Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis: The ADAPT Randomized Clinical Trial

Abstract

Importance: Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published.

Objective: To determine the effectiveness of omalizumab in treating severe atopic dermatitis in children.

Design, setting, and participants: The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single-center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n = 62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle.

Interventions: Subcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization.

Main outcomes and measures: Objective SCORAD index after 24 weeks of treatment.

Results: In total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n = 30) or placebo (n = 32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P = .01), significantly favoring omalizumab therapy and reflecting the results in other assessments of atopic dermatitis severity. Improved quality-of-life scores were seen in the omalizumab group, as measured by the Children's Dermatology Life Quality Index/Dermatology Life Quality Index (-3.5; 95% CI, -6.4 to -0.5) and Pediatric Allergic Disease Quality of Life Questionnaire score (-0.5; 95% CI, -0.9 to -0.0). Improvements in disease severity occurred despite lower potent topical corticosteroid use in the omalizumab group compared with the placebo group (median [interquartile range (IQR)] percentage of body surface area covered, 16% [10%-46%] vs 31% [14%-55%]; median [IQR] number of days of use, 109 [34-164] days vs 161 [82-171] days).

Conclusions and relevance: This randomized clinical trial found that omalizumab significantly reduced atopic dermatitis severity and improved quality of life in a pediatric population with atopy and severe eczema despite highly elevated total IgE levels at baseline. The result was associated with a potent topical corticosteroid sparing effect and may suggest that omalizumab is a treatment option for difficult-to-manage severe eczema in children with atopy.

Trial registration: ClinicalTrials.gov identifier: NCT02300701.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Chan reported receiving grants from the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme, grants from Guy's and St Thomas’ Charity, and active and placebo drugs from Novartis during the conduct of the study. Dr Cro reported receiving grants from the NIHR EME Programme and Guy's and St Thomas’ Charity during the conduct of the study. Dr Lack reported receiving grants from the NIHR EME Programme and Guy's and St Thomas' Charity during the conduct of the study; active and placebo drugs from Novartis, DBV Technologies, and Mighty Mission Me during the conduct of the study; and personal fees from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Participant Flow

One participant was randomized in error and found to be ineligible later; therefore, this participant was not offered any treatment and was excluded from the study and intention-to-treat analysis.

Figure 2.. Atopic Dermatitis Severity and Quality of Life in Participants During the 24-Week Treatment and 48-Week Follow-up Periods

CDLQI/DLQI indicates Children’s Dermatology Life Quality Index/Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; and SCORAD, Scoring Atopic Dermatitis.

Figure 3.. Proportion of Patients Using Potent Topical Corticosteroids During the 24-Week Treatment and 48-Week Follow-up Periods