Dupilumab improves outcomes, serum biomarkers in children with atopic dermatitis
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Children with atopic dermatitis who received dupilumab experienced improvements in disease severity and decreases in severity-associated serum biomarkers, according to a study published in Pediatric Allergy and Immunology.
Treatment also had a favorable safety profile and was well tolerated by the patients through the 28-week study, Esmé Kamphuis, MD, of the department of dermatology at University Medical Center Groningen in the Netherlands, and colleagues wrote.
Study design
The study involved 16 children aged 6 to 12 years and 45 adolescents aged 12 to 18 years (overall: 49.2% male; mean age, 14 years; standard deviation [SD], 3.2) with moderate to severe AD. Also, 68.9% of the patients had two or more atopic comorbidities.
These patients visited the outpatient clinic at baseline and then after 4, 16 and 28 weeks of subcutaneous treatment with dupilumab (Dupixent, Sanofi Genzyme/Regeneron) between March 2020 and July 2022.
Adolescents who weighed less than 60 kg received a loading dose of 400 mg of dupilumab followed by 200 mg every 2 weeks. Those who weighed 60 kg or more received a loading dose of 600 mg followed by 300 mg every 2 weeks.
Children who weighed between 15 kg and 60 kg received a 300 mg loading dose, followed by another 300 mg dose 2 weeks later and then 300 mg every 4 weeks.
Treatment improvement
Overall, mean Eczema Area and Severity Index (EASI) scores fell from 20.2 (SD, 10.8) to 6.4 (SD, 7.3; P < .001). Also, 75.4% of the patients achieved a 50% or better improvement in their EASI score, 49.2% achieved an improvement of 75% or better and 24.6% saw their scores improve by 90% or better.
Additionally, 36.1% of the patients were classified as clear/almost clear on the Investigator Global Assessment 6-point scale.
Mean Numeric Rating Scale (NRS) pruritis scores improved from 6.4 (SD, 2.4) to 3.5 (SD, 2.1) and Patient-Oriented Eczema Measure (POEM) scores improved from 19.5 (SD, 7) to 9.6 (SD, 5.1; P < .001 for both).
Further, 45.3% of the patients saw their NRS pruritis scores improve by four points or more, with 77.4% of the patients seeing the same improvement in their NRS pain score and 84.7% of the patients experiencing the same improvement in their POEM score.
The researchers also found that 86.9% of patients achieved at least one absolute cutoff score indicating controlled disease after 28 weeks of treatment.
Additional indicators of successful outcomes included a 50.8% decrease in the number of patients with sleep deprivation between baseline and week 28 (OR = 0.1; P < .001) and a lack of any significant difference between weeks 16 and 28 for all outcome measures.
All 20 patients who were on oral immunosuppressive therapy were able to discontinue this treatment by week 16, 15 of whom did so by week 4.
Serum biomarker changes
When the researchers analyzed 19 biomarkers associated with severity among 17 patients, they found significant reductions in soluble IL-2-receptor alpha, periostin, thymus- and activation-regulated chemokine (TARC) and pulmonary and activation-regulated chemokine (PARC) between baseline and week 4. TARC and PARC continued to significantly decrease through week 16.
There was a significant increase in IL-4 from baseline to week 4 (median, 0.3 pg/ml vs. 1.73 pg/ml; P < .01) and a slight decrease through week 16 (median, 0.83).
There also was a significant decrease in eosinophil attraction marker eotaxin-3 from baseline to week 4 (median, 5.16 vs. 0.46; P < .05) with further stabilization at week 16. By week 16, median levels of blood eosinophils had risen from 0.64 × 109/L (interquartile range [IQR], 0.38-1.09) to 0.83 × 109/L (IQR, 0.36-1.43) as well.
Safety findings
According to the researchers, the study’s safety profile was in line with previous studies. Overall, 44.3% of patients experienced at least one side effect, most commonly conjunctivitis (16.4%) and headache (6.6%). Five patients discontinued treatment at week 28, including two due to a fear of needles, two due to a side effect (conjunctivitis and conjunctivitis/limbitis) and one due to ineffectiveness.
Based on these findings, the researchers concluded that disease severity, disease-associated symptoms and severity-associated serum biomarkers all improved safely with dupilumab among children with AD through 28 weeks.
Perspective
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Overall, the results from this study are likely to be in line with the experience that most dermatologists have had with dupilumab, which is that it is a very safe and effective treatment for most pediatric patients.
Given that dupilumab has been approved for adults for several years, with pediatric indications following more recently, the results of this study are unsurprising. However, it is crucial to have reliable, comprehensive real-world data to augment clinical trial results so that treatments can be rooted in evidence.
Based on these findings, doctors can have additional confidence that dupilumab is a very safe and effect treatment for children with AD.
Next steps in this research may include evaluation for factors associated with response (or lack of response) to treatment and with the development of side effects, so that there can be continued progress toward a goal of precision medicine approaches to treating patients with the right medication.
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