Biomarker Insights Differentiate JAK1 vs IL-13 Therapy in AD

Janus kinase 1 (JAK1) inhibitors showed potential superior efficacy vs anti–IL-13 antibodies among 75 patients receiving treatment for moderate to severe atopic dermatitis (AD), with authors noting their increased antipruritic effects as soon as 3 months.¹

However, thymus and activation-regulated chemokine (TARC) levels also indicated potential benefits of IL-13 antibodies, they noted, which led them to conclude that longer-term analyses are need in these patients. Their findings were published in Frontiers in Immunology.

Much uncertainty remains on the best predictive biomarkers for AD treatment response, with several promising new agents introduced in the past few years, both internationally and in the US.^2-4 To evaluate their effectiveness per administered treatment, the study investigators conducted a retrospective analysis among patients receiving care at Fukuoka University Hospital in Japan, using baseline and 3-month measures of eosinophil count and TARC to determine response. Thirty-seven patients were in the JAK1 inhibitor cohort and 38 were in the IL-13 antibody cohort. Most patients in each group were male (68.42%, JAK1; 57.89%, IL-13; P = .476), predisposed to atopic disease (97.30% and 86.84%, respectively; P = .1997), and biologic naive (70.27% and 52.63%).

Overall, patients in the JAK1 inhibitor cohort were younger (38 years vs 57 years; P = .0054), had higher median (IQR) baseline scores on the Eczema Area and Severity Index (EASI; 26.5 [18.7-38.5] vs 18.7 [16.5-24.2]; P = .0019) and Peak Pruritus Numerical Rating Scale (PP-NRS; 7 [4.5-8.0] vs 6 [3-9]; P = .4265), and had higher baseline levels of eosinophils (455 [243.0-775.3] vs 416.4 [249.4-728.3]; P = .7667), serum immunoglobulin E (IgE; 4071 [1735.5-12,166] vs 1585 [298.75-5628.25]; P = .0271), and serum TARC (2949 [1185.5-7021.0] vs 1901 [457.5-3445.0]; P = .0142).

Also at baseline, there were no significant differences in history of systemic therapy.

Three months after treatment, the following results were seen:

• PP-NRS score: 100% of patients in the JAK1 inhibitor group vs 60% of the IL-13 antibody group demonstrated improvement (P < .0001)
• EASI score: 83.33% vs 79.98% exhibited improvement (P = .4280)
• Eosinophil count: 56.83% saw improvement vs 25.92% who worsened (P < .0001)
• Serum IgE level: 7.96% improved vs 21.48% (P = .2591)
• Serum TARC level: 37.22% improved vs 55.01% (P = .1667)
• Adverse events: 26 vs 18 reported (P = .6438)
• Final PP-NRS scores: 0 vs 2 (P = .0003

“Further prospective studies with larger cohorts and longer follow-up periods are warranted,” the study authors wrote, “to validate these findings and to establish long-term treatment algorithms.” | Image Credit: © slobodyan_78-stock.adobe.com

The authors highlighted, in particular, that multivariate logic regression analysis identified JAK1 inhibitors as independent predictors for achieving 2 important outcomes vs the IL-13 cohort:

• Achieving PP-NRS 4: OR, 9.36 (95% CI, 1.88-46.52; P = .0063); 30% vs 17% reached this milestone
• Achieving PP-NRS 0/1: OR, 34.61 (95% CI, 5.93-202.04; P < .0001); 27% vs 8% reached this milestone

Additional analyses demonstrated that baseline EASI score, TARC improvement rate, and IgE improvement rate were significant predictors of EASI-75 achievement, even though baseline IgE and TARC improvement rate “were associated factors with adverse events, although their ORs were close to 1, indicating a limited predictive effect.” Further, there were positive correlations seen between eosinophil improvement rate in the patients who received JAK1 inhibitors and overall EASI and PP-NRS improvements, and negative correlations between baseline IgE levels and patient improvement in those who received IL-13 antibodies.

Adverse event rates were similar between the groups, at 45.95% in the JAK1 inhibitor group and 39.47% in the IL-13 antibody group (P = .6438). These encompassed acne or folliculitis, viral warts, herpes zoster, ocular pruritus or conjunctivitis, fatigue, asthma exacerbation, and grade 3 eosinophilia. Severe adverse events were rare.

“Importantly, our study is the first to directly compare selective JAK1 [inhibitors] and IL-13 [antibodies], with a focus on pathway-specific biomarkers,” the study authors wrote. “This direct comparison provides novel insights into personalized therapeutic strategies for atopic dermatitis.”

They explained potential limitations on their findings, including that it was a retrospective analysis, had small sample size and a short follow-up, and residual confounding from the baseline measurements considering different prescribing patterns in clinical practice.

“Further prospective studies with larger cohorts and longer follow-up periods are warranted,” they concluded, “to validate these findings and to establish long-term treatment algorithms.”

References

1. Sato E, Obonai N, Iwata M, Ito K, Imafuku S. Comparative short-term efficacy of Janus kinase 1 inhibitors and anti-interleukin-13 antibodies in atopic dermatitis: a retrospective cohort analysis based on real-world data. Front Immunol. 2025:16:1639932. doi:10.3389/fimmu.2025.1639932
2. Kamata M, Tada Y. Optimal use of Jak inhibitors and biologics for atopic dermatitis on the basis of the current evidence. JID Innov. 2023;3(3):100195. doi:10.1016/j.xjidi.2023.100195
3. Kamata M, Sun DI, Paller AS. Deciding which patients with atopic dermatitis to prioritize for biologics and Janus kinase inhibitors. J Allergy Clin Immunol Pract. 2025;13(8):1901-1910.e1.doi:10.1016/j.jaip.2025.04.042
4. McCormick B. FDA approves roflumilast for patients 6 years and older with atopic dermatitis. AJMC^®. July 9, 2024. Accessed September 9, 2025. https://www.ajmc.com/view/fda-approves-roflumilast-for-patients-6-years-and-older-with-atopic-dermatitis