Abstract

Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-siglec-8 monoclonal antibody that depletes eosinophils and inhibits mast cells.Determine safety and preliminary efficacy of lirentelimab in an open-label, Phase 1b study.Patients with chronic, severely symptomatic atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC) and perennial allergic conjunctivitis (PAC), and who had history of topical or systemic corticosteroid use were enrolled to receive up to six monthly lirentelimab infusions (Dose 1: 0.3mg/kg, Dose 2: 1mg/kg, subsequent doses: 1 or 3mg/kg). Changes from baseline of peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily allergic conjunctivitis symptom [ACS] questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (OSS), quality of life, and changes in tear cytokine and chemokine levels were assessed.Thirty patients were enrolled (AKC n=13, VKC n=1, PAC n=16), 87% of whom had atopic comorbidities. Post-lirentelimab treatment, mean improvement was observed in ACS (-61%, 95%CI:-75%, -48%) and OSS (-53%; 95%CI:-76%, -31%), consistent across AKC, VKC, and PAC groups. There was substantial improvement in atopic comorbidities, with -55% (95%CI:-78%, -31%), -50%(95%CI:-82%, -19%), and -63%(95%CI:-87%, -38%) reduction of symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears post-lirentelimab treatment. The most common AEs were mild-to-moderate infusion related reactions.Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

View details for DOI 10.1016/j.jaci.2022.03.021

View details for PubMedID 35390403