ELEVATED EOSINOPHILS PLAY A KEY ROLE IN HES

Each patient with hypereosinophilic syndrome (HES) may present differently, and since HES is a rare disease (estimated prevalence of 5000 in the US*), it may be more difficult to diagnose.1,2 A thorough workup is essential for evaluating a patient who is presenting with hypereosinophilia.1,3 Below are some factors to consider when identifying patients with HES.

  • *

    Estimate based on the National Hospital Discharge Survey of ~6000 discharges with at least 1 discharge diagnosis with the ICD code for eosinophilia; ~2000 cases were compatible with HES. The ratio of outpatients to inpatients (2.5:1) from a US claims database was applied to determine the final estimate.2

EGPA vs HES

Hear from a peer | 9:06

An expert in allergy and immunology describes how to differentiate two diseases related to peripheral blood eosinophilia: eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES).

Defining hypereosinophilic syndrome4

Peripheral blood hypereosinophilia (>1500 cells/μL) on 2 exams (interval ≥1 month†)

and

Eosinophil-mediated organ dysfunction and/or damage

and

Exclusion of other disorders as a major reason for organ damage

†Diagnosis can be made immediately to avoid delay in therapy in the case of life-threatening organ damage.

Clinical manifestations vary depending on organ involvement1,5

All HES patients are different. Patients may present with single- or multiple-organ involvement. Organs and organ systems that may be impacted by HES include:

Diagram depicting organs and organ systems that may be impacted by hypereosinophilic syndrome (HES)

Differentiating HES from EGPA

Characteristics and clinical manifestations of HES overlap with those of eosinophilic granulomatosis with polyangiitis (EGPA). See below for similarities and differences between these two conditions.3

  Features of HES include:   Features of EGPA include:
  Peripheral blood hypereosinophilia (>1500 cells/μL on ≥2 occasions at least 1 month apart)4   Eosinophilia >10%6
  Vasculitic complications are rare6   Eosinophil-rich, necrotizing granulomatous vasculitis affecting small- to medium-sized vessels7
  Pulmonary manifestations occur; presence of asthma and nasal polyps is rare6   Frequent asthma and nasal polyps6
  ANCA-negative6   ~40% of patients have ANCA antibodies8,9
  Patients may experience systemic manifestations   Patients may experience systemic manifestations

LEARN ABOUT NUCALA IN EGPA 

EOSINOPHIL REDUCTION AND MECHANISM OF ACTION (MOA)

See the results of NUCALA in eosinophil reduction.

VIEW EOSINOPHIL DATA AND MOA

FLARE DATA

Proportion of patients with flares and time to first flare

REVIEW THE DATA

INDICATIONS & IMPORTANT SAFETY INFO

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

NUCALA is indicated for the: 

  • treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for greater than or equal to 6 months without an identifiable non-hematologic secondary cause.
  • add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.
  • add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients aged 18 years and older with inadequate response to nasal corticosteroids.
  • add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm.
  • treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Known hypersensitivity to mepolizumab or excipients.

 

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (ie, days). Discontinue if a hypersensitivity reaction occurs.

 

Acute Symptoms of Asthma or COPD or Acute Deteriorating Disease

NUCALA should not be used to treat acute symptoms or acute exacerbations of asthma or COPD, or acute bronchospasm.

 

Opportunistic Infections: Herpes Zoster

Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.

 

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

 

Parasitic (Helminth) Infection

Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.

 

ADVERSE REACTIONS

Most common adverse reactions (≥5%):

  • Severe asthma trials: headache, injection site reaction, back pain, fatigue
  • CRSwNP trial: oropharyngeal pain, arthralgia
  • COPD trials: back pain, diarrhea, cough
  • EGPA and HES trials (300 mg of NUCALA): most common adverse reactions were similar to severe asthma

Systemic reactions, including hypersensitivity, occurred in clinical trials in patients receiving NUCALA. Manifestations included rash, pruritus, headache, myalgia, flushing, urticaria, erythema, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, stridor, angioedema, and multifocal skin reaction. A majority of systemic reactions were experienced the day of dosing.

 

USE IN SPECIFIC POPULATIONS

The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.

 

Please see full Prescribing Information and Patient Information for NUCALA.

PMUS-MPLWCNT240088 May 2025

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Roufosse FE, Goldman M, Cogan E. Hypereosinophilic syndromes. Orphanet J Rare Dis. 2007;2(37):1-12.
  2. Wilkins HJ, Crane MM, Copeland K, Williams WV. Hypereosinophilic syndrome: an update. Am J Hematol. 2005;80(2):148-157.
  3. Leurs A, Chenivesse C, Lopez B, et al. C-Reactive protein as a diagnostic tool in differential diagnosis of hypereosinophilic syndrome and antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol Pract. 2019;7(4):1347-1351.
  4. Valent P, Klion AD, Horny H-P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012;130(3):607-612.e9.
  5. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124(6):1319-1325.e3.
  6. Vaglio A, Buzio C, Zwerina J. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art. Allergy. 2013;68(3):261-273.
  7. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1-11.
  8. Groh M, Pagnoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med. 2015;26(7):545-553.
  9. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013;65(1):270-281.