What are the criteria for using Roflumilast (Daxas) in patients with Chronic Obstructive Pulmonary Disease (COPD)?

Criteria for Use of Roflumilast in COPD

Roflumilast is indicated for patients with severe COPD associated with chronic bronchitis and a history of exacerbations, not as first-line therapy, not based solely on symptom scores, and not as a rescue medication or for acute exacerbations. 1

Patient Selection Criteria

• Roflumilast should be used in patients with:

  • Severe or very severe airflow obstruction (post-bronchodilator FEV1/FVC <0.70 and FEV1 <50% predicted) 2
  • Chronic bronchitis phenotype 2, 1
  • History of exacerbations despite optimal inhaled therapy 2

• Roflumilast is specifically indicated to reduce the risk of COPD exacerbations in this patient population 1

Timing in Treatment Algorithm

• Roflumilast is NOT used as first-line therapy after COPD diagnosis 1
• Roflumilast is added to existing therapy when patients continue to have exacerbations despite optimal inhaled treatments 2
• The 2023 Canadian Thoracic Society guideline suggests roflumilast for patients with chronic bronchitis phenotype at high risk of exacerbations who have moderate to high symptom burden (CAT ≥10, mMRC ≥2) and impaired lung function (FEV1 <80% predicted) 2

Important Distinctions

• Roflumilast is NOT used acutely as a rescue medication 1
• Roflumilast is NOT used for treatment of acute exacerbations of COPD 1
• Roflumilast is NOT a bronchodilator and should not be used for relief of acute bronchospasm 1
• Roflumilast is NOT prescribed based solely on high CAT and mMRC scores 2

Clinical Benefits

• Roflumilast reduces the number of moderate or severe exacerbations per patient-year (rate ratio 0.85,95% CI 0.78-0.91) 2
• Roflumilast decreases the proportion of patients who develop exacerbations (21.4% versus 25.2%; risk ratio 0.85,95% CI 0.78-0.94) 2
• Roflumilast prolongs time to next exacerbation (hazard ratio 0.88,95% CI 0.81-0.96) 2
• Roflumilast modestly improves lung function with increases in FEV1 (mean difference +56.29 mL) and FVC (mean difference +98.45 mL) 2

Combination with Other Therapies

• Roflumilast can be used concomitantly with long-acting bronchodilators 3, 4
• Some studies show benefit when roflumilast is added to triple therapy in patients who continue to have exacerbations 5

Common Side Effects and Precautions

• Patients receiving roflumilast are more likely to experience:

  • Diarrhea (9.7% versus 2.7%; risk ratio 3.96) 2
  • Nausea (4.8% versus 1.4%; risk ratio 3.54) 2
  • Weight loss (8.4% versus 2.3%; risk ratio 3.94) 2
  • Psychiatric disorders including anxiety and depression (7.1% versus 3.5%; risk ratio 2.13) 2
  • Sleep disturbance/insomnia (3.1% versus 1.1%; risk ratio 2.88) 2

• Higher discontinuation rates due to adverse effects occur with roflumilast compared to placebo (14.9% versus 9.0%; risk ratio 1.80) 2

• In real-world studies, side effects and discontinuation rates may be even higher (69.1% and 49.1% respectively) 5

Dosing Considerations

• Roflumilast 250 mcg is a starting dose for the first 4 weeks of treatment only 1
• The therapeutic dose is 500 mcg once daily 1, 6

In conclusion, roflumilast is a targeted therapy for a specific COPD population with severe disease, chronic bronchitis, and exacerbations despite optimal inhaled therapy. It is not appropriate as first-line therapy, as a rescue medication, or for acute exacerbations.