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)

• Biologics in severe asthma: a comparative review

  Severe asthma remains uncontrolled despite high-dose inhaled corticosteroids, a long-acting bronchodilator and careful attention to adherence, inhaler technique and triggers. For these patients, biologic medicines can reduce exacerbations, oral corticosteroid exposure and urgent healthcare use by targeting specific inflammatory pathways rather than broadly suppressing the immune system.

  The major options available in specialist practice include omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab. Their clinical roles overlap, but their eligibility criteria, dosing schedules, biomarkers, age approvals and practical administration requirements differ. A sound comparison therefore needs to look beyond headline trial results.

  Australian decisions are shaped by local realities. Patients may move between metropolitan respiratory clinics in Sydney, Melbourne, Brisbane or Perth and services with fewer specialist appointments in regional areas. Bushfire smoke, household dust, mould, pollens and occupational exposures can all aggravate symptoms, while the Therapeutic Goods Administration (TGA) and Pharmaceutical Benefits Scheme (PBS) influence which treatments can be prescribed and subsidised.

  Defining severe asthma beyond poor control

  Severe asthma is generally diagnosed when symptoms and exacerbations remain uncontrolled despite optimised treatment, or when control can be maintained only with high-dose inhaled corticosteroids plus additional controllers or maintenance oral corticosteroids. Before escalating to a biologic, clinicians should confirm the diagnosis and address modifiable factors such as incorrect inhaler use, missed doses, smoking or vaping, untreated rhinitis, reflux, obesity and ongoing allergen exposure.

  Phenotyping is central. Type 2 inflammation may be suggested by raised blood eosinophils, increased fractional exhaled nitric oxide, allergic sensitisation or a history of atopic disease. Some patients have predominantly allergic asthma, some have eosinophilic disease, and others show mixed features. Biomarkers can fluctuate after corticosteroid treatment, so a single low eosinophil count should not automatically exclude a targeted therapy.

  Environmental management remains relevant even when a biologic is selected. Allergen immunotherapy may have a place for carefully selected respiratory allergy patients, although it is not a substitute for biologic treatment in uncontrolled severe asthma; allergen immunotherapy should be considered within a specialist assessment of sensitisation, asthma stability and anaphylaxis risk.

  How biologics target airway inflammation

  Omalizumab binds circulating immunoglobulin E and is primarily used for allergic asthma, with dosing determined by body weight and baseline IgE. It can reduce exacerbations in appropriately selected patients with perennial allergen sensitisation. Its dose calculations and injection frequency can be inconvenient, and a history of severe allergic reactions requires careful observation.

  Mepolizumab and reslizumab inhibit interleukin-5, while benralizumab targets the interleukin-5 receptor and produces marked eosinophil depletion. These medicines are most relevant to eosinophilic asthma, particularly where recurrent exacerbations or dependence on oral corticosteroids indicate substantial eosinophil-driven disease. Reslizumab is administered intravenously in many settings, whereas mepolizumab and benralizumab are given by injection.

  Dupilumab blocks signalling through interleukin-4 and interleukin-13, making it useful for Type 2 asthma with raised eosinophils or exhaled nitric oxide. It may be especially attractive when the patient also has atopic dermatitis or chronic rhinosinusitis with nasal polyps. Tezepelumab inhibits thymic stromal lymphopoietin, an upstream epithelial cytokine, and has shown benefit across a broader range of biomarker profiles, although response is often stronger when Type 2 markers are elevated.

  Comparing outcomes, risks and practical use

  Across pivotal studies, biologics commonly reduce severe exacerbations by roughly half, although individual responses vary widely. Some patients experience a major fall in maintenance prednisolone use, while others mainly notice fewer emergency visits or improved daily function. Improvements in lung function may be modest compared with the reduction in attacks, so treatment success should be assessed against the patient’s baseline rather than spirometry alone.

  Adverse effects are usually manageable, with injection-site reactions, headache, sore throat and transient fatigue among reported problems. Eosinophil-directed treatments can rarely be associated with hypersensitivity or other immune complications. Dupilumab may cause conjunctivitis or transient eosinophilia, and omalizumab carries a rare risk of anaphylaxis. Vaccination status, parasitic infection risk, pregnancy plans and comorbid nasal or skin disease should be included in the safety discussion.

  Australian access adds another layer. PBS authority requirements can involve documented exacerbations, specialist confirmation, biomarker thresholds and evidence of optimised standard therapy. Criteria and listed indications may change, so prescribing teams should verify current PBS and TGA information rather than relying on an old hospital protocol. Home administration may reduce travel for some patients, but storage, training and reliable follow-up remain essential.

  Selecting a biologic in Australian practice

  The best initial choice usually reflects the dominant phenotype, the patient’s treatment goals and the practical burden of administration. A person in regional New South Wales who cannot easily attend an infusion centre may favour a longer-interval injectable option, provided it matches the clinical indication. Someone in Melbourne with severe asthma and nasal polyps may value a therapy that addresses both lower and upper airway disease.

  Local habits and exposures should be reviewed alongside biomarkers. Weekend cycling during high-pollen periods, indoor heating, workplace chemicals, mould after flooding and exposure to bushfire smoke may contribute to poor control. A biologic should not be used to compensate for preventable exposure, but persistent disease after these factors are managed strengthens the case for advanced therapy.

  Useful prescribing and monitoring principles include:

  • Confirm severe asthma after checking diagnosis, adherence and inhaler technique.
  • Record exacerbations, hospital presentations and oral corticosteroid courses over the previous year.
  • Repeat or review eosinophil counts and exhaled nitric oxide when corticosteroids may have altered results.
  • Match the drug to allergic, eosinophilic, Type 2-high or less biomarker-dependent disease.
  • Consider comorbid nasal polyps, eczema, food allergy and steroid-related complications.
  • Discuss injection frequency, observation requirements, travel distance and home-dosing capability.
  • Set a review date with explicit goals for exacerbations, symptoms, lung function and steroid reduction.

  Measuring response and making a durable decision

  Biologic therapy should begin with a written baseline. Document symptom control, reliever use, spirometry, exacerbation history, maintenance steroid dose, eosinophils or exhaled nitric oxide and relevant comorbidities. After initiation, a review at approximately four to six months can establish whether the treatment is producing meaningful benefit, followed by regular reassessment.

  A response may be clear even if every outcome does not improve. Fewer emergency presentations, the ability to stop prednisolone, improved sleep or better tolerance of exercise can matter more than a small change in FEV1. Conversely, persistent symptoms caused by dysfunctional breathing, bronchiectasis, vocal cord dysfunction or untreated rhinosinusitis should prompt diagnostic review rather than automatic switching.

  Biologic	Main target or phenotype	Typical practical advantage	Key consideration
  Omalizumab	Allergic, IgE-mediated asthma	Established option for allergic disease	Weight and IgE guide dosing; observe for rare anaphylaxis
  Mepolizumab	Eosinophilic asthma	Subcutaneous dosing and steroid-sparing potential	Benefit depends on eosinophilic activity
  Reslizumab	Eosinophilic asthma	Intravenous delivery may suit selected patients	Infusion setting and weight-based dosing
  Benralizumab	Eosinophilic asthma	Long dosing interval after loading	Marked eosinophil depletion; confirm eligibility
  Dupilumab	Type 2 asthma, eczema or nasal polyps	Addresses several Type 2 conditions	Monitor conjunctival symptoms and eosinophilia
  Tezepelumab	Broad severe asthma population	Can help when classic biomarkers are low	Response may still be stronger with Type 2 features

  A practical next step is to bring the patient’s exacerbation record, current medicines, biomarker results and comorbidity history to a respiratory specialist review, then document one clearly defined biologic outcome to assess at the first follow-up.

  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)