Conjunctivitis in adult patients with moderate‐to‐severe atopic dermatitis: results from five tralokinumab clinical trials

• Published in: British journal of dermatology (1951) Vol. 186; no. 3; pp. 453 - 465
• Main Authors: Wollenberg, A., Beck, L.A., Bruin Weller, M., Simpson, E.L., Imafuku, S., Boguniewicz, M., Zachariae, R., Olsen, C.K., Thyssen, J.P.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2022
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Atopic dermatitis; Clinical trials; Conjunctivitis; Conjunctivitis - epidemiology; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - epidemiology; Eczema; Hay fever; Humans; Immunoglobulin G; Keratoconjunctivitis; Monoclonal antibodies; Patients; Placebos; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.20810

Summary Background Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin‐13, effectively reduces moderate‐to‐severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. Objective To analyse conjunctivitis data recorded in five randomized, placebo‐controlled trials of tralokinumab in adult patients with moderate‐to‐severe AD. Methods Overall, 2285 adults with AD were studied up to 16 weeks. Cochran–Mantel–Haenszel weights were applied to calculate the adjusted incidence of adverse events. Results The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitations This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. Conclusions Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient. What is already known about this topic? Ocular disorders, including conjunctivitis, occur more frequently in patients with atopic dermatitis (AD). When using the interleukin (IL)‐4 and IL‐13 receptor blocking biologic dupilumab, patients with AD in clinical trials and real‐world practice experience higher rates of conjunctivitis, which increases with baseline AD severity. Tralokinumab, a fully human monoclonal antibody, binds specifically to IL‐13 with high affinity. Various rates of conjunctivitis have been observed in different clinical trials of tralokinumab. What does this study add? This is the first investigation of conjunctivitis in phase III studies of a biological drug specifically targeting IL‐13, in contrast to dupilumab, which targets the IL‐4 and IL‐13 receptors The incidence of conjunctivitis was higher with tralokinumab (7·5%) vs. placebo (3·2%); most cases were mild and resolved, or were resolving during study treatment. Risk factors included high AD severity, history of conjunctivitis, disease biomarker levels, and number and type of atopic comorbidities This is the first study to show that some atopic comorbidities have a greater influence on the risk of conjunctivitis than others. Linked Comment: R. Nguyen. Br J Dermatol 2022; 186:391–392.