麻豆传媒

Omalizumab (Xolair) significantly improved symptoms for children with severe atopic dermatitis and reduced their reliance on topical corticosteroids, the ADAPT trial found.

In a group of over 60 children, those randomized to subcutaneous omalizumab showed significant reductions at week 24 on the objective Scoring Atopic Dermatitis (SCORAD) index compared to those administered placebo, meeting the trial's primary endpoint (-6.9 difference, 95% CI -12.2 to -1.5), reported Susan Chan, MD, of Guy's and St. Thomas' NHS Foundation Trust in London, and colleagues.

As described in , the anti-IgE medication also led to improved quality of life versus placebo at this time point, based on the Children's Dermatology Life Quality Index (-3.5 difference, 95% CI -6.4 to -0.5) and the Pediatric Allergic Disease Quality of Life Questionnaire (-0.5 difference, 95% CI -0.9 to -0.0).

"Anti-IgE medication may be a cost-effective option in the multisystem, difficult-to-manage allergic disease that burdens many children at the severe end of the spectrum," Chan and colleagues wrote.

Omalizumab, in kids ages 6 years and older, works by binding to and neutralizing free-circulating IgE.

Atopic dermatitis is often mediated through IgE in children. In ADAPT (Atopic Dermatitis Anti-IgE Pediatric Trial), baseline IgE levels were 5.6 times higher than the range that the top dose of omalizumab is designed for. The doses of omalizumab were also higher than those used in other studies, with a maximum target level of 1,500 IU/mL.

In this trial, participants with lower baseline IgE levels responded better to treatment, "suggesting that anti-IgE medication may be more effective when the dose is high enough to neutralize free-circulating IgE," the authors noted.

It makes "logical sense" that omalizumab could be therapeutic for atopic dermatitis, but whether it is an "overtreatment" or a "life-saver" needs further study, wrote Ann Chen Wu, MD, MPH, of Harvard Medical School in Boston, in an .

At the upper bound of the doses used in this study (1,200 mg), omalizumab would cost patients $8,850 a month, Wu noted.

However, atopic dermatitis is also expensive. With the price of appointments and prescriptions, as well as indirect costs like time taken off work, the disease was estimated to .

It may be that the therapy is cost-effective for certain subgroups of individuals with severe atopic dermatitis and not for others, which remains a question for further studies, Wu noted.

"Even if the routine use of omalizumab for atopic dermatitis may not occur immediately, evaluating the efficacy of biological agents in treating atopic dermatitis will continue," Wu wrote.

For this study, 62 patients ages 4 to 19 years with atopic dermatitis -- defined as scores higher than 40 on the objective SCORAD index -- were randomized to either omalizumab or placebo for 24 weeks. The data were controlled for baseline SCORAD scores, age, and IgE levels.

Conducted in London, the cohort (mean age 10.3 years; 52% male) was composed of a majority of Asian, black, and mixed-race children; just 33% were white. There were no significant differences in any of the characteristics measured between the treatment and placebo arms. Overall, participants had a median IgE level of 8,373 IU/mL at baseline -- which is 12 times higher than the top normal range -- and a mean total SCORAD index score of 69.3.

Overall, omalizumab was associated with improved symptoms compared with placebo across a variety of measures, including:

• Eczema Area and Severity Index: -6.7 difference (95% CI -13.2 to -0.1)
• Objective plus subjective SCORAD: -8.3 difference (95% CI -15.1 to -1.1)

The number of days during the study in which participants required topical corticosteroids was 48% higher in the placebo group versus the omalizumab group (161 vs 109 days), and the percentage of body surface area corticosteroids were used on was twice as much in the placebo group (31% vs 16%), the authors reported.

Less clear, however, was how sustainable the benefit with omalizumab was. An analysis at week 48 on improvements in the objective SCORAD index showed no significant difference between the two arms (-2.8 difference, 95% CI -8.6 to 3.0).

Finally, one and five participants in the omalizumab and placebo groups, respectively, required at least two courses of rescue therapy. Also, one patient in the active arm discontinued treatment because of an anaphylaxis incident, which is notable considering the black box warning added to omalizumab in 2007 for anaphylaxis risk.

Altogether, seven serious adverse events among six patients occurred in each group. Exacerbations were similar in the omalizumab and placebo groups (17% vs 19%). Respiratory events were slightly less frequent with omalizumab (50% vs 78%), as were dermatological events (77% vs 97%).

Since participants could use corticosteroids for symptom relief across the trial period, the difference between the groups may have been minimized, which is a study limitation, the authors noted. Also, the sample size was relatively small, and some of the secondary outcomes may have lacked precision.

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