Adverse Events, Inadequate Responses to Dupilumab in Pediatric Patients with AD

Though well-tolerated and highly efficacious, the biologic was linked several adverse events in pediatric patients with atopic dermatitis including facial erythema and herpes simplex virus.

Recent data from Philadelphia on the monoclonal antibody dupilumab reported adverse events and an inadequate response to the biologic in pediatric patients with atopic dermatitis.

Leslie Castelo-Soccio, MD, PhD, The Children’s Hospital of Philadelphia, and colleagues considered it to be a “small but significant” number of patients.

Despite dupilumab having been approved for the use in children and adults with moderate-to-severe atopic dermatitis ≥6 years of age, certain patient groups recorded difficulties with the biologic.

With atopic dermatitis affected roughly 10%-20% of children in developed countries, Castelo-Soccio and colleagues set out to assess inadequate response and adverse events in dupilumab therapy for atopic dermatitis.

The Study

The investigators initiated the single-cohort study by identifying 291 children aged 18 years and younger with a diagnosis of atopic dermatitis who were treated with the biologic prior to April 2021.

They collected clinical data that included atopic dermatitis disease and treatment history, dupilumab dosing, and responses to dupilumab, which were evaluated in patients with ≥3 consecutive months of therapy.

Castelo-Soccio and investigators prescribed 300 mg of dupilumab every 4 weeks, 200 mg every 2 weeks, or 300 mg every 2 weeks based on patients’ weight.

Patients were also categorized based on their responses to dupilumab, either as responder, primary poor responder, or secondary poor responder.

Responders were defined as having > 50% reduction in Eczema Area and Severity Index (EASI) score. Primary poor responders had EASI scores that did not decrease by >50% after at least 3 months of dupilumab therapy, and secondary poor responders were those who initially responded to dupilumab but did not achieve stable long-term disease control with significant AD flares.

The Findings

Castelo-Soccio and investigators noted that 12 (6.3%) children were considered primary poor responders, and 4 (2.1%) were secondary poor responders.

Of the 12 primary poor responders, 3 discontinued treatments due to lack of improvement. The entirety of the secondary poor responders achieved significant improvement in the initial stage of the study, yet did not achieve long-term atopic dermatitis control and continued having severe flares.

A total of 80 children (40%) experienced 1 or more reported adverse events to dupilumab therapy.

A total of 24 children (12.0%) experienced dupilumab-associated facial erythema, while another 24 children (12.0%) had injection-site reactions from subcutaneous dupilumab administration. The latter was predominantly linked to female patients.

Conjunctivitis was recorded in a total of 21 (10.5%) of children, with patients experiencing bilateral ocular erythema, pain, and pruritis.

Concerningly, 11 children (5.5%) developed herpes simplex virus (HSV) while on dupilumab, with 6 having at least 1 episode of localized orofacial HSV, while 5 were diagnosed with eczema herpeticum. Over half (54.5%) of this affected group had an atopic dermatitis-related hospitalization in the past compared wo 16.5% recorded in the overall cohort.

Despite the high efficacy rate of dupilumab, and the biologic being considered well-tolerated, the investigators believed the risk-factors for dupilumab warranted further study.

“Dupilumab is an important therapeutic option for those with atopic dermatitis, but the risks of inadequate response to therapy or unacceptable adverse events must be discussed with patients and families prior to treatment initiation to set appropriate expectations,” the team wrote.

The study, “Experience using dupilumab for pediatric atopic dermatitis at a tertiary care c enter: Inadequate response and adverse events,” was published online in Pediatric Dermatology.