The recognized comorbidity of atopic dermatitis is conjunctivitis. Dupilumab clinical studies in adults with moderate-to-severe atopic dermatitis revealed a greater incidence of conjunctivitis in dupilumab-treated patients than in placebo-treated patients, although trials in uncontrolled asthma revealed reduced rates for both dupilumab and placebo. For a study, researchers wanted to assess the frequency and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma. In three phase III studies, researchers looked at the prevalence of conjunctivitis in teenagers (aged 12 to 18 years). Ocular events were identified and treated by research investigators based on patient-reported symptoms and an external eye examination, in most instances without an ophthalmologic referral. Adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients 60 kg at baseline; 300 mg, patients 60 kg at baseline) in the LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blind trial). Pediatric patients from prior dupilumab atopic dermatitis studies were given dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks in the LIBERTY AD PED-OLE (open-label extension). Patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on treatment with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo in the LIBERTY ASTHMA QUEST (randomized, double-blind, placebo-controlled trial).
In ADOL, more dupilumab (17/165; 10.3%than placebo (4/85; 4.7%) patients had one or more conjunctivitis events. All of the incidents were mild to moderate in severity, and 12 (7.3%) of the dupilumab-treated patients and 4 (4.7%) of the placebo-treated patients received therapy. During the therapy period, the majority of patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved. The risk of conjunctivitis has no association with the serum levels of dupilumab. In the PED-OLE study, 12/275 teenagers (4.4%) reported one or more episodes of conjunctivitis. The majority of conjunctivitis cases were mild to severe. Conjunctivitis was treated in ten individuals. During the course of the trial, ten patients recovered/resolved. In QUEST, comparably low numbers of adolescents treated with dupilumab (2/68, 2.9%) and placebo (1/39, 2.6%) experienced one or more conjunctivitis events. All of the occurrences were mild to moderate in nature. Conjunctivitis was treated in one dupilumab-treated patient. During the research, all instances were recovered and resolved. Conjunctivitis did not lead any patients in these studies to stop taking their medication, either temporarily or permanently. In ADOL, one case of unspecified viral keratitis (specific viral etiology unknown) was reported in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis was reported in the placebo group; both events resolved during the treatment period and neither resulted in treatment discontinuation.
In atopic dermatitis trials, dupilumab-treated adolescents had a higher rate of conjunctivitis than placebo-treated patients, whereas, in asthma trials, overall rates of conjunctivitis among adolescents were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. The majority of the incidents were minor to moderate, and the majority of them were recovered/resolved. None of them necessitated the study’s termination.
Reference:link.springer.com/article/10.1007/s40257-020-00577-1
