Comparative Safety Profile of the Fixed-Dose Combination Corticosteroid and Long-acting β2-Agonist Fluticasone Propionate/Formoterol Fumarate: A 36-Month Longitudinal Cohort Study in UK Primary Care

Drugs. 2020 Jan;80(1):47-60. doi: 10.1007/s40265-019-01224-8.

Abstract

Objective: The inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fluticasone propionate/formoterol fumarate (FP/FORM; Flutiform®) has been available as fixed-dose combination (FDC) therapy for asthma patients aged ≥ 12 years in the UK since 2012. This post-authorisation safety study examined adverse outcomes and prescribing practices for FP/FORM and other FDC ICS/LABA therapies in a real-life clinical setting over 36 months.

Methods: Historical, longitudinal cohort database study using UK primary care data from the Clinical Practice Research Datalink (CPRD) database, for patients initiated on or switched to an FDC ICS/LABA (ENCePP study number: EUPAS12330). The main cohort was adults aged ≥ 18 years with asthma. The primary outcome was incidence of new adverse outcomes after initiation of ICS/LABA; hazard ratios (HRs) and 95% confidence intervals were estimated for FP/FORM versus other FDC ICS/LABAs using Cox regression models.

Results: A total of 241,007 patients with an FDC ICS/LABA prescription were identified. In the adult asthma cohort (N = 41,609), the incidence rate of new adverse outcomes [in 100 patient-years (py)] was significantly lower for FP/FORM (24.75) versus fluticasone/salmeterol metered-dose inhaler [8.86; HR 1.14 (1.04, 1.25)], fluticasone/salmeterol dry powder inhaler [31.19; HR 1.18 (1.08, 1.29)], budesonide/formoterol [25.16; HR: 1.13 (1.03, 1.25)] and beclometasone/formoterol [25.47; HR 1.14 (1.04, 1.25)]. The overall prescribing rate was lower for FP/FORM (13.85 per 1000/py) than licensed FDC ICS/LABA comparators (20.30-28.13 per 1000/py). Of those prescribed FP/FORM, 80.8% were adults with asthma and < 7% were prescribed FP/FORM "off-label".

Conclusions: The results suggest that FP/FORM was associated with an overall lower adverse outcome rate than the licensed comparators.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / adverse effects
  • Asthma / drug therapy*
  • Beclomethasone / administration & dosage
  • Beclomethasone / adverse effects
  • Budesonide, Formoterol Fumarate Drug Combination / administration & dosage
  • Budesonide, Formoterol Fumarate Drug Combination / adverse effects
  • Cohort Studies
  • Drug Combinations
  • Female
  • Fluticasone / administration & dosage*
  • Fluticasone / adverse effects
  • Fluticasone-Salmeterol Drug Combination / administration & dosage
  • Fluticasone-Salmeterol Drug Combination / adverse effects
  • Formoterol Fumarate / administration & dosage*
  • Formoterol Fumarate / adverse effects
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Primary Health Care
  • Retrospective Studies
  • United Kingdom

Substances

  • Anti-Asthmatic Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • fluticasone-formoterol
  • Fluticasone
  • Beclomethasone
  • Formoterol Fumarate