Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis (the ADAPT Randomized Clinical Trial)

Currently, systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. The use of anti-IgE medication (omalizumab) has been employed for multiple forms of atopic diseases such as severe asthma and in conjunction with oral immunotherapy during trials to treat food allergy. However, no large randomized studies in childhood atopic dermatitis have been published. The objective of this study was to determine the effectiveness of omalizumab in treating severe atopic dermatitis in children.

Eligible participants were children and adolescents aged 4 to 19 years of age who had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum topical or systemic therapy and were living in the London, UK area.

The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a single-center, double-blind, parallel-group, placebo-controlled randomized clinical trial that compared anti-IgE medication (omalizumab) with placebo to treat severe eczema in children with atopy. Before randomization, there were washout periods for other treatments that had been stopped or stabilization periods for therapies that would continue during the course of the intervention.

Each participant received 24 weeks of treatment (omalizumab, administered subcutaneously, dose based on weight and IgE levels) or placebo, which was comparable to the omalizumab in appearance, with matching excipients. Skin prick tests (SPTs) to a panel of allergens were performed at baseline and at week 24. The primary outcome was assessed by comparing SCORAD evaluations at baseline, 24, and 48 weeks. Surveys evaluating quality of life and assessments of potent topical steroids were also obtained.

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). The baseline characteristics of patients in the omalizumab and placebo groups were well matched. 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 = 0.01). 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.

Potent topical steroid use was lower in the treatment group (109 [34–164] days vs (IQR) of 161 (82–171) days in the placebo group). 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) at week 24. The omalizumab group showed a statistically significant 44% decrease in positive SPT number from baseline to week 24 compared with the placebo group (adjusted incidence rate ratio, 0.56; 95% CI, 0.40 to 0.78). There were no differences in infection rates in the two groups.

The use of omalizumab for children with severe refractory atopic dermatitis led to improvements in SCORAD assessments, increased quality of life, and provided a non-steroid treatment option.

This study reported high adherence and follow-up rates, with positive primary outcome findings through various sensitivity analyses. These findings were supported by the secondary outcomes of decreased use of potent steroids, decreased SPT, and improved quality of life. However, the sample size was small; thus, some of the uncommon secondary outcomes lacked precision. Furthermore, the SCORAD improvement of 6.9 is below the minimum clinically important difference of 8.5. While omalizumab may serve as an adjunctive therapy in severe refractory atopic dermatitis, the mild improvements reported in this study need to be balanced by the known side effects, cost, and burden of the therapy administration.

This was not an industry sponsored study, as it was funded by the NIHR EME Program and Guy’s and St Thomas’ Charity and the NHS Foundation Trust. It should be noted however, that Novartis supplied the omalizumab and placebo used in the study and the senior author also reports getting personal fees from Novartis outside of this study.