Background:

Evidence for systemic treatments for severe childhood eczema is limited. Systemic immunosuppressants are unlicensed for use in children and are associated with unwanted side effects.

Objective:

To examine the role of anti-immunoglobulin E (IgE) [omalizumab (Xolair^®, Novartis Pharmaceuticals UK Ltd, Frimley, UK)] in children and young people with severe eczema.

Design:

A double-blind, placebo-controlled, parallel-arm randomised (1 : 1) trial.

Setting:

A single specialist centre – Guy’s and St Thomas’ NHS Foundation Trust, London.

Participants:

Atopic children and young people (aged 4–19 years) with severe eczema.

Interventions:

Treatment with omalizumab or placebo for 24 weeks.

Main outcome measures:

The primary outcome was eczema severity, measured using the objective SCORing Atopic Dermatitis (SCORAD) at 24 weeks. Secondary outcomes included validated measures of eczema severity, quality of life (QoL) and potent topical steroid use.

Results:

Sixty-two participants, with a median baseline total IgE level of 8373 kU/l, received treatment with omalizumab (n = 30) or placebo (n = 32). The unadjusted mean objective SCORAD score at week 24 was 43.1 [standard deviation (SD) 12.5] for participants in the omalizumab arm and 49.2 (SD 11.3) for participants in the placebo arm. After adjustment for baseline objective SCORAD score, age and IgE level, the mean difference between arms at 24 weeks was –6.9 [95% confidence interval (CI) –12.2 to –1.5; p = 0.013], in favour of omalizumab. The mean objective SCORAD scores improved by –12.4 and –5.1 in the omalizumab and placebo arms, respectively, by 24 weeks. Secondary outcome measure estimates were also in favour of omalizumab for eczema severity at 24 weeks: the adjusted mean treatment arm difference was –8.3 (95% CI –15.1 to –1.1; p = 0.024) for total combined objective and subjective SCORAD and –6.7 (95% CI –13.2 to –0.1; p = 0.046) for the Eczema Area and Severity Index, with less effect on the Patient-Oriented Eczema Measure (POEM; –1.1, 95% CI –4.6 to 2.4; p = 0.527). Treatment estimate precision was limited by the sample size. The QoL measures favoured omalizumab, with an improvement (reduction) in both (Children’s) Dermatology Life Quality Index [(C)DLQI] score (mean –3.5, 95% CI –6.4 to –0.5; p = 0.022) and Paediatric Allergic Disease Quality of Life Questionnaire score (mean –0.5, 95% CI –0.9 to 0.0; p = 0.050). The mean (C)DLQI score improved by 50%, from 17.0 (SD 5.6) at baseline to 8.5 (SD 5.9) at week 24, for patients treated with omalizumab. Improvements were seen despite lower potent topical steroid use in the omalizumab arm, with 48% more days of use than (109 days in the placebo arm vs. 161 days in the omalizumab arm) and twice the body surface area coverage of (15.5% in the placebo arm vs. 31.3% in the omalizumab arm) the placebo arm. There were fewer treatment failures and new systemic immunosuppression initiations in the omalizumab arm. There was no difference in the numbers of cases of infective eczema and eczema exacerbation. There was one suspected severe adverse reaction in the omalizumab arm. In each arm, six participants reported a total of seven severe adverse events that were unrelated to treatment. Non-serious respiratory and dermatological adverse event rates were higher in the placebo arm (incidence rate ratio 0.69, 95% CI 0.49 to 0.96).

Conclusions:

Omalizumab, in a highly atopic paediatric population with severe eczema, reduced eczema severity and improved QoL despite a reduction in potent steroid use and highly elevated total IgE levels. Omalizumab, with its favourable side effect profile, warrants further study as a treatment option for this difficult-to-manage population. Further studies are needed to clarify the role of omalizumab. Treatment benefit became more apparent towards 24 weeks and persisted after treatment stopped. The optimal duration of treatment needs to be determined.

Trial registration:

This trial is registered as ISRCTN15090567, EudraCT 2010-020841-29 and ClinicalTrials.gov NCT02300701.

Funding:

This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 5. See the NIHR Journals Library website for further project information. A grant from the Guy’s and St Thomas’ Charity supported the Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT). Omalizumab and the placebo were supplied by Novartis Pharmaceuticals UK Ltd.

Article history

The research reported in this issue of the journal was funded by the EME programme as project number 11/14/24. The contractual start date was in January 2014. The final report began editorial review in March 2018 and was accepted for publication in September 2018. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The EME editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.