10/3/2017 Topics to be covered Pharmacotherapy for chronic treatment Pharmacotherapy for COPD Dr. W C Yu 3rd September 2017 Commonly used drugs Guidelines for their use Inhaled corticosteroids (ICS) in COPD Preventing acute exacerbations and hospitalization Goals for chronic treatment of COPD ABCD assessment tool Improve well-being Reduce dyspnoea Improve exercise tolerance Improve quality of life Reduce risks Prevent exacerbations Reduce disease progression Reduce mortality Group A All Group A patient should be offered bronchodilator treatment based on its effect on breathlessness. This can be either a short- or longacting bronchodilator This should be continued if symptomatic benefit is documented 1
Oral bronchodilators Oral bronchodilators Theophyllines (Nuelin SR), Bricanyl Durules Twice daily formulation Less effective than inhaled bronchodilators Side effects hand tremor, palpitations Anorexia (theophyllines) If a patient strongly request oral bronchodilator.... He/she is almost certainly not using their inhalers properly, or at all Short acting inhaled bronchodilator LABA Twice daily formulation: Salmeterol Formoterol Once daily formulation (ultra-laba) Indacaterol (Onbrez Breezhaler) Olodacterol (Striverdi Respimat) Vilanterol salbutamol ipratropium LAMA Group B Initial therapy should consist of a long-acting inhaled bronchodilator (LABA or LAMA) glycopyrronium There is no evidence to recommend one class of LABD over another for initial relief of symptoms tiotropium aclidinium (twice daily) umeclidinium For patients with persistent breathlessness on monotherapy the use of two bronchodilators is recommended 2
Group B (conti.) For patients with severe breathlessness initial therapy with two bronchodilators may be considered If the addition of a second bronchodilator does not improve symptoms, GOLD suggest step back to single bronchodilator Address comorbidities Group C Initial therapy should consist of a LAMA as clinical trials has shown that it is superior to LABA in preventing exacerbations Patients with persistent exacerbations may benefit from adding a second LABD (preferred) or using LABA/ICS Inhaled corticosteroids (ICS) LABA+ICS beclomethasone budesonide fluticasone Salmeterol / fluticasone (Seretide) Formoterol / budesonide (Vannair) fluticasone / vilanterol (Relvar) LABA+LAMA Group D indacaterol / glycopyrronium (Ultibro) formoterol / aclidinium (Duaklir) vilanterol / fluticasone (Anoro) olodacterol / tiotropium (Spiolto) Starting with LAMA+LABA is recommended, though LAMA alone or LABA/ICS can be considered LABA/ICS may be preferred for those with features of asthma (ACOS) Note that group D patients are at higher risk for developing pneumonia when receiving treatment with ICS 3
Group D (conti.) Group D (conti.) In patients who develop further exacerbations on LABA/LAMA, suggest two alternative pathways: Escalate to LABA/LAMA/ICS Switch to LABA/ICS (less preferred unless ACOS) In patients treated with LABA/LAMA/ICS still have exacerbations, consider: Add roflumilast, if the patient have FEV1 <50% predicted and chronic bronchitis Add a macrolide. Azithromycin is preferred. Mindful for development of resistant organisms Stopping ICS Inhaled Corticosteroids (ICS) in COPD ICS Use and Pneumonia Risk in COPD Regular treatment with ICS alone does not modify long term decline in FEV1 nor mortality Cochrane Database Syst Rev 2012;29[2]:129-43 NEJM 2007;35(8)6:775-89 Lancet 2016;387:1817-26 ICS/LABA is more effective than either component alone: in improving lung function In improving health status in reducing exacerbations Cochrane Database Syst Rev 2012;9[9]:CD006829;2013;8[8]:CD006826 Low dose = FLU <500 µg Moderate = FLU 500 <1,000 µg High dose = FLU 1,000 µg Yawn BP et al. Int J COPD 2013; 8:295 304 ICS better start in those who likely benefit High risk for exacerbations 2 or more exacerbations in the previous 12 months FEV1 less than 50% predicted Likely have COPD-asthma overlap History of childhood asthma or atopy Onset of respiratory disease prior to the age of 40 years Cumulative smoking history < 20 pack years FEV1 bronchodilator response > 15% or > 400ml With eosinophilia Peripheral blood eosinophilia >= 2% Sputum eosinophilia 2,485 subjects with history of exacerbations and on ICS+ LABA+ LAMA, randomised into 2 arms continue ICS withdraw ICS over 12-week period FU for one year Primary end point: time to first moderate or severe AECOPD: no difference between the two groups No difference in dyspnoea and QoL scores More fall of FEV1 in the withdrawal group 4
Acute exacerbation of COPD Cause accelerated lung function decline Donaldson GC, et al. Thorax 2002;57:847-52 Associated with worse quality of life Seemungal TAR, et al. Am J Respir Crit Care Med 2012;157:1418-22 Spencer S, et al. Thorax 2003;58:589-93 Associated with greater mortality than acute myocardial infarction (30-day mortality 26% vs. 7.8%) Berkius J, et al. Acta Anaesthesiol Scand 2008;52:759-65 Yeh RW, et al. N Engl J Med 2010;362:2155-65 Occupy a lot of medical beds Measures to prevent AECOPD Appropriate use of drugs (groups C, D) Smoking cessation Influenza and pneumococcal vaccinations Exercise training Patient education on self management Home care visits by HCW, hot line, tele-health hospital-at-home stock of antibiotics and oral steroids (e kit supervised by CNS) CNS-based home care programme RCT involving 180 patients discharged after AECOPD Comprehensive, individualized care plan involving education, exercise training, regularly FU by respiratory specialist, vs. usual care At 12 months, the intervention group: less readmission (adjusted RR=0.668) shorter hospital stay, less dyspnea, better QoL Retrospective study August 2010 December 2012, PMH Patients who were hospitalized >= 2 times for AECOPD in the last 12 months and referred for CNS care recruited Total 124 patients (mean age 75 years): 67 patients received CNS care (7 home visits + 2 home visits in 15 weeks) 57 patients refused CNS care All CNS received a certificate course on COPD home care Ko FWS, et al. Thorax 2017;72:122-128 CNS-based home care programme E kit Admission frequency 12m before 12m after change Total bed days occupied 12m before 12m after change CNS group n=67 4.16 3.01-27.75% 30.37 32.05 +5.5% No CNS group n=57 p value 3.70 4.40 +18.8% <0.01 26.95 37.85 +40.46% <0.01 Augmentin 375mg tds x 1 week plus prednisolone 30mg daily x 1 week To be taken at home when there are symptoms of AECOPD Directed by CNS May be able to avoid AED attendance / admission unpublished data 5
Key points Pharmacotherapy for chronic COPD management is symptom- and admission- driven, not directly related to lung function. Choice of drugs should be according to ABCD grouping No particular preference for drug choice within-group Preventing AECOPD is a key objective for COPD management Multi-disciplinary input is important 6