The Journal of Allergy and Clinical Immunology | 2019
Kinetic Profiling of Clinical Symptoms and Basophil Parameters During Treatment of Chronic Spontaneous Urticaria with Omalizumab: 146
Abstract
S A T U R D A Y Kirti J. Johal, MD, Donald W. MacGlashan, Jr, MD PhD, John T. Schroeder, PhD, Eric T. Oliver, MD, Kristin L. Chichester, MS, and Sarbjit S. Saini, MD FAAAAI; Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Omalizumab is a humanized IgG1k anti-IgE monoclonal antibody approved for treatment of chronic spontaneous urticaria (CSU). Details are lacking regarding the timing of omalizumab’s clinical effect relative to high affinity IgE receptor (FcεRI) downregulation and its function on various cell types. The purpose of this study is to examine the kinetics of clinical symptom improvement relative to basophil phenotype shifts during treatment of CSU with omalizumab. METHODS: Adults with antihistamine-refractory CSU were recruited and treated with omalizumab 300 mg monthly for 90 days, following a 2 week run-in period to establish baseline symptoms. Subjects recorded Urticaria Activity Scores (UAS) twice daily, and weekly UAS-7 scores were calculated. Clinical assessments and blood sampling occurred at baseline and days 1, 3, 6, 10, 20, 30, 60 and 90 following initial omalizumab administration. Basophil measures included manual counts, blood histamine content, histamine release response, BAT and flow cytometric analysis of surface markers (IgE, FcεRI, CRTh2). RESULTS: A 50% reduction in UAS-7 scores was achieved on average by day 136 6 (n56) after the first dose of omalizumab. At that time, basophil counts following enrichment on Percoll increased by an average of 50%. Basophil surface IgE and FcεRI were reduced by 50% by day 6. Additionally, at the time of 50% symptom reduction, CRTh2 increased by approximately 30%. CONCLUSIONS: At the time of 50% symptom reduction in baseline UAS-7 scores with omalizumab therapy, basophil surface IgE and FcεRI were reduced. Increased CRTh2 expression and blood basophils were noted at the time of CSU symptom reduction.