Effectiveness and tolerability of formoterol plus glycopyrronium combination in patients with chronic obstructive pulmonary disease: FINE registry

Authors

  • Bharat Gopal Department of Respiratory and Sleep Medicine, Maharaja Agrasen Hospital, India National Chest Centre, New Delhi, India
  • K. S. Satish Chest and Maternity Centre, Fortis Hospital and Vikram Hospital, Bengaluru, Karnataka, India
  • Samir Garde Interventional Pulmonology and Critical Care, Wockhardt Hospital, Dhanwantari Hospital and Global Hospital, Mumbai, Maharashtra, India
  • Niranjan Kumar Sit Department of Pulmonary Medicine, Rampurhat Government Medical College and Hospital, Burdwan, West Bengal, India
  • Dipali Kamdar Jaydeep Hospital, Ahmedabad, Gujarat, India
  • Sameer Muchhala Medical Services, Zydus Healthcare Ltd., Mumbai, Maharashtra, India
  • Ashwin V. Jadhav Medical Services, Zydus Healthcare Ltd., Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2349-3933.ijam20204064

Keywords:

Glycopyrronium, Formoterol fumarate, LAMA, LABA, COPD

Abstract

Background: Long-term therapy for chronic obstructive pulmonary disease (COPD) is progressing fast. Dual bronchodilation with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) fixed dose combinations (FDC) have been available over the past few years. To evaluate the real-world tolerability and effectiveness of formoterol plus glycopyrronium FDC inhaler, a post-marketing surveillance study was conducted in Indian population.

Methods: This was an open-label, observational registry in which COPD patients, who were prescribed forglyn (a brand of FDC of glycopyrronium 25 mcg and formoterol fumarate dihydrate 6 mcg dry powder inhalation). The effectiveness, safety and tolerability of this LAMA/LABA combination were evaluated for 4, 8 and 12 weeks. The safety and tolerability was assessed based on the incidence of adverse events (AEs). Effectiveness was evaluated based on change in total symptom score from baseline to end of 12 weeks. The forced expiratory volume in 1 second (FEV1) was performed at baseline and end of 12 weeks.

Results: Total COPD patients enrolled were 605, of which 78.5% were males and 21.5% were females. Patients showing improvement of symptoms at week 4 were 587 (97.02%).

Overall, at the end of 8 week and 12 week 98.34 % and 99.49% patients showed improvement in the total symptoms respectively. About 0.49% did not show any improvement. AEs were reported in 64 (10.64%) patients with no serious AEs. Mean FEV1 of 476 patients before treatment was 1.53±0.68 L at baseline which changed to 1.85±4.74 L at the end of 12 weeks, with was statistically significant (p<0.05).

Conclusions: In real-life clinical practice in India, formoterol and glycopyrronium FDC dry powder inhaler was well tolerated in COPD patients, and can be regarded as an effective option for maintenance treatment.

Author Biographies

Bharat Gopal, Department of Respiratory and Sleep Medicine, Maharaja Agrasen Hospital, India National Chest Centre, New Delhi, India

Senior Consultant & Head,Maharaja Agrasen Hospital, New Delhi

And Director, National Chest Centre, New Delhi

K. S. Satish, Chest and Maternity Centre, Fortis Hospital and Vikram Hospital, Bengaluru, Karnataka, India

Senior pulmonologist

Samir Garde, Interventional Pulmonology and Critical Care, Wockhardt Hospital, Dhanwantari Hospital and Global Hospital, Mumbai, Maharashtra, India

Consultant respiratory disease, Interventional pulmonology and critical care

Niranjan Kumar Sit, Department of Pulmonary Medicine, Rampurhat Government Medical College and Hospital, Burdwan, West Bengal, India

Professor and HOD (Head of department) pulmonary medicine.

Dipali Kamdar, Jaydeep Hospital, Ahmedabad, Gujarat, India

Consultant pediatric pulmonologist,bronchoscopist and sleep specialist

Sameer Muchhala, Medical Services, Zydus Healthcare Ltd., Mumbai, Maharashtra, India

General Manager, Medical services

Ashwin V. Jadhav, Medical Services, Zydus Healthcare Ltd., Mumbai, Maharashtra, India

Senior ManagerMedical services

References

Yum HK, Kim HR, Chang YS, Shin KC, Kim S, Oh YM. Safety and Effectiveness of Indacaterol in Chronic Obstructive Pulmonary Disease Patients in South Korea. Tuberc Respir Dis (Seoul). 2017;80(1):52-9.

Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respiratory Critical Care Med. 2007;176(6):532-55.

Organization WH OW. Chronic respiratory diseases. Burden of COPD. 2020. Available at: https://wwwwhoint/respiratory/copd/burden/en/. Accessed on: 24 February 2020.

Jindal SK, Aggarwal A, Gupta D, Agarwal R, Kumar R, Kaur T, et al. Indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults (INSEARCH). Int J Tuberculosis Lung Dis. 2012;16(9):1270-7.

Sinha B, V, Singla R, Chowdhury R. An epidemiological profile of chronic obstructive pulmonary disease: A community-based study in Delhi. J Postgraduate Med. 2017;63(1):29-35.

Rogliani P, Calzetta L, Braido F, Cazzola M, Clini E, Pelaia G, et al. LABA/LAMA fixed-dose combinations in patients with COPD: a systematic review. Int J Chron Obstruct Pulmon Dis. 2018;13:3115-30.

Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017;195(5):557-82.

Calzetta L, Matera MG, Cazzola M. Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy. Eur J Pharmacol. 2015;761:168-73.

Rodrigo GJ, Price D, Anzueto A, Singh D, Altman P, Bader G, et al. LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis. International journal of chronic obstructive pulmonary disease. 2017;12:907.

Cazzola M, Calzetta L, Ora J, Puxeddu E, Rogliani P, Matera MG. Searching for the synergistic effect between aclidinium and formoterol: from bench to bedside. Respiratory medicine. 2015;109(10):1305-11.

Soriano JB, Maier WC, Egger P, Visick G, Thakrar B, Sykes J, et al. Recent trends in physician diagnosed COPD in women and men in the UK. Thorax. 2000;55(9):789-94.

Feenstra TL, van Genugten ML, Hoogenveen RT, Wouters EF, Rutten-van Molken MP. The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands. Am J Respir Crit Care Med. 2001;164(4):590-6.

Kim EJ, Yoon SJ, Kim YE, Go DS, Jung Y. Effects of Aging and Smoking Duration on Cigarette Smoke-Induced COPD Severity. J Korean Med Sci. 2019;34(1):90.

Wilson DO, Rogers RM, Wright EC, Anthonisen NR. Body weight in chronic obstructive pulmonary disease. The National Institutes of Health Intermittent Positive-Pressure Breathing Trial. Am Rev Respir Dis. 1989;139(6):1435-8.

Sinha B, Singla R, Chowdhury R. An epidemiological profile of chronic obstructive pulmonary disease: A community-based study in Delhi. J Postgrad Med. 2017;63(1):29-35.

Orozco-Levi M, Garcia-Aymerich J, Villar J, Ramirez-Sarmiento A, Anto J, Gea J. Wood smoke exposure and risk of chronic obstructive pulmonary disease. Eur Respiratory J. 2006;27(3):542-6.

Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. New Engl J Med. 2014;371(14):1285-94.

Ejiofor S, Turner AM. Pharmacotherapies for COPD. Clin Med Insights Circ Respir Pulm Med. 2013;7:17-34.

Martinez FJ, Rabe KF, Ferguson GT, Fabbri LM, Rennard S, Feldman GJ, et al. Efficacy and safety of glycopyrrolate/formoterol metered dose inhaler formulated using co-suspension delivery technology in patients with COPD. Chest. 2017;151(2):340-57.

Al-Salama ZT, Frampton JE. Glycopyrronium/Formoterol: A Review in COPD. Drugs. 2019;79(13):1455-66.

Fakih F, Spangenthal S, Sigal B, Darken P, Maes A, Siddiqui S, et al. Randomized study of the effects of Aerochamber Plus(R) Flow-Vu(R) on the efficacy, pharmacokinetics and safety of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler in patients with chronic obstructive pulmonary disease. Respir Med. 2018;138:74-80.

Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2014(3).

Kunz LI, Postma DS, Klooster K, Lapperre TS, Vonk JM, Sont JK, et al. Relapse in FEV1 decline after steroid withdrawal in COPD. Chest. 2015;148(2):389-96.

Dhungana S, Criner GJ. Spotlight on glycopyrronium/formoterol fumarate inhalation aerosol in the management of COPD: design, development, and place in therapy. Int J Chron Obstruct Pulmon Dis. 2017;12:2307-12.

Singh D, Worsley S, Zhu C-Q, Hardaker L, Church A. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulmonary Med. 2015;15(1):91.

Farne HA, Cates CJ. Long‐acting beta 2‐agonist in addition to tiotropium versus either tiotropium or long‐acting beta 2‐agonist alone for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2015(10).

Hanania NA, Tashkin DP, Kerwin EM, Donohue JF, Denenberg M, O'Donnell DE, et al. Long-term safety and efficacy of glycopyrrolate/formoterol metered dose inhaler using novel Co-Suspension Delivery Technology in patients with chronic obstructive pulmonary disease. Respir Med. 2017;126:105-15.

Hanania NA, Tashkin DP, Kerwin E, Donohue J, Denenberg M, O’Donnell D, et al. Safety and efficacy of a novel LAMA/LABA co-suspension technology glycopyrrolate/formoterol fixed-dose combination delivered by MDI: results of a one-year extension study in patients with COPD (PINNACLE-3). D36 COPD: LABA, LAMA, ICS, AND COMBINATIONS: American Thoracic Society. 2016;6791.

Hanrahan JP, Grogan DR, Baumgartner RA, Wilson A, Cheng H, Zimetbaum PJ, et al. Arrhythmias in patients with chronic obstructive pulmonary disease (COPD): occurrence frequency and the effect of treatment with the inhaled long-acting beta2-agonists arformoterol and salmeterol. Medicine. 2008;87(6):319-28.

Campbell SC, Criner GJ, Levine BE, Simon SJ, Smith JS, Orevillo CJ, et al. Cardiac safety of formoterol 12 μg twice daily in patients with chronic obstructive pulmonary disease. Pulmonary pharmacology Therapeutics. 2007;20(5):571-9.

Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369(16):1491-501.

Van de Maele B, Fabbri LM, Martin C, Horton R, Dolker M, Overend T. Cardiovascular safety of QVA149, a combination of Indacaterol and NVA237, in COPD patients. COPD. 2010;7(6):418-27.

Vogelmeier C, Verkindre C, Cheung D, Galdiz JB, Guclu SZ, Spangenthal S, et al. Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients. Pulm Pharmacol Ther. 2010;23(5):438-44.

Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018;13:3971-81.

Downloads

Published

2020-09-22

Issue

Section

Original Research Articles