Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome

J Allergy Clin Immunol. 2010 Oct;126(4):828-835.e3. doi: 10.1016/j.jaci.2010.06.049.


Background: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells.

Objective: To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile.

Methods: Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses.

Results: Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab.

Conclusion: Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.

Trial registration: NCT00086658.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • CD3 Complex / metabolism
  • CD4 Antigens / metabolism
  • Chemokine CCL17 / blood
  • Double-Blind Method
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Hypereosinophilic Syndrome / drug therapy*
  • Hypereosinophilic Syndrome / immunology
  • Interleukin-5 / immunology
  • Interleukin-5 / metabolism*
  • Lymphocytes
  • Male
  • Middle Aged
  • Prednisone / administration & dosage*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Treatment Outcome
  • Young Adult


  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CCL17 protein, human
  • CD3 Complex
  • CD4 Antigens
  • Chemokine CCL17
  • IL5 protein, human
  • Interleukin-5
  • mepolizumab
  • Prednisone

Associated data