Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis

  Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, systemic small- and medium-vessel vasculitis associated with asthma, blood eosinophilia and inflammation across several organs. Lung disease is common, while sinus, skin, nerve, heart and kidney involvement can determine the seriousness of an individual case.

  Mepolizumab is a targeted anti-interleukin-5 biologic that reduces eosinophil production and survival. By lowering eosinophilic inflammation, it can help control relapsing or refractory EGPA and reduce reliance on prolonged systemic corticosteroid treatment. Its place in therapy depends on disease activity, organ damage, previous medicines and the patient’s overall risk profile.

  In Australia, diagnosis and follow-up may involve a respiratory physician, rheumatologist, immunologist and other specialists. Care can be coordinated through major centres in Sydney, Melbourne, Brisbane, Perth or Adelaide, although people in regional and remote areas may need telehealth, shared-care arrangements and travel to a tertiary hospital.

  Professional education remains important because EGPA can resemble severe asthma with nasal polyps or another form of eosinophilic lung disease. Resources such as international respiratory meetings can help clinicians place biologic treatment within broader discussions about airway disease, vasculitis and multidisciplinary care.

  How EGPA Develops And Presents

  EGPA typically evolves through overlapping phases rather than following a single predictable pattern. Allergic disease, asthma and chronic rhinosinusitis may precede tissue eosinophilia and systemic vasculitis by years. Some patients develop pulmonary infiltrates, fever, weight loss or marked fatigue, while others first present with mononeuritis multiplex, purpura, gastrointestinal symptoms or cardiac inflammation.

  Antineutrophil cytoplasmic antibody status can provide useful clinical information, but a negative result does not exclude EGPA. ANCA-positive disease is often associated with features such as glomerulonephritis or peripheral neuropathy, whereas ANCA-negative patients may have more prominent eosinophilic and cardiac manifestations. Blood eosinophil counts can fluctuate and may be temporarily suppressed by corticosteroids.

  Assessment should cover organ-threatening disease, current eosinophil levels, asthma control, sinus symptoms, lung function and evidence of relapse. Cardiac screening is particularly important, as myocardial involvement may be clinically subtle. Chest imaging, urine testing, renal function, nerve assessment and echocardiography may all be relevant.

  Where Mepolizumab Fits In Treatment

  Mepolizumab binds interleukin-5, a cytokine central to eosinophil maturation and activation. The approved EGPA regimen commonly used in adults is 300 mg by subcutaneous injection every four weeks, although prescribing decisions must follow the current Australian product information and specialist guidance. It is generally considered an add-on treatment rather than a replacement for urgent induction therapy when vital organs are threatened.

  For severe or active EGPA, glucocorticoids remain important, particularly during an acute flare. Patients with major organ involvement may also require immunosuppressants such as cyclophosphamide or rituximab. Once disease control is achieved, mepolizumab may support corticosteroid reduction and help prevent further relapses, especially when eosinophilic asthma and upper-airway disease remain difficult to control.

  Clinical trial evidence has shown benefits in remission duration and steroid reduction for relapsing or refractory EGPA. The response is not uniform, and treatment should be judged by fewer flares, improved asthma and sinus control, stable organ function, reduced eosinophilia and a safer corticosteroid burden. Persistent neuropathy or established cardiac damage may not reverse simply because eosinophil counts fall.

  Comparing Treatment Roles

  Mepolizumab is most useful when eosinophilic inflammation is a major driver of recurring disease. It does not immediately treat every mechanism of vasculitis, so a patient may still need conventional immunosuppression or organ-specific therapy. A careful baseline review helps distinguish active inflammation from permanent damage, infection, medication effects and steroid withdrawal symptoms.

  Treatment approach	Main role in EGPA	Important considerations
  Systemic corticosteroids	Rapid control of inflammation and acute flares	Effective but associated with diabetes, osteoporosis, infection, hypertension and other cumulative harms
  Mepolizumab	Steroid-sparing control of eosinophilic, relapsing or refractory disease	Regular injections, delayed assessment of benefit and continued need for monitoring
  Rituximab	Selected severe or ANCA-associated disease, especially with certain organ-threatening features	Infection risk, infusion reactions and immunoglobulin monitoring
  Cyclophosphamide	Induction for severe, life-threatening or organ-threatening vasculitis	Significant toxicity, requiring careful risk assessment and limited exposure
  Asthma and sinus therapies	Control of airway symptoms and comorbid upper-airway disease	Do not substitute for treatment of systemic vasculitis

  In the Australian market, access may involve a public hospital, specialist outpatient service or private pathway. Pharmaceutical Benefits Scheme requirements, authority processes and product availability can change, so clinicians should check current Australian criteria rather than relying on older international protocols. The cost and logistics of regular injections also matter for patients who live far from a major centre.

  Safety, Monitoring And Practical Care

  Common adverse effects of mepolizumab include headache, injection-site reactions and back pain. Hypersensitivity reactions are uncommon but clinically important. Patients should be assessed for helminth infection risk where relevant, and treatment of an existing parasitic infection should be considered before starting therapy. Vaccination status, asthma medicines and infection history should be reviewed as part of routine care.

  A falling eosinophil count is useful, but it is not a complete measure of remission. Follow-up should include symptoms, examination, lung function, blood tests and organ-specific investigations. New chest pain, breathlessness out of proportion to asthma, haematuria, progressive weakness, severe abdominal pain or neurological change warrants prompt clinical review.

  For Australians, practical planning may include injection training, refrigeration requirements, appointment timing and a strategy for public holidays or travel between states. People in regional Queensland, Western Australia or the Northern Territory may need coordinated dispensing and telehealth support. Specialist teams can also consider work schedules, distance from hospital and the patient’s ability to attend four-weekly appointments.

  Building A Personalised EGPA Plan

  Treatment decisions should be shared between the patient and a team experienced in vasculitis, severe asthma and biologic medicines. A useful plan records the pattern of previous flares, affected organs, steroid exposure, eosinophil trends, vaccination needs and the warning symptoms that require urgent assessment. Respiratory education events, including the lung diseases workshop, reflect the value of cross-specialty discussion in complex pulmonary conditions.

  Patients should understand that biologic treatment is usually one part of long-term disease management. Inhaled asthma therapy, nasal treatment, pulmonary rehabilitation, bone protection and cardiovascular risk management may remain necessary. Smoking cessation support is relevant where applicable, while Australia’s bushfire smoke and seasonal pollen can aggravate respiratory symptoms even when vasculitis is controlled.

  Key considerations for clinical review include:

  • Confirm whether symptoms represent active EGPA, asthma, infection or established organ damage.
  • Check current Australian prescribing, TGA information and PBS access requirements.
  • Monitor cardiac, renal, neurological, pulmonary and upper-airway involvement over time.
  • Measure steroid reduction alongside relapse prevention and day-to-day respiratory function.
  • Coordinate care across tertiary hospitals, local doctors, pharmacists and telehealth services.

  Mepolizumab offers an important steroid-sparing option for selected adults with relapsing or refractory eosinophilic EGPA, particularly when severe asthma and persistent eosinophilia are prominent. The central point to remember is that successful treatment means controlling systemic disease and protecting organs, not simply lowering the eosinophil count.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)