When to Hold Triple Therapy in COPD
Triple therapy with medications like Trimbow (beclomethasone/formoterol/glycopyrronium) should be held or adjusted when patients develop pneumonia, have significant drug interactions, or when the risk of adverse effects outweighs the benefits in patients at low risk of exacerbations.
Indications for Holding or Adjusting Triple Therapy
1. Development of Pneumonia
- Triple therapy containing inhaled corticosteroids (ICS) significantly increases the risk of pneumonia, especially in patients with severe COPD 1
- The number needed to harm is 33 patients treated for 1 year to cause one pneumonia 1, 2
- Hold triple therapy and consider switching to dual bronchodilator therapy (LAMA/LABA) if pneumonia develops
2. Patients at Low Risk of Exacerbations
- Triple therapy provides minimal additional benefit for patients at low risk of exacerbations 1
- Consider stepping down to LAMA/LABA dual therapy in:
- Patients with no history of exacerbations in the past year
- Patients with blood eosinophil counts <100 cells/μL 2
- Patients experiencing significant ICS-related adverse effects
3. Adverse Effects Requiring Temporary or Permanent Discontinuation
- Oral candidiasis or persistent hoarseness/dysphonia unresponsive to proper inhaler technique and mouth rinsing
- Significant bruising or skin thinning
- Adrenal suppression symptoms
- Worsening glaucoma or cataracts
- Significant bone mineral density loss
4. Drug Interactions
- Hold triple therapy when using medications with significant QT interval prolongation if adding macrolide therapy 1
- Consider drug interactions when using medications that may interact with LAMA component (anticholinergics)
Special Considerations
Blood Eosinophil Levels
- Patients with low blood eosinophil counts (<100 cells/μL) receive minimal benefit from the ICS component 2
- Consider holding or removing the ICS component in these patients if they develop pneumonia or other ICS-related adverse effects
Stepping Down Approach
- Do not abruptly discontinue triple therapy in patients at high risk of exacerbations 1
- If stepping down is necessary:
- Consider gradual reduction of ICS dose before complete withdrawal
- Monitor closely for worsening symptoms or exacerbations
- Be especially cautious in patients with blood eosinophil counts ≥300 cells/μL 1
Monitoring After Adjustment
- Reassess patients 4-8 weeks after any therapy change 2
- Monitor for:
- Changes in symptom burden (using CAT score or mMRC dyspnea scale)
- Lung function changes (spirometry)
- Signs of exacerbation
Algorithm for Decision-Making
Assess exacerbation risk:
- High risk: ≥2 moderate exacerbations or ≥1 severe exacerbation (hospitalization) in past year
- Low risk: 0-1 moderate exacerbations, no hospitalizations in past year
Check blood eosinophil count:
- <100 cells/μL: Consider holding ICS component if adverse effects occur
- ≥300 cells/μL: Maintain triple therapy if possible
Evaluate for pneumonia or other adverse effects:
- If pneumonia: Hold triple therapy until resolution, then reassess need
- If other significant adverse effects: Consider stepping down to LAMA/LABA
For patients at low exacerbation risk with adverse effects:
- Step down to LAMA/LABA dual therapy
- Monitor closely for 4-8 weeks
For patients at high exacerbation risk with adverse effects:
- Consider temporary hold of triple therapy until adverse effect resolves
- Resume at lower ICS dose if possible
- Consider alternative approaches (macrolide, roflumilast, or N-acetylcysteine) if unable to tolerate triple therapy 1
Remember that the benefits of triple therapy in preventing exacerbations (NNT=4 to prevent one moderate-severe exacerbation) must be balanced against the risks of pneumonia (NNH=33) 1, 2. This risk-benefit assessment should guide decisions about when to hold or adjust triple therapy.