Updated October 2025

Severe Asthma Care

Asthma Management: Biologics and Step‑Up Therapy

Biologic therapies targeting type 2 inflammation reduce severe exacerbations, oral corticosteroid (OCS) exposure, and improve control in appropriately selected patients with severe asthma. Step‑up therapy should follow a control‑based, phenotype‑directed pathway with timely reassessment, de‑escalation when controlled, and OCS‑sparing strategies.

Clinical question

In adults with uncontrolled asthma, how should clinicians apply step‑up therapy and when should biologics be initiated, selected, and monitored for efficacy?

asthmabiologicsstep-up therapytype 2 inflammationOCS-sparing

Key points

Confirm severity and optimize fundamentals

Before stepping up, verify diagnosis, inhaler technique, adherence, and comorbidities. Step up only after addressing these modifiable factors, consistent with control‑based frameworks. Escalations should be reassessed within 3–10 days for acute step‑ups and within 4–12 weeks for controller adjustments ^[7], ^[8].

When to start biologics

Consider for severe asthma uncontrolled on high‑dose ICS/LABA ± LAMA with frequent exacerbations, OCS dependence, and evidence of type‑2 inflammation (eosinophils, FeNO, atopy). All major biologics reduce exacerbations, with OCS‑sparing benefits in OCS‑dependent disease ^[1], ^[4], ^[9], ^[3].

Assess early response and switch if needed

Evaluate response by 3–4 months: exacerbations, OCS dose, ACT/ACQ, FEV1, biomarkers. Switching between biologics can recapture control; real‑world data support effectiveness of switching after nonresponse ^[10].

Plan step‑down

After sustained control (≥3 months), step down toward the lowest effective regimen while monitoring for relapse; follow control‑based step‑down yardsticks ^[8].

Aim for OCS avoidance

Use biologics to prevent OCS initiation and reduce OCS‑related adverse outcomes; observational data show fewer new OCS‑related harms after biologic initiation ^[6].

Evidence highlights

≈30–60% relative reduction in severe exacerbations (strong evidence) ^[1], ^[2], ^[3]

Exacerbation reduction with anti–T2 biologics

Biologics significantly reduce maintenance OCS exposure (network meta-analysis) ^[4]

OCS dose reduction

Biologic initiation lowers exacerbations, healthcare use, and OCS exposure ^[5], ^[6]

Real‑world outcomes

Care Pathway

Structured Step‑Up to Biologics

A pragmatic, phenotype‑directed sequence from optimization to targeted biologic selection and monitoring.

Validate uncontrolled status and optimize basics

Confirm asthma diagnosis and severity; check inhaler technique, adherence, triggers, and comorbidities. Apply control‑based adjustment: impairment and risk guide therapy intensity ^[8], ^[11].

Short‑term step‑up for loss of control

For acute worsening, temporarily increase controller intensity; terminate step‑up after 3–10 days once control is regained ^[7].

Escalate controller therapy

Ensure high‑dose ICS/LABA, consider LAMA and mitigation of exposures. Reassess within 4–12 weeks for control and risk metrics ^[8], ^[11].

Biologic candidacy assessment

Identify type‑2 phenotype: eosinophils, FeNO, atopy/IgE. Indications include ≥2 severe exacerbations/year, OCS dependence, or persistent symptoms despite optimized high‑dose therapy ^[1], ^[9].

Select a biologic aligned to endotype and goals

Anti‑IgE (omalizumab) for allergic asthma; anti‑IL‑5/IL‑5R (mepolizumab, reslizumab, benralizumab) for eosinophilic disease; anti‑IL‑4Rα (dupilumab) for T2‑high with elevated FeNO/eosinophils or atopic multimorbidity. All reduce exacerbations; OCS‑sparing effects are demonstrated across agents ^[1], ^[4], ^[9], ^[3].

Monitor response and adapt

At 3–4 months, judge response using exacerbation rate, OCS dose, ACT/ACQ, FEV1, FeNO/eosinophils, and QoL. If partial/nonresponse, consider switching biologics; real‑world evidence supports switching efficacy ^[10], ^[5].

Step‑down and long‑term safety

If stable for ≥3–6 months, cautiously reduce background ICS/LABA or dosing intervals while monitoring. Biologics are generally well‑tolerated with acceptable safety profiles and lower OCS‑related adverse outcomes after initiation ^[6], ^[3].

Practical Tools

Selecting and Using Biologics

Key considerations for matching biologics to patient phenotypes and objectives.

Type‑2 markers to check

Blood eosinophils (e.g., ≥150–300/µL supportive)

FeNO (elevated supports IL‑4/IL‑13 pathway)

Total/Specific IgE and perennial allergen sensitization

Sputum eosinophils where available

Biologics and core effects

Omalizumab (anti‑IgE): ↓ exacerbations in allergic asthma; benefits higher with atopy/elevated IgE ^[1], ^[9]

Mepolizumab/Reslizumab (anti‑IL‑5): ↓ exacerbations, OCS‑sparing in eosinophilic asthma ^[1], ^[4], ^[9]

Benralizumab (anti‑IL‑5Rα): robust eosinophil depletion, fewer exacerbations, OCS‑sparing ^[1], ^[4], ^[9]

Dupilumab (anti‑IL‑4Rα): ↓ exacerbations, improved control, OCS‑sparing; benefits with high FeNO/eosinophils ^[1], ^[4], ^[9]

Measured outcomes and targets

Exacerbations: aim ≥50% reduction

OCS dose: minimize or discontinue if possible ^[4], ^[6]

ACT/ACQ: clinically meaningful improvement

FEV1: objective improvement from baseline

Healthcare utilization: ER/ hospitalization reductions ^[5]

Timing and reassessment

Acute step‑up: stop at 3–10 days once control achieved ^[7]

Biologic response check: 12–16 weeks; continue, optimize, or switch ^[10]

Sustained control: consider step‑down after ≥3 months ^[8]

Safety and risk mitigation

Anaphylaxis risk with some agents; observe per label

Helminth infections: treat prior to IL‑4Rα blockade

Herpes/eye complaints with dupilumab: monitor

Vaccinations: non‑live vaccines generally acceptable

Aim to prevent OCS toxicity; biologics linked to fewer new OCS‑related adverse outcomes ^[6]

Evidence strength at a glance

Systematic reviews/NMA: consistent exacerbation reduction across biologics ^[1], ^[2], ^[3]

OCS‑sparing NMA: clinically meaningful reductions in OCS dose ^[4]

Real‑world cohorts: confirm effectiveness, healthcare gains, and support switching ^[10], ^[5]

Guideline principle: control‑based stepping up/down ^[8], ^[11]

Data Highlights

Quantitative Effects

Synthesized effect sizes useful for clinical discussions.

Exacerbation risk

Across biologics, relative reductions ≈30–60% in severe exacerbations versus standard care (systematic reviews) ^[1], ^[2], ^[3]

OCS‑sparing

Network meta‑analysis shows significant OCS dose reduction and increased probability of OCS discontinuation with anti‑IL‑5/5R and anti‑IL‑4Rα agents ^[4]

Healthcare utilization and safety

Real‑world initiation of biologics associated with fewer exacerbations and hospital/ED visits and reduced OCS exposure ^[5]

Biologic use linked to lower incidence of new OCS‑related adverse outcomes in severe asthma ^[6]

References

Source material

Primary literature that informs this article.