Lirentelimab Reduces Levels of Inflammatory Cytokines in Tear Fluid From Patients With Allergic Conjunctivitis
P. Asbell1; N. Roy2; A. Fernandez1; A. Kantor3; A. Chang3; B. Singh3; B. Youngblood3
1University of Tennessee Health Science Center - Health Sciences Library, Memphis, United States of America; 2Weill Cornell Medicine, New York, United States of America; 3Allakos Inc., Redwood City, United States of America
Background

Allergic conjunctivitis (AC) is an ocular inflammatory disease mediated by eosinophils and mast cells; treatments for severe AC are often ineffective or produce side effects. A phase 1b, open-label study evaluated the investigational drug lirentelimab, a monoclonal antibody against Siglec-8 that depletes eosinophils and inhibits mast cells, in patients with severe and chronic AC. To assess the effect of lirentelimab on local ocular inflammation, we measured the presence of cytokines and chemokines associated with AC in lacrimal (tear) fluid collected over the course of the study. 

Method

Adults with chronic severe atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), or perennial allergic conjunctivitis (PAC) and a history of topical or systemic corticosteroid use were given up to 6 monthly infusions (weeks 1–24) of lirentelimab (dose 1, 0.3mg/kg; dose 2, 1mg/kg; subsequent doses, 1 or 3mg/kg) and then assessed every 4 weeks during a 20-week follow-up period. Tear fluid samples were collected from the lateral part of the lower conjunctival fornix in 7 patients (2 with AKC and 5 with PAC) at baseline and on days 84, 169, and 309. We measured levels of cytokines and chemokines (CCL24, CCL11, CCL5, IL-10, CCL26, PDGF, IL-13, IL-17A, IL-33, CXCL9, IL-4, IL-23, IL-6, IL-8, IP-10, CCL2, CCL3, CCL4 and CCL17) in tear samples using a multiplex magnetic bead assay.

Results

Of the cytokines that were studies, levels of IL-4, IL-10, IL-13, IL-17A, IL-23, CCL3, CCL5, CCL11, and CCL26 in tear fluid decreased significantly after lirentelimab administration compared with baseline (see Figure). Levels of these inflammatory mediators rebounded to at least baseline levels during the follow-up period (day 309), indicating that observed decreases in these factors were associated with lirentelimab treatment.

Conclusion

Lirentelimab reduced levels of inflammatory cytokines and chemokines in tears of patients with AKC, VKC, and/or PAC. These findings provide insight into mechanisms of AC pathogenesis and indicate lirentelimab may be effective in reducing local ocular inflammation.