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Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

ABSTRACT: Glucocorticoids (GCs) are considered first-line treatment for platelet-derived growth factor ? (PDGFRA)-negative hypereosinophilic syndromes (HESs). Despite this, little is known about clinical predictors of GC responsiveness in HES.Knowledge of clinical and laboratory predictors of GC response before initiation of GC could lead to more rational selection of subjects with HES for whom earlier institution of second-line and alternative therapies would be appropriate.Response to GC, as defined by the reduction of the absolute eosinophil count to below 1000/mm3 and control of symptoms, was assessed by a retrospective chart review of subjects with PDGFRA-negative HES evaluated on an institutional review board-approved protocol. Demographic, clinical, and laboratory parameters obtained before institution of GC, as well as final diagnosis, were evaluated to determine predictors of GC response. Proportional odds models were used for univariate and multivariate assessment of predictors with permutation adjusted P values to correct for multiple comparisons.A total of 164 subjects with PDGFRA-negative HES were categorized according to GC response. Of them, 39% of the subjects responded to low dose (?10 mg) prednisone, 9% did not respond to GC, and the remainder (52%) had variable responses to GC. The HES subtype diagnosis was the best predictor of response to GC with myeloid forms and lymphocytic variants of HES being the least responsive to GC.In a large cohort of well-characterized subjects with HES, the odds of response to GC was predicted by HES subtype. Using this model, clinicians may more readily proceed to second-line agents in subjects with confirmed lymphocytic or myeloid forms of HES.

SUBMITTER: Khoury P

PROVIDER: S-EPMC5760470 | biostudies-other | 2018 Jan - Feb

REPOSITORIES: biostudies-other

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Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

Khoury Paneez P Abiodun Annalise O AO Holland-Thomas Nicole N Fay Michael P MP Klion Amy D AD

The journal of allergy and clinical immunology. In practice 20170727 1

<h4>Background</h4>Glucocorticoids (GCs) are considered first-line treatment for platelet-derived growth factor α (PDGFRA)-negative hypereosinophilic syndromes (HESs). Despite this, little is known about clinical predictors of GC responsiveness in HES.<h4>Objective</h4>Knowledge of clinical and laboratory predictors of GC response before initiation of GC could lead to more rational selection of subjects with HES for whom earlier institution of second-line and alternative therapies would be appro ...[more]

PMID: 28757367

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Project description:BackgroundHypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils.MethodsIn this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient's background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12.ResultsDuring the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse.ConclusionsIn this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.).

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Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

Publications

Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

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