Why are alternative therapies needed for asthma?

Why Alternative Therapies Are Needed for Asthma

Alternative asthma therapies exist because patients vary in their response to preferred treatments, some cannot tolerate inhaled corticosteroids due to side effects or contraindications, and individual patient factors like adherence, ability to use inhalers, and willingness to use certain medications necessitate different therapeutic options. 1

Core Reasons for Alternative Therapy Options

Patient-Specific Treatment Limitations

• Inhaled corticosteroids (ICS), while the most consistently effective anti-inflammatory therapy, are not suitable for all patients due to side effects such as increased intraocular pressure, which necessitates non-steroid alternatives like leukotriene receptor antagonists (LTRAs). 2

• Individual sensitivity and responsiveness to asthma medications varies significantly among patients, making it essential to have multiple therapeutic options when preferred treatments fail to achieve adequate control. 1

• Patient willingness and ability to use specific medications differs—for example, LTRAs offer advantages of oral once-daily dosing with high compliance rates compared to inhaled medications that require proper technique. 1, 2

Safety Concerns with Preferred Agents

• Long-acting beta agonists (LABAs) carry safety warnings including increased risk of severe exacerbations and deaths when used as monotherapy, requiring them to be combined with ICS and limiting their use in certain clinical scenarios. 1

• High-dose systemic corticosteroids pose significant toxicity risks including glucose metabolism abnormalities, weight gain, hypertension, peptic ulcer, and aseptic necrosis, making corticosteroid-sparing alternatives necessary for some patients. 1, 3

• Theophylline requires careful serum concentration monitoring and has numerous drug interactions and conditions that alter its clearance (CHF, liver disease, fever, smoking status), making it a less desirable but sometimes necessary alternative. 1, 4

Clinical Scenarios Requiring Alternatives

For mild persistent asthma (Step 2), when patients are unable or unwilling to use low-dose ICS, alternative options include:

• Leukotriene receptor antagonists (montelukast or zafirlukast) 1
• Cromolyn sodium or nedocromil (mast cell stabilizers) 1
• Theophylline (requires monitoring) 1

For moderate persistent asthma (Steps 3-4), when the preferred combination of ICS plus LABA is not suitable, alternatives include:

• ICS plus LTRA 1
• ICS plus theophylline 1
• ICS plus zileuton (requires liver function monitoring) 1

Heterogeneity of Asthma Pathophysiology

• Asthma demonstrates significant phenotypic and endotypic heterogeneity, with different inflammatory pathways predominating in different patients, meaning no single medication effectively targets all disease mechanisms. 3, 5

• Some patients have relatively treatment-resistant asthma or specific phenotypes (such as severe allergic asthma) that require targeted biologics like omalizumab rather than standard controller therapy. 1, 5

Important Clinical Considerations

Effectiveness Hierarchy

• LTRAs are generally less effective than ICS for controlling asthma but provide a viable non-steroid alternative when ICS cannot be used. 2

• The combination of ICS plus LABA demonstrates superior efficacy compared to ICS plus LTRA, with stronger evidence supporting this as the preferred step-up approach. 1, 6

Common Pitfalls to Avoid

• Never use LABAs as monotherapy for long-term asthma control due to safety concerns; they must always be combined with ICS. 1

• If an alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up to the next therapy level. 1

• Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the requirement for liver function monitoring. 1

Monitoring Requirements

• Patients on alternative therapies require close follow-up at 2-4 week intervals initially to assess response, with ongoing monitoring at 1-6 month intervals depending on control level. 2

• All patients need access to short-acting beta-agonists (SABAs) for rescue use regardless of which long-term controller therapy is selected. 2

• Theophylline use mandates serum concentration monitoring due to narrow therapeutic index and multiple factors affecting clearance. 1, 4