Conjunctivitis in dupilumab clinical trials

Abstract

Summary Background Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials. Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certa...

Keeping an eye on the ocular problems in dupilumab clinical trials

“…4 Allergic conjunctivitis and other ocular surface disorders are also common comorbidities of other atopic disorders such as asthma and allergic rhinitis. 2 However, the incidence rates of conjunctivitis in all asthma trials were lower than those in the AD trials. At the same time, it is difficult to compare the baseline rates of conjunctivitis across various indications in the dupilumab clinical trials, because the trials differed in data collection.…”

“…Dupilumab is a monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, thus inhibiting the signalling of both IL-4 and IL-13, and is approved for inadequately controlled moderate-to-severe atopic dermatitis (AD). [1][2][3] However, an increased incidence of conjunctivitis has been detected in patients who received dupilumab compared with those who received placebo. Ocular surface disorders, including conjunctivitis, blepharitis, keratitis, eye pruritus and dry eye, are commonly reported adverse events in dupilumab-treated patients with AD, with conjunctivitis being the most dominant one.…”

“…Ocular surface disorders, including conjunctivitis, blepharitis, keratitis, eye pruritus and dry eye, are commonly reported adverse events in dupilumab-treated patients with AD, with conjunctivitis being the most dominant one. [2][3][4][5] In this issue of the BJD, Akinlade et al 2 reviewed the results of published clinical trials and synthesized the available data on the incidence rates, disease course and associated baseline characteristics of patients who developed conjunctivitis in clinical trials of dupilumab in AD, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE).…”

“…In all of the trials, most of the cases of conjunctivitis were mild or moderate, and most resolved while continuing dupilumab treatment. 2 Furthermore, the relationship between treatment response and conjunctivitis incidence varied between treatment groups and studies. Patients who achieved high-level efficacy outcomes (Investigator's Global Assessment 0/1; 75% improvement from baseline in Eczema Area and Severity Index) in the monotherapy pool were less likely to develop conjunctivitis than those who did not achieve those outcomes.…”

New biological treatments for asthma and skin allergies

“…APC: antigen-presenting cell, TSLP: thymic stromal lymphopoietin Dupilumab also efficiently reduces pruritus and improves quality of life. Its safety profile is very high, with the exception of conjunctivitis that occurs in roughly 10% of AE patients and that requires special attention in this population 119.…”