Baseline Serum LDH Levels Predict Dupilumab Efficacy in Atopic Dermatitis

Credit: Alexander Grey/Unsplash

New research suggests that the effectiveness of dupilumab therapy in achieving clinical outcomes may be predicted by baseline biomarkers and clinical background factors among patients with atopic dermatitis (AD).¹

After performing logistic regression analysis, investigators found background factors, including the duration of severe AD, comorbidity of food allergy, and male sex, as well as baseline serum lactate dehydrogenase (LDL) levels were negatively linked to the achievement of improved clinical outcomes.

“These factors may be useful indicators when selecting dupilumab for systemic treatment for AD,” wrote the investigative team, led by Makiko Kido-Nakahara, MD, department of dermatology, Graduate School of Medical Sciences, Kyushu University. “Further studies are needed to reveal the significance of these biomarkers in the pathogenesis of AD and their relevance to treatment with dupilumab.”

A complex relationship between skin barrier dysfunction, skin inflammation, and severe pruritis categorizes the development and progression of AD.² The disease is not defined by a single phenotype—rather, its highly heterogeneous presentation is influenced by multiple genetic and environmental factors.³

Novel therapeutic agents, including dupilumab, an anti–IL-4Rα antibody, have become available for AD treatment in recent years, but individual prediction of the ideal agent has remained complicated.⁴

In this analysis, Kido-Nakahara and colleagues evaluated the link between baseline biomarkers and patient background with the achievement of clinical outcomes after dupilumab therapy for AD.¹ The multi-center, prospective, observational study obtained samples from 19 medical facilities in Japan between October 2019 and March 2022.

A total of 131 participants were enrolled—these patients needed to have moderate-to-severe AD with an Eczema Area and Severity Index (EASI) score of ≥16, an Investigator’s Global Assessment (IGA) score of 3 or more, have eczema on at ≥10% of their body surface area and have chronic AD for ≥3 years before the start of the study.

The investigative team collected data on patient background factors, including age sex, body mass index (BMI), duration of severe AD, current comorbidity of allergic disease, current ocular comorbidities, and family history of allergic diseases. Objective clinical findings were evaluated using the EASI and patient-reported outcomes in the Patient-Oriented Eczema Measure (POEM) and Numerical Rating Scale for Pruritus (Pruritus-NRS).

After exclusions, the initial population of 131 was narrowed down to 110 in the efficacy analysis. Upon analysis, the data showed a lack of association between patient background factors and achievement of an EASI of 75 or 90.

When assessing the improvement of AD, Kido-Nakahara and colleagues identified a negative correlation between current food allergy comorbidity and achievement of an absolute EASI of ≤7. Another negative association was identified between the duration of severe AD and the achievement of a POEM score of ≤7.

Further analysis revealed a negative link between male sex and achievement of a POEM score ≤2 and current comorbidity of allergic conjunctivitis and achievement of a Pruritis-NRS score of ≤1.

Investigators also measured the association between serum baseline markers and the improvement of clinical outcomes. They identified no link between baseline biomarkers and achievement of an EASI of 75 or 90.

After evaluating the improvement of AD, the team found a negative association between baseline serum LDL levels and achievement of an EASI of ≤7. Meanwhile, no serum baseline biomarkers were correlated with the achievement of an EASI of ≤1 or a POEM score of ≤2.

A signal detection analysis, performed to examine which cutoff value for each biomarker was strongly association with better clinical outcomes, revealed a baseline serum LDL level ≤328 U/L could be a cutoff value for predicting the efficacy of dupilumab. Among those with an LDH level of 328 U/L, approximately 82% achieved an EASI of ≤7.

“This is the first report to present cutoff values of LDH level for predicting dupilumab efficacy for AD,” investigators wrote. “Serum LDH level is a clinically measurable laboratory parameter and is thus expected to become a practical indicator of the clinical response to dupilumab therapy.”

References

1. _{Kido-Nakahara M, Onozuka D, Izuhara K, et al. Biomarkers and patient-related factors associated with clinical outcomes in dupilumab-treated atopic dermatitis. J Allergy Clin Immunol Glob. 2024;3(4):100317. Published 2024 Jul 31. doi:10.1016/j.jacig.2024.100317}
2. _{Furue M, Chiba T, Tsuji G, et al. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017;66(3):398-403. doi:10.1016/j.alit.2016.12.002}
3. _{Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1-11. doi:10.1016/j.jaci.2018.10.032}
4. _{Nakahara T, Kido-Nakahara M, Onozuka D, et al. Efficacy of Dupilumab for Atopic Dermatitis According to Clinical Course and Clinical Findings: A Multicentre Retrospective Study. Acta Derm Venereol. 2021;101(11):adv00586. Published 2021 Nov 10. doi:10.2340/actadv.v101.369}