Mark Lebwohl, MD

Mark G. Lebwohl, MD, the dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai,

Mark G. Lebwohl, MD, the dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai,

Articles by Mark Lebwohl, MD

Panelists discuss how Bruton tyrosine kinase (BTK) inhibitors represent a promising new therapeutic class for chronic spontaneous urticaria (CSU) by offering rapid symptom control through targeted inhibition of both mast cell and B cell pathways, with newer agents like remibrutinib showing high selectivity, favorable safety, and robust efficacy in clinical trials that could position them as an important oral therapy option between antihistamines and biologics.

Panelists discuss how remibrutinib demonstrated rapid and sustained efficacy in the REMIX-1 and -2 trials through significant improvements in disease activity scores (UAS7, ISS7, HSS7) starting at week 1 and maintained through 52 weeks, with nearly half of patients achieving complete symptom resolution (UAS7 = 0) by week 52, while maintaining a favorable safety profile throughout the study period.

Panelists discuss how pharmacological Bruton tyrosine kinase (BTK) inhibition with agents like remibrutinib appears safer than genetic BTK deficiency (X-linked agammaglobulinemia [XLA]), as clinical studies show the drug doesn't significantly impact immunoglobulin levels or infection rates in patients with chronic spontaneous urticaria (CSU), unlike the severe immunodeficiency seen in XLA.

Panelists discuss how newer Bruton tyrosine kinase (BTK) inhibitors being developed for chronic spontaneous urticaria (CSU), particularly remibrutinib (in phase 3 trials) and rilzabrutinib (in phase 2), are designed to be more selective than earlier oncology-focused BTK inhibitors, potentially reducing off-target effects like bleeding, cardiovascular complications, and GI issues.

Panelists discuss how chronic spontaneous urticaria develops through 2 distinct pathways: autoallergic CSU involving IgE-mediated mast cell activation (type I hypersensitivity) and autoimmune CSU where IgG autoantibodies target FcεRI receptors or IgE itself (type IIb hypersensitivity), both ultimately leading to mast cell degranulation and wheal formation.