Dr Stephen Child. Chief Medical Officer Southern Cross Health Society Auckland

Transcription

1 Dr Stephen Child Chief Medical Officer Southern Cross Health Society Auckland 7:00-7:55 GlaxoSmithKline Breakfast Session - Hot Topics in Airways Disease: COPD and Asthma

2 Hot Topics in Airways Disease: Asthma and COPD Dr Stephen Child General Physician Auckland City Hospital TAPS 1852JS/18JUN/NZ/RESP/0011/18

3 Conflict of Interest Pharmaceutical sponsorship Procare, Homecare Medical Clinical Governance Medical Council elected member I have not received any payment from GSK to conduct this talk. I am not GSK employee and do not hold shares in GSK. Any opinion expressed during this presentation is my own opinion and may not be that of GSK.

4 Outline Code ) What s new in Obstruction? 2) Eosinophilic vs Non Eosinophilic 3) When inhaled steroids? 4).what should I do?

5 Showing the upper and lower airways (Last viewed: 7 June, 2010)

6 Normal Airflow VC Vol 75% FEV 1.0 1s Time 6s Dr Stephen Child s diagrammatic adaptation demonstrating normal airflow. (Dr Stephen Child, Auckland City Hospital, Auckland, NZ)

7 Obstructive Airflow FEV 1.0 < 0.70 VC FVC 40% 1s Dr Stephen Child s diagrammatic adaptation demonstrating obstructive airflow. (Dr Stephen Child, Auckland City Hospital, Auckland, NZ)

8 68 yo COPD presents with SOB and wheeze Which is NOT relevant to DDx? 1. Previous Builder 2. On Propanolol 3. Recent syncopal episode 4. BMI= Rheumatoid Arthritis Code

9 The 2017 GOLD strategy update: Definition of COPD GOLD Chronic Obstructive Pulmonary Disease (COPD), a common preventable and treatable disease, is characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. GOLD Chronic Obstructive Pulmonary Disease (COPD).. persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases Reference: 1. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD)

10 Gladysheva, MA. & Owens, B. (2010) Influencing the decline of lung function in COPD: use of pharmacotherapy. Int J Chron Obstruct Pulmon Dis, 2010:5, pg

11 COPD - Eclipse 38% - >40 ml/yr decline 31% ml/yr decline 23% decline/improve 8% - >21 - improve Hurst, J., et al. (2010) Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med, 363:

12 Overlap of obstructive airways disease Asthma (Reversible) Eosinophils ICS responsive Neutrophils ICS unresponsive COPD (Non-Reversible) Dr. Stephen Child s diagrammatic adaptation of the overlap between reversible and non-reversible airways disease (Dr. Stephen Child, Auckland City Hospital, Auckland, NZ)

13 58 yo smoker with SOB x 8 years, chronic cough but no hospitalisations/prednisone IF you confirmed COPD, would your prescription include inhaled corticosteroids? 1. Yes 2. No Code

14 ICS and Pneumonia (Samy Suissa) 1 n= ~163,000 COPD > 55 yrs NNH = (* note NNT exac = 14-44) ~20,000 CAP nested case controls Overall, HR = FP = Dose responsive - Beclo = Cessation = drop risk - Bud = 1.2 A review conducted by the European Medicines Agency confirmed the risk of pneumonia with inhaled corticosteroids in COPD patients, however they did not find any conclusive evidence of differences in this risk for different products 1. 1 Suissa, S., et al. (2013) Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax, 68:1029: Adapted from:

15 The 2017 GOLD strategy update: COPD diagnosis and assessment General principles Spirometrically confirmed diagnosis Assessment of airflow limitation Assessment of symptoms/risk of exacerbations Exacerbation History FEV 1 /FVC <0.7 FEV 1 (% predicted) GOLD 1 80% GOLD % 2 or 1 leading to hospitalisation 0 or 1 (not leading to hospitalisation) GOLD % GOLD 4 <30% CAT <10 mmrc 0 1 Symptoms CAT 10 mmrc Global Initiative for Chronic Obstructive Lung Disease, all rights reserved. Use is by express license from the owner. CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; FEV 1, forced expiratory volume in 1 second; FVC, forced vital capacity; mmrc, Modified Medical Research Council Reference: Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD)

16 The 2017 GOLD strategy update: Management of stable COPD Goals for management of stable COPD Relieve symptoms Improve exercise tolerance Improve health status REDUCE SYMPTOMS Prevent disease progression Prevent and treat exacerbations Reduce mortality REDUCE RISK Treatment goals in COPD remain the same 2017 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved. Use is by express license from the owner. Reference: Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD)

17 COPD Exacacerbations Dr. Cat Chang Waikato 1 N = 248 COPD exac prospective cohort Day 30 mort 8.8% (17% Trop) (28% BNP) Day 365 mort 17.7% (ECLIPSE 2 = 35 50% mortality 1 year post exac) 1 Adapted by Dr. Stephen Child from original work carried out by Dr. Cat Chang (Dr. Stephen Child, Auckland City Hospital, Auckland, NZ) 2 Hurst, J., et al. (2010) Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med, 363:

18 A summary of LAMA, LAMA/LABA and ICS/LABA funded for COPD treatment in NZ LAMA Seebri Breezhaler GLYCOPYRRONIUM 1 Incruse Ellipta UMECLIDINIUM 2 LAMA/LABA Ultibro SA Breezhaler GLYCOPYRRONIUM INDACATEROL 4 Anoro Ellipta UMECLIDINIUM/ VILANTEROL 5 SA ICS/LABA Seretide Accuhaler FLUTICASONE PROPIONATE/SAL 7 Breo Ellipta FLUTICASONE FUROATE/VILANTEROL 8 Spiriva Respimat and Handihaler TIOTROPIUM 3 SA Spiolto Respimat TIOTROPIUM/ OLODATEROL 6 SA Symbicort Turbuhaler BUDESONIDE/ EFORMOTEROL 9 No special authority for umeclidinium or glycopyrronium, Special Authority (SA) criteria applies for tiotropium (the prescriber must provide written endorsement that the patient has been diagnosed as having COPD using spirometry to access subsidy). Special authority (SA) criteria applies to LAMA/LABA therapies 10 ICS = inhaled corticosteroid; LABA = long acting beta2 agonist; LAMA = long acting muscarinic antagonist SAL = salmeterol Reference: 1. Seebri Breezhaler Data Sheet, NOV New Zealand, 2015; 2. Incruse Ellipta Data Sheet, GSK New Zealand, 2015; 3. Spiriva Data Sheet, BI New Zealand, 2015; 4. Ultibro Breezhaler Data Sheet, NOV New Zealand, 2015; 5. Anoro Ellipta Data Sheet, GSK New Zealand, 2015; 6. Spiolto Data Sheet, BI New Zealand, 2015; 7. Seretide Data Sheet, GSK New Zealand, 2015; 8. Breo Ellipta Data Sheet, GSK New Zealand, 2015; 9. Symbicort Turbuhaler Data Sheet, AZ New Zealand, 2015; 10. Pharmaceutical Schedule, PHARMAC, May 2017.

19 Short-acting bronchodilators Overview of inhalers available for COPD in NZ ICS/LABA LABA or LAMA LAMA/LABA Adapted from (accessed 20/03/2017) ICS = inhaled corticosteroid; LABA = long acting beta2 agonist; LAMA = long acting muscarinic antagonist

20 Which of the following does NOT match? 1. Zealandium = LAMA 2. Zealandol = LAMA 3. Zealandazone = ICS 4. Zealandronate = bisphosphonate 5. Zealandol = LABA Code

21 Changes for Management of Stable COPD: Summary of new pharmacologic treatment algorithms in 2017 GOLD Update LAMA/LABA LABA/ ICS C Consider rolumilast if FEV 1 <50% predicted and patient has chronic bronchitis Consider macrolide D Green arrow indicated preferred treatment pathway Further exacerbation(s) LAMA Continue, stop or try alternative class of bronchodilator evaluate effect A Further exacerbation(s) LAMA LAMA/LABA/ICS Further exacerbation(s) LAMA/LABA LAMA/LABA Persistent symptoms Persistent symptoms/further exacerbation(s) ICS/ LABA B Risk (Increasing Exacerbations) A bronchodilator A long-acting bronchodilator (LABA or LAMA) Increasing Symptoms Reference: Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) 2017.

22 Number of events The benefit-risk of ICS/LABA in COPD patients is favourable Pooled data from 2 replicate COPD exacerbation studies (n=1624) FF/VI 100/25 mcg OD VI 25 mcg OD Exacerbations events Days Pneumonias 30 events Reference: Crim C et al. Annals ATS 2015;12:

23 Use of blood eosinophil count as a biomarker of ICS response could further improve risk-benefit ratio Annual exacerbation rate (patients/yr) Annual exacerbation rate by blood eosinophil count 1, % reduction P< % reduction P=NS 37% reduction P< All comers Blood eos count <2% Blood eos count >/=2% Vilanterol (22 mcg) Fluticasone furoate/vilanterol Post hoc analysis of pooled data from two replicate, double-blind, parallel-group, one-year studies comparing Fluticasone Furoate to Vilanterol 25 mcg in COPD patients with FEV1 <70% predicted and a documented history of >1 moderate /severe disease exacerbations in the preceding year. The 2 studies randomized 1622 & 1633 patients respectively. Vilanterol is currently not licensed for use. Reference: 1. Dransfield MT. Lancet Lancet Respir Med 2013;1: ; 2. Pascoe S. Lancet Respir Med 2015; 3:

24 Suggestions for management of stable COPD EOS Reactive Non-smoker Atopy Step 3 EOS Fixed Recurrent exac/infection Add ICS LABA/LAMA +/- Antibiotics Step 4 Dr. Stephen Child s suggestion for management of stable COPD (Dr. Stephen Child, Auckland City Hospital, Auckland, NZ)

25 26 yo male presents with SOB and bilateral wheeze x 3/7. Past Hx : childhood asthma Meds: Salbutamol prn only Which of the following is non- contributory? 1. BMI =38 2. Use of Diclofenac prn 3. Regular THC user 4. Use of Panadol 2-4 per day 5. Car enthusiast Code

26 26 yo male presents with SOB and bilateral wheeze x 3/7. Past Hx : childhood asthma Meds: Salbutamol prn only RR 16 HR 80 PEF 290 ( 75% best ) IF starting ICS, which and for how long? 1. Beclo equiv ug x 6/12 2. Beclo equiv ug x 1/12 3. Beclo equiv ug x 3/12 4. Beclo equiv ug x 6/12 5. Beclo equiv > 1000 ug x 24/12 Code

27 What is the Asthma Control Test? The Asthma Control Test (ACT) has the following domains: 1 Activity limitation Shortness of breath Awaking due to asthma symptoms Reliever medication Global judgment of asthma control All items refer to the last 4 weeks and are scaled from 1 to 5. 2 The sum score indicates asthma control with values of: Last 4 weeks 20 Well-controlled Not well-controlled 5 15 Poor control The minimum clinically important difference is a 3 point change in the ACT score 3 ACT: Asthma Control Test. 1. Nathan RA et al. J Allergy Clin Immunol. 2004;113: Schatz M et al. J Allergy Clin Immunol. 2006; 117: ; 3. Schatz M et al. J Allergy Clin Immunol. 2009; 124: e1. 27

28 Randomisation* Study design: Salford Lung Study in Asthma Constant real-time data collection of all interventions/safety monitoring Breo (FF/VI) open label* FF/VI open label* 4,233 patients Patients in primary care Aged 18 years GP diagnosis of asthma Taking ICS or ICS/LABA Symptomatic Consented 64% prescribed ICS/LABA pre-randomisation 36% prescribed ICS prerandomisation Randomisation visit Routine respiratory review Device instruction Questionnaires 3 monthly phone calls (if no regular visits) 12 months of usual care Week 24 Primary endpoint ACT score End of study visit Routine respiratory review Severe exacerbations Questionnaires Usual care (ICS or ICS/LABA) During the 1-year treatment period, patients can have their maintenance treatment adjusted (stepping-up, stepping-down or switch) at the GP s/investigator s discretion as would be normal clinical practice *Randomisation stratified by Asthma Control Test (ACT) score ( 20, 16 19, or 15) and by previous asthma maintenance therapy (ICS or ICS/LABA); ACT Asthma Control Test; FF fluticasone furoate; GP general practitioner; ICS inhaled corticosteroid; LABA long-acting β 2 agonist; VI vilanterol. 1. New JP, et al. Thorax. 2014;69:1152 4; 2. Woodcock A, et al. BMC Pulm Med. 2015;15: GSK DoF SLS Asthma [RF/FFT/0058/17(1)] 28

29 Percentage of subjects with either an ACT score of 20, or an increase from baseline of 3 at week 24 80% 70% 71% Usual Care (N=1514) Breo (FF/VI) (N=1512) 60% 50% 40% 56% NNT = 6.6, 95% CI ( ) n Responder* Non-Responder (56%) 615 (44%) (71%) 396 (29%) 30% 20% 10% 0% n = 784 n = 977 Usual Care (N = 1514) Responder* FF/VI (N = 1512) Breo (FF/VI) vs. Usual Care Adjusted Odds Ratio 95% CI P-value n = 615 n = (1.71, 2.34) <0.001 The odds of achieving asthma control for subjects who initiated treatment with Breo (FF/VI) are twice the odds of achieving asthma control for subjects who continued treatment with Usual Care PEA Population: all ITT subjects who have an ACT total score of < 20 at baseline (Day 0), as recorded in the ecrf. (71% of ITT population); * Responder is defined as an ACT total score 20 or an increase from baseline of 3. ACT: Asthma control test; FF: Fluticasone furoate; PEA: Primary Effectiveness Analysis; VI: Vilanterol 1. Woodcock et al. Lancet 2017: [Accessed: September 2017] 29

30 26 yo male presents with SOB and bilateral wheeze x 3/7. Past Hx : childhood asthma Meds: Salbutamol prn only In General do you prefer? 1. Symbicort 1-2 bid and prn ( SMART ) 2. Seretide 2 bid and Salbutamol prn 3. Flixotide/QVAR and Salbutamol prn 4. Breo Ellipta 100/25 OD 5. None of the above Code

31 Omalizumab Funded Nov 1, 2014 SLA, atopic, >6 years > 28 d Prednisone Raised IgE, Max Rx (Last viewed: 06 June 2018)

32 Summary: Wheeze = Obstruction but why? Eosinophilic versus not Eosinophilic? ICS if C, D or Eosinophils? Know your favourite inhaler!

33 Number of patients Need for studies closer to everday clinical practice Generalisability of studies with strict patient criteria in asthma Asthma patients visiting doctor s office % = Asthma patients eligible for a clinical trial Clinical asthma FEV 50 85% 1 Reversibility 12% No comorbidity Pack-year <10 Regular use of ICS Symptomatic asthma Common asthma patient selection criteria: FEV % of predicted Historical reversibility 12% last 12 months No significant co-morbidity Non-smoker; if ex-smoker, less then 10 pack-years Patients selected FEV 1 forced expiratory volume in 1 second Adapted from: Herland K, et al. Resp Med. 2005;99:11 9.

34 Questions Welcome!

35 Anoro Ellipta (umeclidinium bromide/vilanterol trifenatate inhaler 62.5/25mcg per inhalation) is a fully funded medicine; Special Authority criteria apply. Maximum Daily Dose: One inhalation once daily. Prescription Medicine for long-term regular treatment to relieve symptoms in adult patients with Chronic Obstructive Pulmonary Disease (COPD). This medicine has risks and benefits. Warnings and Precautions: Not recommended for use in patients with asthma or for relief of acute symptoms or an acute exacerbation. Use care when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole), beta-blockers and in patients with severe cardiovascular disease, narrow-angle glaucoma or urinary retention. Common Side Effects: Nasopharyngitis, oropharyngeal pain, sinusitis, pharyngitis, cough, urinary tract infection, constipation, dry mouth, hypertension. Paradoxical bronchospasm may occur. Before prescribing Anoro Ellipta, please review the Data Sheet at Incruse Ellipta : In addition to the Anoro Ellipta information above which also applies to Incruse Ellipta (umeclidinium bromide), Incruse is available in a 62.5mcg per inhalation in the Ellipta device. Incruse Ellipta is a fully funded medicine. The prescriber must provide written endorsement that the patient has been diagnosed as having COPD using spirometry to access subsidy. Before prescribing Incruse Ellipta, please review the Data Sheet at

36 Incruse Ellipta (umeclidinium bromide inhaler 62.5mcg per inhalation) is a Prescription Medicine. Incruse Ellipta is indicated as a long-term maintenance bronchodilator treatment to relieve symptoms in adult patients with Chronic Obstructive Pulmonary Disease (COPD). Incruse Ellipta is a fully funded medicine. The prescriber must provide written endorsement that the patient has been diagnosed as having COPD using spirometry to access subsidy. Maximum Daily Dose: One inhalation once daily. Contraindications: Patients with severe milk-protein allergy or those who have hypersensitivity to umeclidinium or any excipients. Side Effects: Urinary tract infection, tachycardia, upper respiratory tract infection, nasopharyngitis, sinusitis, cough, dysgeusia. Warnings and Precautions: Not recommended for use in patients with asthma or for relief of acute symptoms or an acute exacerbation. Use care in patients with severe cardiovascular disease (particularly cardiac arrhythmias), narrow-angle glaucoma or urinary retention. Paradoxical bronchospasm may occur. Before prescribing Incruse Ellipta, please review the Data Sheet at Incruse and Ellipta are registered trade marks of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on

37 Breo Ellipta (fluticasone furoate/vilanterol trifenatate inhaler 100/25mcg per inhalation) is a fully funded medicine. Breo Ellipta 200/25mcg is a private purchase medicine (dose indicated in asthma only); a prescription charge will apply. Maximum Daily Dose: One inhalation once daily. Maintenance Dose: Titrate to lowest effective dose. Prescription Medicine for the regular treatment of asthma (12 years of age and older) (100/25 and 200/25mcg) and/or COPD (100/25mcg) with a FEV1<70% predicted normal (post-bronchodilator) in patients with an exacerbation history. This medicine has risks and benefits. Warnings and Precautions: Not for relief of acute symptoms or an acute exacerbation. Do not discontinue abruptly. Use care when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) or in patients with hepatic impairment, severe cardiovascular disease, pulmonary tuberculosis or chronic or untreated infections. Common Side Effects: Candidiasis of mouth and throat, headache, nasopharyngitis, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, upper respiratory tract infection, bronchitis, influenza, abdominal pain, arthralgia, back pain, pyrexia. Paradoxical bronchospasm may occur. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. The incidence of pneumonia in patients with asthma was uncommon. Avoid beta-blockers if possible. Before prescribing Breo Ellipta, please review the Data Sheet at Anoro, Incruse, Breo and Ellipta are registered trade marks of the GlaxoSmithKline group of companies. Anoro and Breo Ellipta were developed in collaboration with Innoviva Inc. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on

38 Seretide (fluticasone propionate/salmeterol xinafoate inhaler 50/25 or 125/25mcg per actuation and Accuhaler 100/50, 250/50mcg per actuation) is a fully funded medicine. Seretide 250/25mcg inhaler is a private purchase medicine; a prescription charge will apply. Maximum Daily Dose: MDI 2 puffs twice daily, Accuhaler 1 inhalation twice daily. Maintenance Dose: Titrate to lowest effective dose 1-2 times daily. Prescription Medicine for the treatment of reversible obstructive airway disease (ROAD) including asthma, and for the treatment of chronic obstructive pulmonary disease (COPD). This medicine has risks and benefits. Warnings and Precautions: Not for relief of acute symptoms. Do not discontinue abruptly. Use care when co-administering strong CYP3A4 inhibitors (e.g. ketoconazole) or in patients with pulmonary tuberculosis or thyrotoxicosis. Common Side Effects: Hoarseness/dysphonia, throat irritation, headache, oral candidiasis and palpitations. Paradoxical bronchospasm may occur. Avoid beta-blockers if possible. Before prescribing Seretide, please review the Data Sheet at Seretide and Accuhaler are registered trade marks of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on