Use of an Anti–Interleukin-5 Antibody in the Hypereosinophilic Syndrome with Eosinophilic Dermatitis

Plötz, Sabine-Gisela; Simon, Hans‐Uwe; Darsow, Ulf; Simon, Dagmar; Vassina, Ekatherina; Yousefi, Shída; Hein, Rüdiger; Smith, T. F.; Behrendt, Heidrun; Ring, Johannes

doi:10.1056/nejmoa031261

Cited by 239 publications

(165 citation statements)

References 15 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…Another issue with corticosteroids is the problem associated with preventing the systemic effects of locally administered corticosteroids. Recent case reports in hypereosinophilic syndrome patients resistant to corticosteroid therapy, demonstrate the role of targeting the eosinophil with anti-IL-5 therapy to gain clinical improvement (98). Further, adding anti-IL-5 therapy to these patients may have a corticosteroid sparing effect (99).…”

Section: Future Direction In Asthma Therapy: the Paradigm Of Convergencementioning

confidence: 99%

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Adamko

Odemuyiwa

Vethanayagam

et al. 2004

Allergy

View full text Add to dashboard Cite

We have entered a new phase in the evolution of our understanding of the role of the eosinophil with a greater appreciation of novel potential functions that may be ascribed to this enigmatic cell type. This review not only provides an update to our current understanding of the various immunobiological roles for the eosinophil, but also attracts attention to some novel observations predicting functions beyond its putative effector role. These observations include the intriguing possibility that the eosinophil may posses the capacity to regulate the immune and inflammatory responses in diseases such as asthma.

show abstract

Section: Future Direction In Asthma Therapy: the Paradigm Of Convergencementioning

confidence: 99%

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Adamko

Odemuyiwa

Vethanayagam

et al. 2004

Allergy

View full text Add to dashboard Cite

show abstract

“…Preliminary data in patients with HES and EE treated with anti-IL-5 have revealed promising results, including improvements in clinical parameters and levels of tissue eosinophilia. [17][18][19][20] The first randomized, double-blind, placebo-controlled trial of patients with HES was recently conducted and aimed at demonstrating the ability of anti-IL-5 to decrease prednisone dependence in HES not associated with the constitutively activated tyrosine kinase FIP1L1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA). 21 Impressively, this international trial revealed a striking ability of anti-IL-5 to decrease prednisone doses, decrease blood eosinophilia, and maintain clinical stability compared with placebo.…”

Section: Introductionmentioning

confidence: 99%

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Stein

Villanueva

Buckmeier

et al. 2008

Journal of Allergy and Clinical Immunology

130

115

View full text Add to dashboard Cite

show abstract

“…Encouraging results were reported, with a rapid decline of blood eosinophil counts shortly after administration in most patients [47][48][49]. This was associated with decreased eosinophil degranulation, reflected by reduced serum eosinophil cationic protein (ECP) levels [47]. In most cases, successful eosinophil depletion in blood was associated with improvement of a wide spectrum of clinical manifestations (including rash, angioedema, mucosal ulcers, myalgia, arthralgia, dysphagia, vomiting, nasal congestion and polyposis), correlating with significant reductions of eosinophil numbers in the skin and esopha-gus of patients with eosinophilic dermatitis [47] and severe eosinophilic esophagitis [48], respectively.…”

Section: F/p-negative Hesmentioning

confidence: 95%

“…Initially, two molecules were developed for intravenous use (mepolizumab by GlaxoSmithKline and formerly SCH55700 by Schering Plough) and tested in HES patients, some of whom were corticosteroid nonresponders, in the setting of compassionate use programs. Encouraging results were reported, with a rapid decline of blood eosinophil counts shortly after administration in most patients [47][48][49]. This was associated with decreased eosinophil degranulation, reflected by reduced serum eosinophil cationic protein (ECP) levels [47].…”

Section: F/p-negative Hesmentioning

confidence: 99%

Hypereosinophilic Syndromes

Roufosse¹,

Goldman²,

Cogan³

2009

Urticaria and Angioedema, Second Edition

View full text Add to dashboard Cite

Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 × 10 9 /L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4-9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato-and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P + variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3 -CD4 + phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P + patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells.

show abstract

Use of an Anti–Interleukin-5 Antibody in the Hypereosinophilic Syndrome with Eosinophilic Dermatitis

Cited by 239 publications

References 15 publications

The rise of the phoenix: the expanding role of the eosinophil in health and disease

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels

Hypereosinophilic Syndromes

Contact Info

Product

Resources

About