Oral Ivarmacitinib Shows Promise in Atopic Dermatitis

New data were recently published showing that SHR0302, better known as ivarmacitinib, is safe and effective to use in adolescent and adult patients against atopic dermatitis, the most common chronic inflammatory subtype of eczema—specifically, moderate to severe disease.

This study was published in JAMA Dermatology.¹

Atopic dermatitis, which can have a significant impact on patient quality of life, remains challenging to treat, because it is so heterogeneous in scope—triggers include allergens, hormones, even stress—and due to a lack of objective diagnostic criteria.^2,3 Current treatments, primarily topical therapies, are often insufficient for moderate to severe cases, leading to an urgent need for efficacious systemic options, such as ivarmacitinib, a selective Janus kinase 1 (JAK1) inhibitor.

In the present analysis, a multicenter, double-blind, placebo-controlled trial, the authors enrolled 336 participants aged 12 to 75 years—mean (SD) age, 31 (15.4) years; 63.4%, male patients; 85.1% reported Asian ethnicity—across China and Canada. Patients had a confirmed diagnosis of moderate to severe atopic dermatitis, characterized by at least 10% body surface involvement; an Eczema Area and Severity Index (EASI) score of 16 or higher; and an Investigator Global Assessment (IGA) score of at least 3. Participants had previously failed or had intolerances to topical treatments, underscoring the need for additional treatment options, such as systemic therapy. Patients were randomly assigned in a 1:1:1 ratio to receive daily oral ivarmacitinib at doses of 4 mg or 8 mg, or placebo, over 16 weeks.

The primary end points were IGA score of 0 or 1 (indicating clear or almost clear skin) with at least a 2-grade improvement and a 75% reduction in dermatitis severity (EASI-75) at week 16. Overall results demonstrated that the 2 ivarmacitinib doses had significant benefits and outperformed placebo:

• In the 4-mg group, 36.3% (95% CI, 27.5%-45.9%; P < .001) achieved the primary IGA response.
• In the 8-mg group, the response rate was even higher, at 42.0% (95% CI, 32.7%-51.7%; P < .001).
• In the placebo group, the response rate was 9.0% (95% CI, 4.4%-15.9%).

For EASI-75, 54.0% (95% CI, 4.4%-15.9%) responded in the 4-mg group and 66.1% (95% CI, 56.5%-74.8%; P < .001) responded in the 8-mg group, both significantly higher than 21.6% (95% CI, 14.4%-30.4%) from the placebo group.

Ivarmacitinib is not yet approved by the FDA, with trials currently exploring its utility in disease settings that include atopic dermatitis and rheumatoid arthritis. | Image Credit: wladimir1804-stock.adobe.com

Treatment-emergent adverse events (TEAEs) occurred at similar rates in roughly two-thirds of participants across all groups, including placebo: 69.0% in the 4-mg group, 66.1% in the 8-mg group, and 64.9% in the placebo group. Serious adverse events were rare, occurring in 2.7% of the 4-mg group, 1.8% of the 8-mg group, and 2.7% of the placebo group; none of these led to patient death. Further, no new safety signals emerged, supporting the tolerability of ivarmacitinib for this patient population. Minor laboratory abnormalities and adverse events were evenly distributed, and no clinically meaningful changes in vital signs or electrocardiograms were observed.

Adverse events of special interest were also rare, occurring in just 2 patients in the 4-mg group (1 case each of varicella and sepsis) and 1 patient in the placebo group (COVID-19–related pneumonia).

Thirteen patients discontinued treatment because of TEAEs—3 patients in the 4-mg group, 4 patients in the 8-mg group, and 6 in the placebo group—which comprised the following:

• Placebo group: 2 cases of worsening atopic dermatitis and 1 case each of impetigo, psoriasis, lymphadenopathy, and liver injury
• 4-mg group: 1 case each of sepsis, varicella, and proteinuria
• 8-mg group: 2 cases of depression and 1 case each of anxiety, suicidal behavior, oral herpes, worsening atopic dermatitis, and headache

“The JAK family, including JAK1, JAK2, JAK3, and TYK2, regulates the JAK/STAT pathway, which is central to inflammation in AD. Key cytokines and thymic stromal lymphopoietin produce AD-related itching and inflammation primarily through JAK1-mediated signaling,” the authors wrote. “Consequently, targeting JAK1 pathways has become a promising strategy for moderate to severe AD.”

The study investigators noted that their findings position ivarmacitinib as a promising systemic therapy for patients with moderate to severe atopic dermatitis, especially those unresponsive to available topical treatments. Working in the JAK1 inhibitor’s favor are its oral administration and rapid onset of action, and its comparability with abrocitinib and upadacitinib—both of which are approved to treat atopic dermatitis in pediatric and adult patients.^4,5

Although the short-term results are compelling, longer-term data are needed to confirm ivarmacitinib’s ability to remain effective and safe over extended treatment periods. Further research should explore the safety profile in diverse populations and assess the drug's performance in real-world settings.

References

1. Zhao Y, Gooderham M, Yang B, et al. Ivarmacitinib for moderate to severe atopic dermatitis in adults and adolescents a phase 3 randomized clinical trial. JAMA Dermatol. 2025:e250982. doi:10.1001/jamadermatol.2025.0982

2. Atopic dermatitis. Cleveland Clinic. Updated March 4, 2025. Accessed June 6, 2025. https://my.clevelandclinic.org/health/diseases/24299-atopic-dermatitis

3. Feldman SR, Cox LS, Strowd LC, et al. The challenge of managing atopic dermatitis in the United States. Am Health Drug Benefits. 2019;12(2):83-93.

4. Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate to severe atopic dermatitis (measure up 1 and measure up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397(10290):2151-2168. doi:10.1016/S0140-6736(21)00588-2

5. Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate to severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020;396(10246):255-266. doi:10.1016/S0140-6736(20)30732-7