What is the approach for step-up therapy in patients with uncontrolled asthma?

Step-Up Therapy for Uncontrolled Asthma

For patients with uncontrolled asthma, the preferred step-up approach is to first check adherence, inhaler technique, and environmental control, then advance therapy according to the stepwise approach, with adding a long-acting beta-agonist (LABA) to inhaled corticosteroids (ICS) being preferred over increasing ICS dose alone. 1

Assessment Before Step-Up

Before stepping up therapy, always evaluate:

• Medication adherence
• Inhaler technique
• Environmental triggers
• Comorbid conditions (especially allergic rhinitis, GERD, obesity)

Poor control indicators requiring step-up:

• Use of rescue inhaler >2 days/week
• Nighttime awakenings due to asthma
• Activity limitation due to symptoms
• ≥2 exacerbations requiring oral corticosteroids in the past year 1

Stepwise Approach to Step-Up Therapy

Step 1 to Step 2

• Current: As-needed SABA only
• Step-up to: Daily low-dose ICS plus as-needed SABA 1, 2

Step 2 to Step 3

• Current: Low-dose ICS
• Step-up options:
  • Preferred: Low-dose ICS plus LABA
  • Alternative: Medium-dose ICS or low-dose ICS plus leukotriene receptor antagonist (LTRA) 1

Step 3 to Step 4

• Current: Low-dose ICS plus LABA or medium-dose ICS
• Step-up to: Medium-dose ICS plus LABA 1, 2

Step 4 to Step 5

• Current: Medium-dose ICS plus LABA
• Step-up to: High-dose ICS plus LABA
• Consider: Adding tiotropium (especially for patients with exacerbations) 1, 3

Step 5 to Step 6

• Current: High-dose ICS plus LABA
• Step-up to: High-dose ICS plus LABA plus oral corticosteroids
• Consider: Biologics (omalizumab for allergic asthma) 1

Evidence for Step-Up Choices

When choosing between increasing ICS dose versus adding LABA:

• Adding LABA to ICS provides better symptom control and lung function improvement than increasing ICS dose 1
• However, increasing ICS dose may provide better protection against severe exacerbations and hospitalizations in some patients 4
• Add-on tiotropium has been shown to reduce exacerbation risk by 35% compared to increasing ICS+LABA dose in patients with uncontrolled asthma 3

Important Considerations

ICS Dosing

• 80-90% of maximum therapeutic benefit is achieved with standard doses (200-250 μg fluticasone propionate equivalent) 5
• High-dose ICS shows no additional clinical benefit in most efficacy parameters but increases risk of adverse effects 6

LABA Safety

• LABAs should never be used as monotherapy for asthma
• Always combine with appropriate ICS dose
• Monitor for cardiovascular side effects 1, 2

Monitoring Response

After step-up therapy:

• Reassess control in 1-3 months
• If well-controlled for ≥3 months, consider step-down
• If no improvement after 1-3 months, reconsider diagnosis or adjust therapy 1

Special Situations

Severe Exacerbations

• For patients with ≥2 exacerbations in the past year, consider them as having uncontrolled asthma regardless of symptom control
• Consider earlier specialist referral 1

When to Refer

Referral to an asthma specialist is recommended when:

• Step 4 care or higher is required
• Patient has had ≥2 bursts of oral corticosteroids in the past year
• Hospitalization for asthma has occurred
• Additional testing is indicated 1

Remember that the goal of step-up therapy is to achieve and maintain asthma control while minimizing medication side effects and the risk of exacerbations.