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Randomized Controlled Trial
. 2023 Aug;176(8):1047-1056.
doi: 10.7326/M23-0615. Epub 2023 Aug 8.

Comparative Effectiveness and Safety of Generic Versus Brand-Name Fluticasone-Salmeterol to Treat Chronic Obstructive Pulmonary Disease

William B Feldman  1 , Aaron S Kesselheim  2 , Jerry Avorn  2 , Massimiliano Russo  3 , Shirley V Wang  3
Affiliations
Randomized Controlled Trial

Comparative Effectiveness and Safety of Generic Versus Brand-Name Fluticasone-Salmeterol to Treat Chronic Obstructive Pulmonary Disease

William B Feldman et al. Ann Intern Med. 2023 Aug.

Abstract

Background: In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone-salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications.

Objective: To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone-salmeterol among patients with COPD treated in routine care.

Design: A 1:1 propensity score-matched cohort study.

Setting: A large, longitudinal health care database.

Patients: Adults older than 40 years with a diagnosis of COPD.

Measurements: Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry.

Results: Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]).

Limitations: Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded.

Conclusion: Use of generic and brand-name fluticasone-salmeterol was associated with similar outcomes among patients with COPD treated in routine practice.

Primary funding source: National Heart, Lung, and Blood Institute.

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Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0615.

Figures

Figure 1:
Figure 1:. Cohort composition
Figure 2:
Figure 2:. Sensitivity analyses for first moderate or severe COPD exacerbation
CI: confidence interval. *This refers to the primary analysis, which permitted 60 days between fills before censoring a patient for non-persistence. This figure shows the hazard ratios and 95% confidence intervals of first moderate or severe COPD exacerbation in new users of Wixela Inhub vs. Advair Diskus across a range of prespecified sensitivity analyses. The two treatments groups had similar incidence rates for the outcome.
Figure 3:
Figure 3:. Subgroup analyses for first moderate or severe COPD exacerbation
CI: confidence interval. This figure shows the hazard ratios and 95% confidence intervals of first moderate or severe COPD exacerbation in new users of Wixela Inhub vs. Advair Diskus across a range of prespecified subgroup analyses. The two treatments groups had similar incidence rates across subgroups.
See this image and copyright information in PMC

Comment in

References

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