Mepolizumab in patients with lymphoid variant hypereosinophilic syndrome: a multi-center prospective study.

Background: Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia causing organ damage and/or dysfunction. Mepolizumab, an anti-IL-5 antibody, has recently been approved in this indication. In lymphoid variant (L-)HES, eosinophil expansion is driven by IL-5-producing clonal CD3CD4 T cells.

Hypereosinophilic syndrome response to mepolizumab in the setting of a compassionate use program.

Mepolizumab, an anti-interleukin-5 antibody, has been proven a safe and effective glucocorticoid (GC)-sparing drug for many patients with nonclonal hypereosinophilic syndrome (HES) and is now approved in many countries. It remains unclear, however, which patients are most likely to benefit from therapy and whether the currently approved dosing regimen is appropriate for all. This observational retrospective study included all patients with HES who were enrolled in the MHE104317 compassionate use program (CUP) in our center.

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult.

Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA.

Methods: We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab.

Case report: Serious unexpected vascular events in two patients with lymphocytic variant hypereosinophilic syndrome.

Background: Lymphocytic-variant hypereosinophilic syndrome (L-HES) is a form of reactive hypereosinophilia, most commonly associated with interleukin-5 over-production by clonal, most commonly CD3CD4CD2CD5CD45RO T-cells. Patients often present with predominant cutaneous and soft-tissue manifestations, while cardiovascular involvement is uncommon.

Methods: We reviewed the medical files of two L-HES patients followed in our center who developed serious vascular complications and performed a literature review for similar cases.

HES and EGPA: Two Sides of the Same Coin.

Elevated eosinophil counts are implicated in multiple diseases, from relatively prevalent organ-specific disorders such as severe eosinophilic asthma, to rare multisystem disorders such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA). Patients with these multisystem diseases, often associated with markedly elevated eosinophil counts, have a substantial risk of morbidity and mortality due to delayed diagnosis or inadequate treatment. A thorough workup of symptomatic patients presenting with elevated eosinophil counts is essential, although in some cases the differential diagnosis may remain difficult because of overlapping presentations between HES and EGPA.

Plain Language Summary of principles for improving the care of people with eosinophil-associated diseases.

Eosinophil-associated diseases (EADs) are a group of conditions in which eosinophils (a type of white blood cell) are thought to play a key role in the disease and how it develops. Some EADs are common, such as atopic dermatitis (also called eczema) and a subtype of asthma called eosinophilic asthma, while others are rare, such as hypereosinophilic syndrome (a condition in which a person has a very high number of eosinophils in both the blood and one or more organs). People with EADs face many problems related to their conditions.

Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes.

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES.

Improving Care in Eosinophil-Associated Diseases: A Charter.

Eosinophil-associated diseases (EADs) are a range of heterogeneous conditions in which eosinophils are believed to play a critical pathological role. EADs include common illnesses such as eosinophilic asthma and chronic rhinosinusitis and rare conditions such as hypereosinophilic syndromes (HES) and eosinophilic gastrointestinal disorders (EGIDs). EADs are associated with substantial burdens for the patient, including chronic, debilitating symptoms, increased financial burden, decreased health-related quality of life, and the need for repeated visits to multiple different healthcare professionals (HCPs), emergency departments, and/or hospitals.

An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes.

Background: Treatment of hypereosinophilic syndrome (HES) often requires the use of immunomodulators with substantial side effect profiles. The emergence of biologics offers an alternative treatment modality.

Objective: To examine real-world practice data to describe the safety and consequences of various biologics suspected to directly or indirectly affect eosinophilic inflammation for the treatment of HES.

From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases.

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects.

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study.

Background: A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year.

Objective: To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab.

Methods: Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks.

Hypereosinophilic syndrome: considerations for the cardiologist.

Eosinophil-mediated endomyocardial damage is a well-known complication in patients with hypereosinophilic syndromes (HES). Although management and survival have improved significantly, some patients continue to develop severe cardiomyopathy as a direct consequence of uncontrolled hypereosinophilia. Cardiologists play a key role in early detection and treatment.

CD3CD4 Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited.

Background: Identification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications.

Objective: This study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations.

Methods: Biomarkers of T-cell-driven disease were compared between patients with L-HES versus idiopathic HES (I-HES) variants.

Eosinophilia Associated With CD3CD4 T Cells: Characterization and Outcome of a Single-Center Cohort of 26 Patients.

Lymphocytic variant hypereosinophilic syndrome is characterized by marked over-production of eosinophilopoietic factor(s) by dysregulated T cells leading to eosinophil expansion. In most cases, these T cells are clonal and express a CD3CD4 phenotype. As this is a rare disorder, presenting manifestations, disease course, treatment responses, and outcome are not well-characterized.