Efficacy and safety comparison: Fluticasone furoate and fluticasone propionate, after step down from fluticasone furoate/vilanterol in Japanese patients with well-controlled asthma, a randomized trial.
For patients with well-controlled asthma, 'step down' of therapy is recommended. We evaluated Japanese patients switching from inhaled corticosteroid (ICS)/long-acting beta2-agonists (LABA; equivalent to fluticasone propionate [FP]/salmeterol [SAL] 250/50 μg twice daily [BD]) to fluticasone furoate (FF)/vilanterol (VI) 100/25 μg, then stepping down to ICS alone.



This phase III trial had two treatment periods (P): P1, patients with well-controlled asthma on FP/SAL 250/50 μg BD equivalent stepped across to once daily (OD) FF/VI 100/25 μg (open-label, eight weeks); P2, patients remaining 'well controlled' after P1 stepped down to FF 100 μg OD/FP 100 μg BD/FP 250 μg BD (randomized 1:1:1, double-blind, 12 weeks). Co-primary P2 endpoints: percentage of patients with well-controlled asthma; time to withdrawal due to poorly controlled asthma requiring step-up therapy. Adverse events (AEs) were monitored.



At the end of P1 (n = 430), 373 (90.5%; 95% confidence interval 87.29-93.18) patients' asthma remained well controlled with FF/VI; in P2 (n = 371), control was maintained in 89.5% (FF 100 μg)/79.5% (FP 100 μg)/83.8% (FP 250 μg) of patients. In P2, 4.9-7.3% of patients were withdrawn due to worsening asthma (time-to-withdrawal cumulative incidence curves were comparable). AEs were reported by 37% of patients during P1; and by 36% (FF 100 μg)/48% (FP 100 μg)/49% (FP 250 μg) of patients in P2.



For patients with well-controlled asthma on mid dose ICS/LABA (equivalent to FP/SAL 250/50 μg BD), control can be maintained when they are stepped across to FF/VI 100/25 μg OD. FF 100 μg OD is an effective step-down therapy from FF/VI 100/25 μg OD with similar efficacy to FP 100 μg BD and FP 250 μg BD.
Department of Clinical Research Centers, International University of Health and Welfare/Sanno Hospital, 10-16, Akasaka 8-chome, Minato-ku, Tokyo, 107-0052, Japan.
Mitsuru
M
Adachi
Quantitative Sciences Division, GSK, London, TW8 9GS, UK.
Caroline
C
Goldfrad
Respiratory Medicine Discovery and Development, GSK, London, TW8 9GS, UK.
Loretta
L
Jacques
Development & Medical Affairs Medicines Development Respiratory TA Office, GSK, 6-15, Sendagaya 4-chome, Shibuya-ku, Tokyo, 151-8566, Japan. Electronic address: yoshie.2.nishimura@gsk.com.
Yoshie
Y
Nishimura
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000627:therapeutic use; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage* / Q000494:pharmacology; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage* / Q000627:therapeutic use; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D015995:Prevalence; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; C000611924:fluticasone furoate-vilanterol trifenatate; D000068298:Fluticasone; C523187:fluticasone furoate
Asthma; Inhaled corticosteroid; Long-acting beta(2)-agonist; Well-controlled asthma; ‘Step across’ of asthma therapy; ‘Step down’ of asthma therapy