Dual therapy improves not only lung function but also quality of life in COPD patients

Recommendations for initiating COPD pharmacotherapy

GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommends stepwise pharmacotherapy for COPD, starting with monotherapy with LAMA or LABA and can be escalated to a dual combination of LAMA + LABA in subsequent steps. American recommendations suggest this dual combination as the first step in treatment for patients with dyspnea and exercise intolerance. To aid physicians in deciding whether to prescribe monotherapy or combination therapy, a pooled analysis of clinical trial results OTEMTO 1, 2 and TONADO 1, 2 was conducted, evaluating the addition of LABA to existing LAMA monotherapy in patients with moderate to very severe COPD.

Analyzed data

The analysis included 299 patients diagnosed with moderate to severe COPD (OTEMTO studies) or moderate to very severe COPD (TONADO studies) who were on LAMA monotherapy. Patients were aged ≥ 40 years, smokers or former smokers (> 10 pack-years), with FEV₁ < 80% and an FEV₁/FVC ratio < 70%. The presence of symptoms was not a requirement.

Patients were randomized into two groups: 151 continued with LAMA monotherapy (5 µg tiotropium), 148 received a fixed LAMA/LABA combination (5/5 µg tiotropium/olodaterol).

The analysis focused on changes in the parameter of forced expiratory volume in 1 second (FEV₁), quality of life according to the SGRQ (St. George's Respiratory Questionnaire) and dyspnea according to the TDI (Transition Dyspnea Index) scores after 12 weeks of treatment compared to baseline.

Results after 12 weeks of treatment

The trough FEV₁ value increased on average by 0.159 ± 0.015 L in the LAMA/LABA combination group and by 0.085 ± 0.015 L in the tiotropium monotherapy group. The adjusted mean difference between the combination and tiotropium was 0.074 ± 0.021 L (95% confidence interval [CI] 0.033–0.115; p = 0.0004).

The average improvement in quality of life (decrease in SGRQ score) with combination therapy was by 5.981 ± 0.88 points more compared to baseline, with tiotropium monotherapy it was by 3.306 ± 0.88 points more vs. baseline. The adjusted mean difference between LAMA/LABA combination and LAMA alone was 2.675 ± 1.21 points (95% CI –5.060 to –0.291; p = 0.0280).

The TDI parameter was monitored in 283 patients. In probands treated with the tiotropium/olodaterol combination, there was an average reduction in dyspnea (increase in TDI score) by 1.911 ± 0.21 points, and in patients treated with tiotropium alone by 0.763 ± 0.21 points. The adjusted mean difference between the combination and LAMA alone was 1.148 ± 0.30 points (95% CI 0.56–1.73; p= 0.0001).

Clinically relevant improvement in at least one examined category was demonstrated by 128 (87.7%) patients on LAMA/LABA and 111 (74.5%) patients treated with LAMA alone.

The analysis found similar safety profiles of the products in both branches, indicating the safety of transitioning from monotherapy to dual therapy. Most adverse events were mild to moderate in severity.

Conclusion

In patients with COPD treated with LAMA monotherapy, escalation to a fixed LAMA/LABA combination led to statistically and clinically significant improvements in lung function, quality of life, and reduction of dyspnea. The results support the early initiation of dual bronchodilation therapy to optimize the treatment of patients with moderate to very severe COPD.

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Source: Buhl R., Singh D., Hoz A. et al. Benefits of tiotropium/olodaterol compared with tiotropium in patients with COPD receiving only LAMA at baseline: pooled analysis of the TONADO and OTEMTO studies. Adv Ther 2020 Aug; 37: 3485–3499, doi: 10.1007/s12325-020-01373-3.