COPD Therapeutic Update

Transcription

1 COPD Therapeutic Update The first ever NT patient.. Hubertus PA Jersmann MBBS, MD, PhD, FRACP, FThorSoc, AMA(M) Professor, School of Medicine, University of Adelaide Respiratory and Sleep Physician, Royal Adelaide Hospital Visiting Specialist, Alice Springs Hospital Talks: AstraZeneca Menarini Boehringer Ingelheim Mundipharma Novartis PulmonX COI Advisory Boards: GSK, AstraZeneca, Mundipharma, Menarini, Novartis Clinical Trials: Novartis, GSK, AstraZeneca, Boehringer Ingelheim No honorarium for this presentation Take Home Messages COPD is common & Early Diagnosis is pivotal for successful intervention Treatable Traits is a novel approach to the patient with airways disease Targeted use of inhaled steroids, NOT FOR EVERY PATIENT Novel therapies are being developed but most not deployable yet Humanomics is the key to successful management of COPD Definition of COPD COPD affects over 2 million Australians Of these, 1.2 million have COPD severe enough to impact their daily lives Preventable, treatable disease Characterised by airflow limitation, which is not fully reversible Usually progressive Diagnosis based on: - a history of smoking, or exposure to other noxious agents - FEV 1 /FVC <0.7 post-bronchodilator on spirometry Among Australians aged 40 years, the prevalence of COPD is 18.6% COPD IS OFTEN MISSED 50% of all symptomatic COPD remains undiagnosed COPD IS OFTEN MISDIAGNOSED Commonly misdiagnosed as asthma, and vice versa. The COPD-X Plan, Henderson J et al. Aust Fam Physician 2012; 41: 841. Abramson et al, The COPD-X Plan: Australian and New Zealand Guidelines for the management of Chronic Obstructive Pulmonary Disease Mapel D et al. Int Journal of COPD 2011: 6; Price D et al. Prim Care Respir J 2011; 20: Soriano JB et al. Lancet 2009; 374: Walters JA et al. Prim Care Respir J 2011; 20: Tinkelman DG et al. J Asthma 2006; 43: Jones RC et al. Respir Res 2008; 9: 62. 1

2 FLOW (L/s) FLOW (L/s) Normal Treatable traits: a new approach to management of airway disease Obstructive Defect Normal TIME (s) TIME (s) Smoking? Mucus +++ Exacerbations ++ Eosinophils, BD reversibility Smoking? Mucus +++ Exacerbations ++ Eosinophils Hypoxaemia/hypercapnia Smoking? Smoking? Modified from: Pavord ID, et al. After asthma: redefining airways diseases. Lancet Jan27; 391(10118): Alvar Agusti, Elisabeth Bel, Claus Vogelmeier, Guy Brusselle, Stephen Holgate, Marc Humbert, Peter Gibson, Jørgen Vestbo, Richard Beasley, Ian Pavord Eur RespirJ : OPTIMISE FUNCTION Reduce risk COPD management - Smoking cessation, influenza and pneumococcal vaccination Optimise function - Encourage physical activity, review nutrition, provide education, develop management plan, initiate regular review Consider comorbidities - Especially osteoporosis, coronary disease, lung cancer, anxiety, depression Refer to pulmonary rehabilitation consider psychosocial needs, action plan COPD-X Concise Guide for Primary Care, 2016., Frith P. A manual for pulmonary rehabilitation in Australia, Respir Crit Care Med 2013; Spruit M, et al. Am J Vaccination More than once? Pertussis? Reflux Air pollution (Diesel, wild fires) Indoor Temperatures (21 0 C optimal) COPD management, continued. Tseng C-M, Chen Y-T, Ou S-M, Hsiao Y-H, Li S-Y, Wang S-J, et al. (2013) The Effect of Cold Temperature on Increased Exacerbation of Chronic Obstructive Pulmonary Disease: A Nationwide Study. PLoS ONE 8(3): e Meredith C. McCormack et al. Ann Am Thorac Soc Dec; 13(12): Liesl M. Osman et al. Home warmth and health status of COPD patients. European Journal of Public Health, Volume 18, Issue 4, 1 August 2008, Pages Anxiety and depression are common in COPD The downward spiral of symptom-induced inactivity Decramer M. Eur Resp Rev 2006; 15: This where Pulmonary Rehab works!! 2

3 Proportion surviving LAMA/LABA non-inferior to or better than LABA/ICS FLAME 3362 patients Brimica Genuair versus Salmeterol/Fluticasone AFFIRM 933 patients Wedzicha JA et al. N Engl J Med 2016; 374: Vogelmeier C et al. Eur Respir J 2016;48(4): Role of ICS: Peripheral eosinophilia? WISDOM study of withdrawal of ICS from triple therapy The data suggest that eosinophil counts greater than 300 cells per μl might identify a need for ICS COPD-X prospective validation is required before routine clinical recommendations can be made. WISDOM was a 12-month, randomised, parallel-group trial in which 2485 patients with COPD and a history of exacerbations received 18 μg tiotropium, 100 μg salmeterol, and 1000 μg fluticasone propionate daily for 6 weeks and were then randomly assigned to receive either continued or reduced ICS over 12 weeks. A post-hoc analysis after complete ICS withdrawal (months 3 12) compared the rate of exacerbations and time to exacerbation outcomes on the basis of blood eosinophil subgroups of increasing cut-off levels. Watz H et al. Lancet Respir Med 2016; 4: The COPD-X PLan, Role of ICS: Peripheral eosinophilia? Long-term triple therapy de-escalation to indacaterol/ glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET) The SUNSET trial evaluated the efficacy of de-escalation from long-term triple therapy to indacaterol/glycopyrronium only in non-frequently exacerbating patients with COPD patients using long-term triple therapy were randomised to indacaterol/glycopyrronium 110/50μg once daily or continuation of triple therapy (tiotropium 18μg once daily plus salmeterol/fluticasone propionate 50/500μg twice daily) for 26 weeks in a triple-dummy design. ICS withdrawal led to a reduction in trough FEV 1 of 26mL but the annualised rate of moderate or severe COPD exacerbations did not differ between treatments. Patients with 300 blood eosinophils/μl at baseline had greater lung function loss and higher exacerbation risk. Chapman K et al. Am J Respir Crit Care Med 2018;198(3): COPD exacerbations Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory-changing, and often deadly manifestations of a chronic disease. GPs are at the forefront of managing exacerbations Mild/moderate cases can be managed as outpatients Survival after hospitalisation for first COPD exacerbation Kaplan-Meier survival curve of 73,106 patients from the time of first hospitalisation for a COPD exacerbation 17-year follow-up period Time after first severe exacerbation (years) Criner GJ et al. Chest 2015; 147: Yawn BP. Journal of Primary Care and Community Health 2013; 4: Suissa S et al. Thorax 2012; 67:

4 Concept & History of Lung Volume reduction How to check for Collateral ventilation Surgical morbidity is significant and non-pulmonary comorbidities may preclude surgery SA data SA data Female, 72y Ht cm Wt 57.7 kg BMI 24.8 kg/m2 Other techniques SA data Coils 4

5 Other developments / the future Coils Novel Lung volume reduction therapies in development - STEAM Broncus (Uptake Medical) - Foam/glue Aeriseal (PulmonX) Targeted Lung denervation Cryospray Therapy Tissue regeneration If the patient has less than 2 years to live and is not too old and not too unwell: Lung Transplantation The latest The latest Macrolides (low dose azithromycin) Eosinophils as biomarker Humanomics Humanomics 5

6 Exacerbations/patient Take Home Messages The MIRROR Study COPD is common & Early Diagnosis is pivotal for successful intervention Treatable Traits is a novel approach to the patient with airways disease Targeted use of inhaled steroids, NOT FOR EVERY PATIENT Novel therapies are being developed but most not deployable yet Humanomics is the key to successful management of COPD QUESTIONS? Supplementary slides Budesonide/Formoterol plus tiotropium reduces severe exacerbations vs tiotropium alone 0.4 Symbicort 400/12 μg bd + tiotropium 18 μg od Placebo + tiotropium 18 μg od Days since randomisation 12-week randomised, double-blind, parallel-group, multicentre study of 660 patients with COPD eligible for ICS/LABA combination therapy with an FEV 1 <50% predicted and a history of exacerbations requiring systemic steroids and/or oral antibiotics Primary outcome (change in predose FEV 1 from randomisation to 12 weeks) was met. Severe exacerbations = worsening of COPD requiring systemic corticosteroids [oral or parenteral] and/or hospitalisation/emergency room visits Adapted from Welte T et al. Am J Respir Crit Care Med 2009; 180: