QUARTZ3 data make a case for using ivarmacitinib in atopic dermatitis

Treatment with the oral highly selective JAK1 inhibitor ivarmacitinib appears to help reduce disease activity in patients with moderate-to-severe atopic dermatitis (AD), with up to 42 percent of them having complete or near-complete clearance of involved skin areas, according to the results of the pivotal phase III QUARTZ3 trial presented at AAD 2023.

“At week 16, the proportion of patients achieving Investigator's Global Assessment (IGA) scale of 0 or 1 in the ivarmacitinib 8 mg and 4 mg groups was statistically significantly higher than that in the placebo group,” reported lead researcher Dr Yan Zhao of the Department of Dermatology, Peking University People’s Hospital in Beijing, China.

The same was true for the proportion of patients achieving a 75-percent reduction from baseline in the Eczema Area and Severity Index (EASI-75), Zhao added.

The week-16 IGA response rates were 42.0 percent with 8 mg ivarmacitinib and 36.3 percent with the 4-mg dose vs 9.0 percent with placebo (p<0.001 for both comparisons). The corresponding week-16 EASI-75 response rates were 66.1 percent and 54.0 percent vs 21.6 percent (p<0.001 for both comparisons). [AAD 2023, abstract 45845]

Another notable finding, Zhao said, is that ivarmacitinib rapidly addressed pruritus symptoms. Significantly more patients who received ivarmacitinib vs placebo achieved at least a 4-point improvement in the Worst Itch Numeric Rating Scale (WI-NRS) at week 16 (40.2 percent with the 8-mg dose and 37.2 percent with the 4-mg dose vs 12.6 percent; p<0.001 for both).

Zhao pointed out that significant IGA and EASI75 responses with ivarmacitinib, the study’s coprimary endpoints, were already evident at 4 weeks after treatment and that the 8-mg dose showed numerically greater efficacy than the 4-mg dose across all endpoints.

As for safety, “both ivarmacitinib doses were well tolerated with no increase in the incidence of serious adverse events (AEs) and AEs leading to [treatment] discontinuation compared with placebo. No major adverse cardiovascular events, thromboembolism, malignancies, or deaths were reported,” Zhao said.

Eight serious AEs occurred overall (two with 8-mg ivarmacitinib, three with the 4-mg dose, and three with placebo). These included serious infections such as varicella, sepsis, and COVID-19 pneumonia. Zhao asserted that these events were consistent with ivarmacitinib’s medication class.

QUARTZ3 included 336 patients with moderate-to-severe AD who were between 12–75 years of age. They were randomly assigned to receive monotherapy with once-daily oral ivarmacitinib at 8 mg (n=112) or 4 mg (n=113) or to placebo (n=111) for 16 weeks, followed by an extra 44-week active drug extension treatment.

JAK signaling plays an important role in the pathogenesis of AD, and ivarmacitinib’s selectivity for JAK1 is about 10-fold greater than JAK2 and 77-fold greater than JAK3, according to Zhao. Ivarmacitinib is currently under clinical development for AD as well as several other diseases, such as alopecia areata, rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease.

“The totality of ivarmacitinib efficacy and safety data [in QUARTZ3] demonstrate a favourable benefit-risk profile for 8-mg and 4-mg once-daily dose in treating patients with moderate-to-severe AD,” Zhao concluded.