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Biologics are a newer kind of medicine — usually a small injection every few weeks — that switches off one precise signal in the immune system that drives severe asthma and some related lung conditions. Older asthma treatment leaned on a reliever puffer (salbutamol, the blue one) to open the airways in the moment, and repeated courses of prednisolone tablets to calm bad flare-ups. Biologics work further upstream: instead of firefighting each attack, they quieten the inflammation that starts the fire. For the right person they mean far fewer flare-ups, far less prednisolone, and often a real jump in day-to-day breathing and activity.
For decades, the story of asthma care was the same for almost everyone: a preventer inhaler, a blue reliever for symptoms, and — when symptoms worsened — a burst of oral steroid (prednisolone, or the closely related prednisone), sometimes many times a year. That approach still helps most people. But a minority have severe asthma that stays out of control despite high-dose inhalers taken correctly, and they paid a heavy price in emergency visits, hospital stays and the long-term harm of repeated steroids. Biologics were built for exactly this group. This guide explains — first in everyday language for patients, then in a full evidence summary for clinicians — how these medicines work, who they help, how well they work, and why physiotherapy still matters just as much once someone is on one.
Health professional? Jump to the clinical evidence summary ↓
The shift away from salbutamol and prednisolone
Understanding biologics is easier if you understand what they replaced — or rather, what they added. Three tools sat at the centre of asthma care for a long time:
- Reliever inhalers (salbutamol): fast-acting "rescue" puffers that relax the airway muscle for a few hours. They ease symptoms but do nothing about the underlying inflammation — using a lot of reliever is a warning sign that asthma is not controlled.
- Preventer inhalers (inhaled corticosteroids): daily anti-inflammatory puffers that are the foundation of good asthma control for most people, and remain so.
- Oral steroids (prednisolone, or prednisone): powerful tablets used in short bursts to settle a flare, and sometimes taken every day in severe disease. They work — but repeated or long-term use carries real harm (weight gain, diabetes, thinning bones, cataracts, high blood pressure, mood changes and more).
The modern change is a recognition that severe asthma is not one disease but several, driven by different types of inflammation. Rather than turning up the same blunt treatments, doctors can now test which inflammatory pathway is active in a particular person and pick a biologic that blocks exactly that pathway. The goal has shifted from simply controlling symptoms to getting people off long-term prednisolone and preventing flare-ups altogether.
Salbutamol and prednisolone are not "bad" — they remain essential, and everyone with asthma should still have a reliever and an action plan. What has changed is that for severe asthma we no longer have to rely on ever-higher steroid doses to stay ahead of the disease. Biologics offer a way to control the inflammation at its source, which is why they are one of the biggest advances in respiratory medicine in a generation.
What are biologics?
"Biologic" means the medicine is a large, complex protein grown in living cells, rather than a small chemical made in a factory (like most tablets). The biologics used in asthma are monoclonal antibodies — laboratory-made antibodies designed to lock onto one specific molecule in the immune system and switch it off. Because they are so targeted, they tend to leave the rest of the immune system largely alone, which is part of why they are generally well tolerated.
They are given by injection under the skin (subcutaneous), usually into the tummy, thigh or upper arm, every two to eight weeks depending on the medicine. Some are given in clinic; several can be taught for self-injection at home. They are not puffers and are not a replacement for your daily preventer inhaler — they are an add-on for severe disease.
What conditions do they treat?
In the lungs, the biggest use by far is severe asthma. They are also used in several overlapping conditions where the same type of inflammation is at work:
- Severe asthma — the main use, when high-dose inhalers plus good technique are not enough.
- Chronic rhinosinusitis with nasal polyps — inflammation of the nose and sinuses that very often travels with severe asthma.
- COPD with a specific "type-2" inflammatory signature — a newer use, for a subset of people with chronic bronchitis and raised blood eosinophils.
- Rarer conditions such as eosinophilic granulomatosis with polyangiitis (EGPA) and allergic bronchopulmonary aspergillosis (ABPA).
How doctors choose which one
This is the clever part. Before starting a biologic, the team runs simple tests — usually a blood test for eosinophils (a type of white blood cell involved in allergic inflammation), a breath test called FeNO, and sometimes an IgE (allergy) level. These "biomarkers" reveal which inflammatory pathway is driving the asthma, and therefore which biologic is most likely to help. It is a genuinely personalised choice — two people with equally severe asthma may be matched to different medicines.
What to expect on treatment
- Fewer and milder flare-ups. The clearest benefit is a large drop in the number of asthma attacks needing prednisolone or hospital care.
- Less prednisolone. Many people on daily oral steroids can reduce or stop them — one of the most important goals, because it removes years of steroid side-effects.
- Better breathing and activity. Lung function and day-to-day symptoms usually improve, though this varies.
- It takes a little time. Benefits build over weeks to a few months; the team reviews response (often at around four months) before committing long-term.
- Not everyone responds fully. A proportion are "super-responders"; others improve modestly; a few not at all — in which case a different biologic may be tried.
Safety and side-effects
Biologics are generally well tolerated. The most common issues are mild:
- Injection-site reactions — redness, soreness or itching where the needle went in.
- Headache, and occasionally a sore throat or cold-like symptoms.
- Allergic reactions are uncommon but possible; the first doses are often given where you can be observed for a short time afterwards.
Your specialist team will discuss the specific cautions for your medicine (for example, checking for past hepatitis or parasitic infection with some agents). Because these are add-on treatments, you keep taking your usual preventer inhaler unless told otherwise.
Where physiotherapy fits in
A common misunderstanding is that a biologic "fixes" everything and other care can stop. In reality, the opposite is often true — as inflammation settles, other treatable problems become clearer and more worth addressing:
- Breathing pattern problems (dysfunctional or over-fast breathing) frequently sit alongside severe asthma and can keep someone breathless even when the asthma itself is controlled. Breathing retraining helps.
- Deconditioning from years of limited activity responds to a graded exercise and rehabilitation programme.
- Airway clearance remains important where there is mucus or coexisting bronchiectasis.
- Confidence and self-management — using the improved window of control to rebuild fitness and activity is exactly where our team adds value.
Biologic therapy for severe asthma is initiated and monitored by a respiratory physician or clinical immunologist. Where treatment achieves better disease control, that period of stability is when exercise reconditioning and breathing retraining are most effective — see cardiorespiratory physiotherapy for what that involves.
A clinician-level synthesis of the phenotype-driven approach to severe asthma, the pivotal randomised trials, oral-corticosteroid-sparing and exacerbation data, biologic selection, the extension into COPD, and the implications for physiotherapy and allied health. Prepared July 2026. This is a reference summary, not a prescribing protocol.
1 · The paradigm shift: from bronchodilation to endotype-directed therapy
Historically, escalating asthma meant escalating suppression: more short-acting β2-agonist (SABA) for symptoms, higher-dose inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), and recurrent or maintenance oral corticosteroids (OCS) for the uncontrolled tail.1 Two shifts overturned this. First, SABA-only reliever use is now recognised as a marker of risk, and GINA no longer recommends SABA-only treatment — even mild asthma is managed with anti-inflammatory reliever therapy.1 Second, severe asthma is understood as a set of endotypes defined by the dominant inflammatory pathway, most usefully dichotomised into type-2 (T2)-high and T2-low disease.2,3 The six licensed respiratory biologics all target T2 inflammation, and the clinical task has become one of phenotyping and matching rather than blunt dose escalation.
These agents are monoclonal antibodies that block or deplete a defined cytokine, receptor or cell lineage. "Type-2 inflammation" denotes the IL-4/IL-5/IL-13 axis driven by Th2 lymphocytes and group-2 innate lymphoid cells (ILC2), upstream of which sit the epithelial alarmins TSLP, IL-33 and IL-25.
2 · The type-2 inflammatory cascade — where each biologic acts
The rationale for biomarker-directed selection follows directly from the cascade: an inhaled trigger or allergen activates the airway epithelium to release alarmins, which drive ILC2 and Th2 responses, generating IL-4, IL-5 and IL-13. These effectors produce eosinophilia, IgE class-switching, mucus hypersecretion and airway hyper-responsiveness. Each biologic interrupts the cascade at a different level:
3 · The agents at a glance
| Agent | Target | Route / interval | Key T2 biomarker niche | Respiratory indications |
|---|---|---|---|---|
| Omalizumab | Anti-IgE | SC q2–4 wk (weight/IgE-dosed) | Allergic, IgE 30–1500 IU/mL, perennial aeroallergen sensitisation | Severe allergic asthma; CRSwNP; CSU (non-resp) |
| Mepolizumab | Anti-IL-5 | SC 100 mg q4 wk | Blood eos ≥150–300 cells/µL | Severe eosinophilic asthma; EGPA; HES; CRSwNP |
| Reslizumab | Anti-IL-5 | IV q4 wk (3 mg/kg) | Blood eos ≥400 cells/µL | Severe eosinophilic asthma |
| Benralizumab | Anti-IL-5Rα (eosinophil-depleting, ADCC) | SC q4 wk ×3 then q8 wk | Blood eos ≥300 cells/µL | Severe eosinophilic asthma; EGPA |
| Dupilumab | Anti-IL-4Rα (blocks IL-4 & IL-13) | SC q2 wk | Blood eos ≥150 and/or FeNO ≥25 ppb; OCS-dependent regardless | Severe T2 asthma; CRSwNP; COPD with T2 inflammation; atopic dermatitis |
| Tezepelumab | Anti-TSLP (upstream alarmin) | SC q4 wk | Broad — benefit across eosinophil strata, no threshold required | Severe asthma (T2-high and some T2-low) |
Biomarker niches are indicative and reflect trial enrichment and Australian PBS criteria; exact thresholds change — verify current PBS eligibility and TGA product information before prescribing.4
4 · Efficacy — exacerbation reduction
Across the pivotal phase-3 programmes, add-on biologics reduced clinically significant exacerbations by roughly one-third to two-thirds versus placebo on optimised background therapy, with the largest effects in biomarker-enriched populations.3 Representative annualised exacerbation-rate reductions:
5 · Efficacy — the oral-corticosteroid-sparing endpoint
For the OCS-dependent phenotype, the most clinically meaningful outcome is elimination of maintenance steroid and its cumulative toxicity.10 Three dedicated double-blind steroid-reduction RCTs establish a class effect:
| Trial (agent) | Design | Median reduction in daily OCS dose | Eliminated OCS entirely |
|---|---|---|---|
| SIRIUS (mepolizumab)11 | 135 pts, 20 wk, protocolised taper | 50% vs 0% placebo (OR for reduction 2.39) | 14% vs 8% |
| ZONDA (benralizumab)12 | 220 pts, 28 wk | 75% vs 25% placebo | 52% vs 19% |
| VENTURE (dupilumab)13 | 210 pts, 24 wk | 70% vs 42% placebo | 48% off OCS |
Cumulative OCS exposure is dose-dependently associated with type-2 diabetes, osteoporosis and fracture, cataract, hypertension, adrenal suppression and infection.10 Even relatively low cumulative doses (the equivalent of ~4 lifetime OCS courses, or ≥0.5–1 g cumulative prednisolone) raise these risks. Removing maintenance OCS is therefore a hard, patient-relevant outcome — not a surrogate — and is the strongest argument for early biologic referral in the steroid-dependent patient.
6 · Pivotal trial evidence by agent
- Omalizumab (anti-IgE). The oldest agent; INNOVATE and pooled analyses show reduced exacerbations in severe allergic asthma, with the largest benefit in those with higher baseline exacerbation risk and T2 markers.5,14
- Mepolizumab (anti-IL-5). DREAM established the eosinophil-driven rationale;15 MENSA showed ~50% exacerbation reduction and improved control;6 SIRIUS demonstrated OCS-sparing.11 MIRRA extended benefit to EGPA.16
- Benralizumab (anti-IL-5Rα). SIROCCO and CALIMA showed exacerbation reduction and FEV1 gain in eosinophil-high patients;7,17 ZONDA produced the largest OCS-sparing effect of the class.12 Its antibody-dependent cell-mediated cytotoxicity near-completely depletes eosinophils.
- Dupilumab (anti-IL-4Rα). QUEST showed exacerbation reduction and FEV1 improvement scaling with baseline eosinophils and FeNO;8 VENTURE showed OCS-sparing independent of baseline eosinophils.13 Uniquely also licensed across CRSwNP, atopic dermatitis and COPD.
- Tezepelumab (anti-TSLP). NAVIGATOR showed ~56% exacerbation reduction across the whole population, including benefit in patients with eosinophils <300 cells/µL — the first biologic to act upstream of the T2 split.9 SOURCE (OCS-sparing) missed its overall primary endpoint but showed benefit in the high-eosinophil subgroup.18
7 · A practical selection framework
Selection integrates biomarkers, comorbidities, dosing preference and funding. A pragmatic approach:
| Clinical situation | Reasonable first-line consideration(s) |
|---|---|
| Allergic, IgE in range, perennial sensitisation, lower eosinophils | Omalizumab (or tezepelumab) |
| Eosinophilic (eos ≥300), not OCS-dependent | Mepolizumab / benralizumab (or dupilumab if FeNO high / comorbid CRSwNP, AD) |
| OCS-dependent, eosinophilic | Benralizumab or dupilumab (largest OCS-sparing data); mepolizumab |
| Comorbid CRSwNP or atopic dermatitis | Dupilumab (single agent covers both) |
| Low/indeterminate T2 biomarkers, or biomarker variability on OCS | Tezepelumab (no eosinophil threshold) |
| EGPA | Mepolizumab (licensed) / benralizumab |
Blood eosinophils are suppressed by concurrent OCS — interpret biomarkers in that light and, where safe, before/along dose reduction. There are no adequately powered head-to-head RCTs between agents; selection rests on indirect comparison, biomarker fit and comorbidity. Assess response at ~4 months (exacerbations, OCS dose, symptom control, FEV1) and consider switching within or across class in partial/non-responders.3,19
8 · Extension into COPD — the newest frontier
The T2 paradigm has now crossed into COPD. In BOREAS and NOTUS, dupilumab in patients with COPD, chronic bronchitis and blood eosinophils ≥300 cells/µL (on triple inhaled therapy) reduced annual moderate-to-severe exacerbations by ~30% and improved lung function and symptoms20,21 — leading to the first biologic approval in COPD. This reframes eosinophilic COPD as another treatable T2 endotype and further erodes the old one-size reliever-plus-steroid model. Physiotherapists will increasingly meet COPD patients on a biologic in whom exacerbation frequency has dropped but exertional limitation and deconditioning persist.
9 · Safety across the class
- Injection-site reactions and nasopharyngitis are the commonest events; most agents are well tolerated long-term.
- Hypersensitivity/anaphylaxis: rare; a boxed warning applies to omalizumab (observe after early doses); reslizumab (IV) carries a small anaphylaxis risk.
- Dupilumab: conjunctivitis (notably in atopic dermatitis), transient blood eosinophilia early (rarely hypereosinophilic complications — check pre-treatment count), and injection-site reactions.
- Helminth infection: eosinophils contribute to anti-parasite defence — treat pre-existing helminth infection before anti-IL-5/5R therapy.
- Malignancy/immunogenicity: long-term registry data are reassuring; anti-drug antibodies are uncommon and rarely clinically significant.
- Pregnancy: data are accumulating (largest for omalizumab); decisions are individualised with specialist input.
10 · Response, super-responders and stopping
Roughly a third of treated patients are "super-responders" (exacerbation-free, off OCS, marked symptom/function gain); most others achieve meaningful partial benefit.3 Predictors of response include higher baseline eosinophils and FeNO, adult-onset disease, nasal polyps and clear T2 signal. The question of de-escalation or stopping is less settled: observational and early trial data (e.g. COMET for mepolizumab) suggest a proportion relapse after withdrawal, so continuation at the effective interval is the default in responders, with stopping reserved for shared-decision cases and close monitoring.22
11 · Implications for physiotherapy & allied health
- Unmasking of dysfunctional breathing. As eosinophilic inflammation is controlled, breathing-pattern disorder and vocal-cord dysfunction become the residual driver of "breathlessness" in a meaningful subgroup — a core physiotherapy target (breathing retraining, Papworth/Buteyko-style techniques within evidence limits).
- Deconditioning and the stable window. Reduced exacerbation frequency opens a durable window to deliver graded aerobic and resistance training and pulmonary rehabilitation — historically avoided during unstable disease.
- Airway clearance remains indicated with coexisting bronchiectasis or mucus hypersecretion; biologics do not replace it.
- Adherence and technique verification. Confirming inhaler technique and adherence is a prerequisite to biologic eligibility and an ongoing allied-health contribution — poor technique should never be "treated" with escalation to a biologic.1
- Comorbidity and OCS legacy. Patients tapering long-term OCS carry steroid-related sequelae (myopathy, osteoporosis, fragility) directly relevant to safe exercise prescription and falls risk.
The most important unanswered question is not whether biologics work — it is how to convert biologically controlled disease into restored function and fitness. There is a clear, under-researched role for structured rehabilitation in the newly stabilised severe-asthma and eosinophilic-COPD patient, directly analogous to the muscle-preservation opportunity in GLP-1-treated weight loss.
12 · Principal evidence gaps
- No adequately powered head-to-head RCTs between biologics; comparative effectiveness rests on indirect comparison and registries.19
- Optimal duration and safe withdrawal criteria are undefined; relapse rates after stopping are incompletely characterised.22
- Biomarkers predict response imperfectly; there is no validated tool to select between T2 agents for an individual.
- Effect on airway remodelling and long-term lung-function trajectory is not established.
- No RCT tests whether structured rehabilitation alters functional outcomes in the biologic-stabilised patient — the key allied-health question.
Selected trials: DREAM,15 MENSA,6 SIRIUS,11 SIROCCO,7 CALIMA,17 ZONDA,12 QUEST,8 VENTURE,13 NAVIGATOR,9 SOURCE,18 INNOVATE,5 MIRRA,16 BOREAS,20 NOTUS.21 Australian PBS/TGA status changes frequently and should be verified directly.
References & evidence base
- Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention: 2026 update. 2026. Available from: ginasthma.org.
- McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care Med 2019;199(4):433–445.
- Agache I, Song Y, Rocha C, et al. Efficacy and safety of treatment with biologicals for severe asthma: a systematic review for the EAACI guidelines. Allergy 2020;75(5):1023–1042.
- Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2026.
- Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma (INNOVATE). Allergy 2005;60(3):309–316.
- Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma (MENSA). N Engl J Med 2014;371(13):1198–1207.
- FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for severe asthma (SIROCCO). Lancet 2016;388(10056):2128–2141.
- Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma (QUEST). N Engl J Med 2018;378(26):2486–2496.
- Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma (NAVIGATOR). N Engl J Med 2021;384(19):1800–1809.
- Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy 2018;11:193–204.
- Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma (SIRIUS). N Engl J Med 2014;371(13):1189–1197.
- Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma (ZONDA). N Engl J Med 2017;376(25):2448–2458.
- Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma (VENTURE). N Engl J Med 2018;378(26):2475–2485.
- Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy (EXTRA). Ann Intern Med 2011;154(9):573–582.
- Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380(9842):651–659.
- Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis (MIRRA). N Engl J Med 2017;376(20):1921–1932.
- Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma (CALIMA). Lancet 2016;388(10056):2115–2127.
- Wechsler ME, Menzies-Gow A, Brightling CE, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with severe asthma (SOURCE). Lancet Respir Med 2022;10(7):650–660.
- Menzella F, Bertolini F, Biava M, et al. Severe refractory asthma: current treatment options and ongoing research. Drugs Context 2018;7:212561.
- Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts (BOREAS). N Engl J Med 2023;389(3):205–214.
- Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation (NOTUS). N Engl J Med 2024;390(24):2274–2283.
- Moore WC, Kornmann O, Humbert M, et al. Stopping versus continuing long-term mepolizumab in severe eosinophilic asthma (COMET). Eur Respir J 2022;59(1):2100396.
References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines and trial evidence in this field are living documents — verify against the latest version and current Australian PBS/TGA status before clinical use. For drug-specific detail, including full product information, consult MedsInfo.
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