Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Abstract

Introduction In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination. Methods Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Database sm were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013–March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history. Results The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history. Conclusions In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history. Trial Registration ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019). Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01646-5.

Prescription Patterns of New Use of Fixed-Dose Combination Inhalers in Patients with Chronic Obstructive Pulmonary Disease: Long-Acting β2 Agonists Plus Long-Acting Muscarinic Antagonists versus Long-Acting β2 Agonists Plus Inhaled Corticosteroids

“…Cumulative literature pointed out that LABA/LAMA FDC may be more efficacious while having less adverse reactions such as lower respiratory tract infections than LABA/ICS FDC. [21][22][23][24] Our results, to some extent, reflect that FDC prescription patterns in daily practice may adhere to the recommendations of available evidence.…”

“…Patient Characteristics for LABA/LAMA FDC or LABA/ICS FDC Use Some comparative effectiveness or safety studies of LABA/LAMA and LABA/ICS combination therapies (either FDC or free combination forms) noticed that baseline patient characteristics differed between treatment groups. 23,24,28,29 For example, in one study using a US commercial claims database, Samp et al showed that patients who started LABA/ LAMA combination therapy were older, more likely to be male, had more comorbidities, including cardiovascular diseases, any cancer, lung cancer, mental health disorder, and pneumonia, and had more frequent resource utilization due to COPD compared to patients who started LABA/ICS combination therapy. 29 Similar to Samp et al's results, our study also found that LABA/LAMA FDC initiators were generally more vulnerable than LABA/ICS FDC initiators.…”

Chronic Obstructive Pulmonary Disease Exacerbations and Pneumonia Hospitalizations Among New Users of Combination Maintenance Inhalers

“…This may have biased findings, since patients prescribed multiple inhalers are more likely to be nonadherent to treatment and require urgent care visits, emergency department visits, and hospitalizations compared with patients receiving the same therapy via combination inhalers . A third study, which found a benefit for LAMA-LABA therapy via a single inhaler, analyzed only 1 LAMA-LABA (tiotropium-olodaterol) and included patients using other LAMA-LABAs during the washout period while excluding those who used ICS-LABAs, which may have biased findings toward tiotropium-olodaterol. All 3 studies were limited by small sample sizes in the exposure group.…”

Dual bronchodilation for the treatment of COPD: From bench to bedside

“…A Japanese real‐world study suggested that, compared with new users of tiotropium, new users of tiotropium/olodaterol had a numerically lower probability of escalating to triple therapy or experiencing moderate or severe COPD exacerbations 94 . Furthermore, data from the US HealthCore Integrated Research Database revealed that both individually and in combination, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia and escalation to triple therapy in patients with COPD compared to ICS/LABA 95 ; the combined risk was reduced regardless of baseline eosinophils or exacerbation history.…”

“…Furthermore, data from the US HealthCore Integrated Research Database revealed that both individually and in combination, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia and escalation to triple therapy in patients with COPD compared to ICS/LABA95 ; the combined risk was reduced regardless of baseline eosinophils or exacerbation history.8 | A NEW PARADIGM IN COPD THERAPY: USING DUAL BRONCHODILATION AS INITIAL MAINTENANCE TREATMENTOptimising bronchodilation requires concurrent modification (blockade on one side and stimulation on the other) of both the parasympathetic and sympathetic arms of the autonomic nervous system 12. …”