Generic Fluticasone–Salmeterol Inhaler for COPD Matches Branded Product

A generic fluticasone-salmeterol (Wixela Inhub) maintenance inhaler was clinically equivalent to name-brand Advair Diskus for chronic obstructive pulmonary disease (COPD), a propensity score-matched cohort study found.

With approximately 3 months of routine use, the generic form of the inhaled corticosteroid and long-acting beta-agonist (ICS-LABA) inhaler was shown to carry a similar incidence of first moderate-to-severe COPD exacerbation (HR 0.97, 95% CI 0.90-1.04) or pneumonia hospitalizations (HR 0.99, 95% CI 0.86-1.15), reported William Feldman, MD, DPhil, MPH, of Brigham and Women's Hospital in Boston, and colleagues.

"Evidence supporting the effectiveness and safety of generic ICS-LABAs can help promote less expensive options for patients with COPD who require an inhaled corticosteroid as part of their regimen," the authors wrote in the Annals of Internal Medicine.

The generic fluticasone-salmeterol inhaler was FDA approved in 2019, the first on the market for COPD and asthma. Approval had been based solely on spirometry data from an asthma population, however, so the present study now lends confidence to the COPD indication.

"I think this study should help assuage any concerns that generic inhalers may not function as well as brand-name versions," Feldman told MedPage Today in an email.

"The FDA applies rigorous standards when approving complex generic products like inhalers. So, I am not surprised that the generic version of fluticasone-salmeterol proved to be as safe and effective as the brand-name version in COPD. That being said, I think these sorts of post-approval studies are important, because the FDA can only require so much in the way of pre-approval testing," he said.

ICS-LABAs such as fluticasone-salmeterol are likely to continue playing an important role in the management of COPD, even though the most recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend triple therapy -- with an additional long-acting muscarinic antagonist (LAMA) -- for those needing an ICS.

Feldman's group noted that triple therapy inhalers are expensive, with patent extending into the 2030s, and there is no generic on the U.S. market. "The ease of using a single inhaler may boost adherence, but excess out-of-pocket spending could counteract and even outweigh these benefits in some patients," the wrote.

"Now that there are generic ICS-LABAs and generic LAMAs (the first was approved earlier in 2023), patients and payers may find that triple therapy via generic ICS-LABAs and generic LAMAs is cheaper," Feldman said.

For the present study, his group probed the Optum's deidentified Clinformatics Data Mart and identified 27,305 COPD patients with a new prescription for the brand-name inhaler and 18,604 newly prescribed the generic inhaler from January 2018 to June 2021. All were insured adults over 40 years of age.

Based on factors such as baseline lung disease and demographic variables, propensity matching led to 10,012 matched pairs. Of those patients, over two-thirds were white, about 14% were Black, and 11% were Hispanic. The average patient age was 72 years and women accounted for about 60% of the population. Nearly 30% of patients received their index prescriptions during the COVID-19 pandemic.

Median follow-up was 88 days for the primary effectiveness endpoint. Patients had been followed for up to 1 year after cohort entry or until index therapy was discontinued or changed, among other events.

Crude incidence of first moderate-to-severe COPD exacerbation was 435 and 410 events per 1,000 person-years for the branded and generic groups, respectively, the bulk of which were moderate cases (393 and 367 per 1,000 person-years). Definitions involved prednisone for 5 to 14 days for moderate exacerbations and a COPD-related hospitalization for severe cases, as defined by ICD-9 codes.

As for safety, incidence of first pneumonia hospitalization reached 104 events per 1,000 person-years in the brand-name group and 100 per 1,000 person-years in the generic group.

Limitations to the observational study include the potential for residual confounding and the short follow-up times. Investigators cautioned that they also had to assume that inhalers were used correctly by study participants, and they did not assess safety risks outside pneumonia.

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