Olodaterol Hydrochloride/Tiotropium Bromide

The Global Initiative for Chronic Obstructive Lung Disease (GOLD 2023) no longer recommends a long-acting β₂-agonist (LABA) plus inhaled corticosteroid (ICS) combination for the treatment of chronic obstructive pulmonary disease (COPD). In patients treated with LABA/ICS, who continue to experience symptoms without frequent or severe exacerbations, GOLD now recommends switching to long-acting muscarinic antagonist (LAMA)/LABA instead of escalating to triple therapy (TT; LAMA/LABA/ICS), which previously was also a recommended option. EVELUT^®, a real-life, observational study, compared these two treatment strategies in terms of symptom relief and health status improvement.

Patients with symptomatic COPD at low exacerbation risk (GOLD B) were switched, at their physicians' discretion, from LABA/ICS to either fixed-dose LAMA/LABA (tiotropium/olodaterol, Respimat^® [Tio/Olo]) or fixed or free TT. Primary endpoints were change in modified Medical Research Council (mMRC) and COPD Assessment Test™ (CAT™) scores after 12 weeks.

The safety set contained 463 patients (Tio/Olo, n = 329; TT, n = 134). In a propensity score-matched set (Tio/Olo, n = 121; TT, n = 121), improvement in mMRC score was similar in patients on Tio/Olo (-0.23; 95% confidence interval [CI] -0.11, -0.36) and TT (-0.25; 95% CI -0.13, -0.38). Improvement in total CAT score was slightly larger in patients on Tio/Olo (-3.45; 95% CI -2.45, -4.45) versus TT (-2.51; 95% CI -1.62, -3.40). In both groups, Physician's Global Evaluation scores increased, with 69-89% of patients satisfied with their treatment overall. Marginally more patients on Tio/Olo responded to treatment versus TT (Δ mMRC score ≥ 1; 25% vs. 22%; Δ CAT score ≥ 2, 68% vs. 56%).

In patients with symptomatic COPD at low exacerbation risk, treatment can be switched from LABA/ICS to LAMA/LABA without compromising clinical benefit, compared with escalating to LAMA/LABA/ICS. Switching from LABA/ICS to LAMA/LABA can provide symptom relief and improve health status without exposure to the risks associated with ICS.

ClinicalTrials.gov: NCT03954132.

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting β₂agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304). DISCLOSURES: The study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Dr Sethi has received honoraria/fees for consulting/speaking from Astra-Zeneca, BIPI, and GlaxoSmithKline. He has received consulting fees for serving on data safety monitoring boards from Nuvaira and Pulmotect. He has received consulting fees from Apellis and Aerogen. His institution has received research funds for his participation in clinical trials from Regeneron and AstraZeneca. Ms Palli was an employee of BIPI at the time the study was conducted. Drs Clark and Shaikh are employees of BIPI. Ms Buysman and Mr Sargent are employees and Dr Bengtson was an employee of Optum, which was contracted by BIPI to conduct this study. Dr Ferguson reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants from Novartis, Altavant, and Knopp; grants and personal fees from AstraZeneca, Verona, Theravance, Teva, and GlaxoSmithKline; and personal fees from Galderma, Orpheris, Dev.Pro, Syneos, and Ionis outside the submitted work. He was a paid consultant for BIPI for this study. The authors received no direct compensation related to the development of the manuscript. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.