Abstract and Introduction
Abstract
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.
Introduction
Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions.[1] Ocular surface diseases, including various forms of conjunctivitis, blepharitis and keratitis, are commonly present in patients with AD, with a 2021 review reporting that 31% of patients with AD also report conjunctivitis.[2] Further evidence suggests that patients with AD who have concurrent atopic conditions have higher rates of conjunctivitis.[3,4] However, the association between type of atopic comorbidity and conjunctivitis risk has not been studied. Drug-induced conjunctivitis has been observed in clinical trials of dupilumab, a therapy that blocks interleukin (IL)-4 and IL-13 signalling via IL-4 receptor (IL-4R)α,[5,6] and has been suggested to be a drug–disease interaction.[7,8] In real-world clinical practice, the estimated prevalence of conjunctivitis in dupilumab-treated patients based on a systematic review of the literature is 26%,[9] and can be persistent, despite adequate ophthalmological treatment.[10] Additionally, the incidence of ocular complications, such as conjunctivitis, with dupilumab has been shown to increase with AD severity.[3,11] Ophthalmological side-effects during dupilumab treatment have only been observed in patients with AD and not in studies of chronic sinusitis with nasal polyps, asthma or eosinophilic oesophagitis,[12–14] suggesting AD-specific predisposing factors.
IL-13, a key driver of the underlying type 2 inflammation in AD, is overexpressed in lesional and nonlesional AD skin. Conjunctivitis signals have also been observed in phase II and phase III studies of tralokinumab and lebrikizumab, which specifically inhibit IL-13 signalling.[15–18] Tralokinumab, a fully human IgG4 monoclonal antibody, specifically binds to IL-13 with high affinity, preventing interaction with IL-13Rα1 and subsequent downstream IL-13 signalling, thus inhibiting its proinflammatory activity.[19–21] Tralokinumab has demonstrated efficacy and safety in a number of phase II and phase III trials in AD.[15,18,22,23]
Since the introduction of dupilumab as a treatment for AD, conjunctivitis has been identified as an important adverse event (AE), resulting in an increased collaboration with ophthalmologists.[24–26] Conjunctivitis was therefore recorded as an AE of special interest (AESI) in the tralokinumab phase III trials, and it is important to examine these data for insight into the incidence and profile of conjunctivitis in patients treated with tralokinumab.
The objective of this analysis was to characterize the occurrence of and risk factors for conjunctivitis in a large pool of patients with moderate-to-severe AD from five phase II/III trials of tralokinumab.
The British Journal of Dermatology. 2022;186(3):453-465. © 2022 Blackwell Publishing
