 4.4 percent [placebo]; Measure Up 2: 23.8 percent and 37.9 percent vs 4.7 percent; p<0.001 for all).

The response rates of upadacitinib pertaining to both EASI 75 and vIGA-AD 0/1 and secondary endpoints were numerically higher with the 30 mg than the 15 mg dose.

Acceptable safety profile

Serious adverse event (AE) rate was low with both upadacitinib doses (15 mg: 2.1 and 1.8 percent in Measure Up 1 and 2, respectively; 30 mg: 2.8 and 2.5 percent) vs placebo (2.8 and 2.9 percent). AEs led to discontinuation in 4.3 percent of placebo recipients in both studies, 1.4 and 4.0 percent of upadacitinib 15 mg recipients in Measure Up 1 and 2, respectively, and 3.9 and 2.5 percent of upadacitinib 30 mg recipients in Measure Up 1 and 2, respectively. There were no deaths.

The most frequent treatment-emergent AEs (≥5 percent in any group) were acne, upper respiratory tract infection, nasopharyngitis, headache, elevated blood creatine phosphokinase (Measure Up 1), and AD.

Serious infections were rare, with comparable rates across treatments. There were no reports of active tuberculosis, adjudicated gastrointestinal perforations or major adverse cardiovascular events, or renal dysfunction. There were some herpes zoster and eczema herpeticum cases, but none led to discontinuations. There were also some cases of cytopenias, with two related discontinuations.

“No new safety signals were observed compared with the known safety profile of upadacitinib, except for higher rates of acne,” said Guttman-Yassky and co-authors. Most cases of acne were mild, with few moderate, and just one severe event, with two moderate acne-related discontinuations in upadacitinib recipients.

Additional systemic treatment options are needed for patients with moderate-to-severe AD, said Guttman-Yassky.

In these studies, improvements were seen in all aspects of AD, from skin disease activity to itch and patient-reported QoL, she continued, noting the speed of response, with improvements in itch reported as early as the day after the first dose.

“[B]oth upadacitinib monotherapy doses demonstrated high degrees of efficacy and improved QoL in adolescents and adults with moderate-to-severe AD,” the authors said.