Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

COPD Working Group ERS 2017

189 views

Published on

COPD Working Group ERS 2017

Published in: Health & Medicine
  • For the past 20 years I had been taking allergy shots and they had helped to keep my lungs clear, but after moving across country and being tested by two separate allergists who said I didn't have allergies, but chronic obstructive pulmonary disease (COPD) my allergy shots stopped. One and a half years ago I started sweating profusely, worse than during menopause. Water literally dripped off my face. Gradually it started to disappear. The less the sweating became, the more I became breathless until I was gasping for air walking across a room. My lungs started to fill up with mucus which eventually turned into pneumonia. I lost touch with reality.I started on Health Herbal Clinic COPD Herbal formula treatment in May 2017, i read alot of positive reviews on their success rate treating COPD disease through their Herbal formula and i immediately started on the treatment. Just 7 weeks into the Herbal formula treatment I had great improvements with MY breething ,I am unbelievably back on my feet again, this is a breakthrough for all COPD Patients, visit Health Herbal Clinic official website www. healthherbalclinic. net or email info@ healthherbalclinic. net.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Be the first to like this

COPD Working Group ERS 2017

  1. 1. COPD Working Group Meeting CHAIR: Marc Miravitlles DATE: Saturday 9th September 2017 TIME: 11.40–12.20 VENUE: Melia Milano Hotel, Via Masaccio 19, Milan, Italy
  2. 2. Agenda 1) Update on ‘Validation of the Concept of Control of COPD in Clinical Practice’. 2) Prioritisation of current project ideas and next steps to move one of these projects forward. 3) Any new project ideas? and how these ideas should be prioritised.
  3. 3. 1) Update on current projects Validation of the Concept of Control of COPD in Clinical Practice i) Pilot database study ii) International prospective validation study
  4. 4. Background • The concept of disease control has been extensively developed in asthma; less so in COPD. • A new definition of COPD control has been proposed, defined as: o Impact of the condition o Its clinical stability • Controlled COPD = stable low impact disease (i.e. low impact over time) • The concept of COPD control is intended as a: o Complementary management tool o Tool to support day-to-day management decisions in routine care but its practical utility requires validation in routine care
  5. 5. Low clinical impact Clinical control Stability Impact High clinical impact Cross-sectional evaluation of impact Stability (Improvement or absence of changes) Inestability (Clinical worsening) V1 V2 V3 V4
  6. 6. Pilot database study • Characterized COPD patients treated in UK routine primary care in terms of their COPD control • Evaluated the clinical implications of control status Manuscript has been published in Journal of COPD
  7. 7. Results- Control status BODEx ≤4 Mild/Moderate (n=2511) Impact (cross-sectional) (i) Clinical Features Low impact (n=126) Stability (temporal) No changes (0 exacerbations) Controlled (n=112) Worsening (≥1 exacerbations) Uncontrolled (n=14) High Impact (n=2385) Uncontrolled (n=2385) (ii) CAT Score Low Impact (n=633) Stability (temporal) No changes (0 exacerbations) Controlled (n=541) Worsening (≥1 exacerbations) Uncontrolled (n=92) High Impact (n=1878) Uncontrolled (n=1878) BODEx ≥5 Severe/Very severe (n=277) Impact (cross-sectional) (i) Clinical Features Low impact (n=0) High Impact (n=277) Uncontrolled (n=277) (ii) CAT Score Low Impact (n=71) Stability (temporal) No changes (0 exacerbations) Controlled (n=23) Worsening (≥1 exacerbations) Uncontrolled (n=48) High Impact (n=206) Uncontrolled (n=206) Mild/ Moderate COPD Severe/ Very severe COPD
  8. 8. Results- Control Status & Time to First Exacerbation No severe/very severe patients were controlled at baseline based on their clinical features
  9. 9. Results- CAT score distribution A B Severe-to-very-severe COPD Arrows indicate published cutoffs used for the definitions of control in patients with mild/moderate COPD (CAT ≤10) and severe/very severe COPD (CAT≤20) Mild-to-moderate COPD
  10. 10. Hypothesis: A status of control in COPD (low impact and clinical stability) will be associated with better clinical outcomes (reduced frequency of exacerbations and mortality and improved health-related quality of life); reduced rate of decline in lung function and/or BODE/BODEx and reduced direct COPD-related healthcare costs. International Prospective Validation Study Multicenter, international and prospective study to validate the concept of control in COPD and its implications for clinical practice
  11. 11. Objectives Primary: to evaluate, in an international cohort of routine care/ unselected COPD patients, the: • Levels of COPD control (vs poor COPD control) • Clinical implications of control status. Secondary: • Compare the utility of the COPD Control (as defined) as a tool to identify COPD impact and stability with the CAT and CCQ; • Evaluate the role of “adequate” (i.e. guideline-recommended) treatment prescribing on COPD control. • Identify demographic and clinical characteristics associated with COPD control status • Evaluate the cost-utility of patients with controlled (as compared to poorly controlled) COPD.
  12. 12. Recruitment Study power: o ≥285 patients are required to power the primary and secondary endpoints and permit subgroup analyses. o Total patient recruitment = 328 (to allow for ~12% drop outs)
  13. 13. Design: prospective non-interventional 21 months prospective pragmatic trial, comprising 5 evaluation points: one screening evaluation and 4 follow-up evaluations 3 months Visit -1 (Screening visit) Visit 0 (Screening visit) Visit 1 (Follow-up visit) Visit 2 (Follow-up visit) Visit 3 (Follow-up visit) Clinician-guided (“usual care”) treatment throughout the study Screening assessment Baseline assessment Control 1 Control 2 Control 3 Currently-completing Visit 1 and starting Visit 2 6 months (15 months from screening visit) 6 months (9 months from screening visit) 6 months (21 months from screening visit)
  14. 14. Recruiting Investigators & Centres Country Site Name Principal Investigator Ireland Royal College of Surgeons, Dublin Richard Costello Spain Pneumology Department, Vall d' Hebron University Hospital, Barcelona Marc Miravitlles Pneumology Department, Hospital de Laredo, Laredo Juan Luis Garcia-Rivero Respiratory Department, Hospital de Alta Resolucion, Granada Bernardino Alcazar Navarrete Instituto de Investigacíon Sanitaria de Palma (IdISPa), Palma de Mallorca Miguel Roman Rodriguez Singapore Singapore General Hospital Jessica Tan (formerly Therese Lapperre) Changi General Hospital (CGH) Augustine Tee Korea Department of Internal Medicine, Seoul St. Mary's Hospital Chin Kook Rhee UK Optimum Patient Care Clinical Review Service David Price Poland Institute of Tuberculosis and Lung Diseases, Warsaw Pawel Sliwinski Malta Department of Respiratory Medicine, Mater Dei Hospital, Msida Caroline Gouder Recruitment is now complete
  15. 15. Timelines Study Element Completion dates Ethics & contracts October 2015–April 2016 Recruitment May 2016–November 2016 Baseline analysis March 2017 Follow up 1 completed September 2017 Follow up 2 completed March 2018 Follow up 3 completed and all data complied November 2018 Final report, including longitudinal study and control measurements March 2019 Final manuscript September 2019
  16. 16. Current status • 339 patients enrolled • 324 (95.6 %) of patients completed Baseline visit • 297 (87.6 %) of patients completed Follow-up 1 visit • 18 (5.3 %) of patients completed Follow-up 2 visit • 26 patients have withdrawn since the Screening visit
  17. 17. Demographic & clinical characteristics of the patient population. All (n=314) Controlled (n=67) Uncontrolled (n=247) P value Age, years 68.5 (8.7) 67.9 (8.5) 68.7 0.53 Sex, men (%) 225 (72.5) 58 (89.2) 167 (68.1) 0.001 Living status (%): Alone Couple or relatives 60 (19.3) 248 (80) 8 (12.3) 56 (86.5) 52 (21.1) 192 (77.3) 0.09 Education (%): Up to primary Secondary Some university 95 (30.2) 157 (50) 61 (19.4) 13 (19.4) 33 (49.3) 21 (31.3) 82 (33.2) 124 (50.2) 40 (16.2) 0.14 Active smokers 82 (26.1) 49 (73.1) 180 (72.9) 0.66 Pack-years 47.7 (31.1) 42.7 (23.2) 49.7 (34.1) 0.08 BMI (Kg/m2) 26.4 (5.3) 25.3 (4.9) 26.7 (5.4) 0.09 Chronic bronchitis 162 (61.3) 27 (48.2) 135 (73.5) 0.023 Emphysema 198 (75) 45 (80.3) 153 (73.5) 0.29 ACO 30 (9.6) 8 (11.9) 22 (8.9) 0.46 Bronchiectasis 40 (12.8) 11 (16.6) 29 (11.8) 0.29 Charlson index 4.2 (1.6) 3.9 (1.7) 4.3 (1.6) 0.049 mMRC 1.62 (1) 0.85 (0.3) 1.83 (1) <0.001 FVC FVC (%) FEV1 FEV1 (%) 2880 (892) 67.5 (14.5) 1489 (582) 52.6 (18) 3189 (953) 71.6 (16.1) 1758 (633) 58.3 (18.3) 2780 (860) 65.8 (14.1) 1416 (546) 51 (17.7) 0.002 0.019 <0.001 0.003 Exacerbations previous year 1.27 (2.7) 0.54 (1.2) 1.47 (3) 0.004 CAT score 14.3 (8.7) 12.2 (7.6) 14.8 (8.9) 0.043 CCQ score 2.03 (1.3) 1.77 (1.3) 2.1 (1.3) 0.033 Minutes walked/day 82.2 (76.6) 117.7 (56) 72.3 (78.7) <0.001
  18. 18. Treatment patterns SAMA/SABA alone or in combination 1.1 1.8 1 0.60 LABA 10.5 12.4 10.2 0.66 LAMA 18.3 25.8 16.3 0.07 ICS 0.6 0 0.8 0.46 LABA/LAMA 26.3 28.8 25.6 0.60 ICS/LABA 11.2 7.6 12.2 0.29 ICS/LAMA 1.9 3 1.6 0.46 ICS/LABA/LAMA 25 15.2 27.6 0.037 COPD treatment category of controlled and uncontrolled patients All Controlled Uncontrolled P-value
  19. 19. Factors accounting for the uncontrolled status patients Patients with high impact or instability due to: All (n=314) Mild/moderate (n=276) Severe (n=39) Impact variables Dyspnea (mMRC) 101 (36.7) 33 (84.6) 134 (42.6) Rescue medication 60 (21.7) 14 (35.9) 74 (23.5) Physical activity 86 (31.1) 12 (30.7) 98 (31.2) Sputum 42 (15.2) 10 (25.6) 52 (16.6) Any clinical criteria 173 (62.7) 38 (97.4) 211 (67.2) CAT score 165 (59.8) 23 (58.9) 188 (59.8) CCQ score 189 (68.5) 29 (74.3) 218 (66.5) Stability variables Exacerbations 49 (17.7) 20 (51.2) 69 (21.9) Changes in CAT 87 (31.7) 15 (38.4) 102 (32.6) Changes in CCQ 127 (46.3) 19 (48.7) 146 (46.6) Any exacerbations or changes in CAT 116 (42.2) 26 (66.6) 142 (45.2) Uncontrolled 208 (75.6) 39 (100) 247 (78.6)
  20. 20. Backwise logistic multivariate model to control. Unadjusted OR (CI 95%) P value Adjusted OR (CI 95%) P value Age, years 0.99 (0.96-0.02) 0.53 Sex (male) 3.87 (1.68-8.86) 0.001 3.57 (1.16-10.92) 0.019 Living alone 0.52 (0.23-1.16) 0.09 Higher academic education 2.24 (1.09-4.59) 0.02 BMI, Kg/m2 0.94 (0.90-1.002) 0.057 Charlson index 0.85 (0.69-0.95) 0.049 Chronic bronchitis 0.50 (0.27-0.91) 0.024 0.55 (0.29-0.93) 0.04 Previous exacerbations 0.41 (0.22-0.77) 0.005 0.45 (0.22-0.91) 0.049
  21. 21. Evaluation of low impact, stability and control of COPD using different criteria: clinical, CAT or CCQ questionnaires. Impact: clinical1 Stability: EX Impact: CAT Stability: CAT Impact: CCQ Stability: CCQ Impact: clinical1 Stability: EX & CAT Impact: CAT Stability: EX & CAT Impact: clinical1 & CAT Stability: EX & CAT Impact: clinical1 & CCQ Stability: EX & CCQ BODEx ≤4 versus ≥5 Low Clinical Impact 104 (33) 127 (40) 91 (29) 104 (33) 127 (40) 55 (18) 44 (14) Stable 246 (78) 211 (67) 215 (70) 172 (55) 172 (55) 172 (55) 177 (57) Control of COPD 99 (32) 101 (32) 83 (27) 67 (21) 89 (28) 42 (13) 40 (13) BODEx ≤2 versus ≥3 Low Clinical impact 126 (40) 171 (54) 129 (42) 126 (40) 171 (54) 82 (26) 63 (20) Stable 246 (78) 172 (55) 215 (70) 172 (55) 172 (55) 172 (55) 177 (57) Control of COPD 117 (37) 117 (37) 113 (37) 83 (27) 117 (37) 62 (20) 53 (17)
  22. 22. 2) Current ideas for future studies • Implications of ICS withdrawal in the real-life management of COPD (Real-life WISDOM). • Modern epidemiology of alpha-1-antitrypsin deficiency (AATD) in the UK. • Claims-based validation of a UK COPD Risk Prediction model. • Comparative effectiveness of triple therapy vs recommended dual therapy (ICS/LABA and LAMA/LABA) treatment in patients with COPD Need to prioritise these projects
  23. 23. Withdrawal of ICS in COPD (Real-life WISDOM)
  24. 24. Background 1. Wouters EF, et al. Thorax. 2005;60:480-7; 2. Lapperre TS, et al. Ann Intern Med. 2009 Oct 20;151:517-27. 3. van der Valk P, et al. Am J Respir Crit Care Med. 2002;166:1358-63. 4. Kunz LI, et al. Chest. 2015;148:389-96. 5. Magnussen H, et al. NEJM. 2014;371:1285-94 • Withdrawal of ICS therapy (vs. combination ICS/LABA) is associated with:1–3 o Increased exacerbations and symptoms o Reduced quality of life o Accelerated lung function decline. • ICS lack sustained disease-modifying effects, as assessed by lung function decline, AHR, and QOL following ICS cessation.4 • WISDOM evaluated the effect of gradual ICS withdrawal in COPD patients (n=2485) on triple therapy (ICS/tio/salmeterol) within an RCT environment and observed that discontinuation of ICS did not affect:5 o Exacerbation rates. o Outcomes in subgroups in which a greater degree of dependence on ICS might be expected. o Rate of dropout. But resulted in a greater decrease in lung function.
  25. 25. Aim Evaluate the effect of ICS cessation (and reduced ICS exposure) on COPD lung function (and exacerbation rates) in patients with COPD managed in a routine care, “real-life” setting.
  26. 26. Study Design Using primary care records data from the UK’s Optimum Patient Care Research Database (OPCRD) Index date Cohort A – Control Arm: continue on baseline therapy (no MPR restrictions) Baseline Patients on FDC ICS/LABA and separate LAMA ICS MPR ≥70% 1 year 1 year Annual exploratory endpoints to 5 years post index date Month -12 Month -6 Month 12 Month 13 Month ……………………………..60 Month 0 Month 3 Cohort A – Cessation Arm: LABA / LAMA therapy (any combination of fixed or separate inhaler devices) No ICS prescriptions fro ≥3 months (i.e. prior to month 3) ICS Cessation Cohort ICS Reduction Cohort Index date Cohort B – Control Arm: continue on baseline therapy (at no or <50% reduction in ICS dose) Baseline Patients on: ICS/LABA/LAMA (any fixed or free combinations) ICS MPR ≥70% 1 year 1 year Annual exploratory endpoints to 5 years post index date Month -12 Month -6 Month 12 Month 13 Month ……………………………..60 Month 0 Month 3 Cohort B – Reduction Arm (prescribed): continue on baseline therapy but with ICS prescribed at ≥50% reduced dose
  27. 27. Endpoints Primary endpoints • Time to first acute COPD exacerbation Secondary endpoints • Exacerbation rate • Change in FEV1 • Treatment stability (absence of exacerbations and no escalation in pharmacotherapy) • COPD-related hospitalisations (rate and time to first) The interaction between the following patient / clinical features and the study outcomes will be explored where feasible: • Baseline blood eosinophil level • Baseline exacerbation rate • Presence of atopy • Smoking status (current vs ex-) • Prescribed baseline ICS particle size (extra-fine vs non-extra-fine) Interaction analyses
  28. 28. Modern epidemiology of alpha-1-antitrypsin deficiency (AATD) in the UK
  29. 29. Background • Alpha1-antitrypsin deficiency (AATD) is a genetic condition characterized by low serum levels of AAT (also known as alpha-1 proteinase inhibitor). • AAT protects the alveoli from damage by proteolytic enzymes1. • Emphysema in AATD is thought to occur as the reduced AAT levels can no longer protect the elastin from degradation by neutrophil elastase. • Cigarette smoking and infection increase elastase production in the lung, thus increasing lung degradation.1 • AATD is considered a rare disease (3.4 million individuals worldwide) , but it is believed to be largely underdiagnosed2. • Estimates of AATD prevalence in the UK are outdated3–7. • The National Institute for Health and Care Excellence in the UK is currently reviewing AATD treatment and management recommendations8. 1. Stoller JK, et al. Am J Respir Crit Care Med 2012; 185:246. 2. de Serres FJ, et al. Chest 2002;122:1818– 1829. 3. Hutchison DC, et al. Clin Sci 1970;38:19P. 4. Cook PJ, et al. Ann Hum Genet 1975;38:275-87. 5. Hutchison DC, et al. Bull Eur Physiopathol Respir 1980;16 Suppl:315-9. 6. Hutchison DC. Lung 1990;168 Suppl:535-42. 7. Jones RJ, et al. LRM. 2014;2:267-76. 8. NICE. Proposed HTA Human alpha1-proteinase inhibitor for treating emphysema Draft scope (pre-referral); March 2016.
  30. 30. Study Aim • Determine the epidemiological trends (1990-2015) of Alpha1-antitrypsin deficiency (AATD) in the UK, and its natural history in the population: o Size of the problem o Prevalence o Incidence o Mortality • Benchmark AATD with other respiratory and non- respiratory conditions
  31. 31. Data sources • A combined dataset of patients from two UK primary care databases (de-duped) will be used: o Clinical Practice Research Database o Optimum Patient Care Research Database (OPCRD) • Subpopulation data links – where available: o Rates of hospitalisations and day cases of treatment for AATD will be assessed in patients with linked Hospital Episode Statistics (HES) data o Mortality rate and cause of death will be assessed in patients with linked Office of National Statistics (ONS) data
  32. 32. Study Design Three cohort populations: AATD cohort COPD cohort (clinical comparator) General Population (population reference) Patients will be matched on age, sex, calendar year
  33. 33. Outcomes Co-Primary endpoints (stratified by year) • AATD Incidence • AATD Prevalence • AATD mortality rates. Secondary endpoints • Respiratory exacerbations • Oral steroids courses • Inpatient hospitalisations for AATD o Respiratory, liver, or other, as per HES statistics • Day cases for AATD treatment • Other clinical outcomes of particular interest include: o Oxygen saturation, imaging, Charlson index, mMRC dyspnoea, … Subgroup of AATD patients with liver disease: • Child-Pugh score
  34. 34. But first… a pilot Data source: OPCRD only (no linked secondary or mortality data). Population: AATD diagnosis only (i.e. no matched comparisons) Exploratory patient number: 100 Primary endpoints (stratified by year) • AATD Incidence • AATD Prevalence • AATD mortality rates. Secondary endpoints • Respiratory exacerbations • Oral steroids courses • Other clinical outcomes of particular interest (Oxygen saturation/ imaging/ Charlson index/ mMRC dyspnea) Dataset is already available for this pilot analysis
  35. 35. Claims-based validation of a UK COPD Risk Prediction model. REG has developed a risk prediction tool using routinely collected primary care data from the UK to identify patients are increased risk of multiple COPD exacerbations Calibration plot of observed vs predicted risk using the full developmental model (N=16,565) Calibration plot (25 groups of 108-109 observations) of observed vs predicted risk after applying the model to the validation cohort (N=2,713)
  36. 36. Claims-based validation of a UK COPD Risk Prediction model. Aims: 1) Develop an equivalent model using administrative insurance claims data to identify patients at increased risk of multiple COPD exacerbations. 2) Test the external validity of the UK model by seeking to validate it in a claims-based healthcare system.
  37. 37. Aim: The study will evaluate the comparative effectiveness of different (guideline- recommended) treatment options as prescribed in a UK routine care population with confirmed COPD, eligible for triple therapy, specifically: (A) LAMA versus ICS/LAMA/LABA (B) ICS/LABA versus ICS/LAMA/LABA (C) LAMA/LABA versus ICS/LAMA/LABA Comparative effectiveness of triple therapy vs recommended dual therapy (ICS/LABA and LAMA/LABA) treatment in patients with COPD
  38. 38. Triple therapy in COPD Index Date: Date of: •Active arm: date of repeat LAMA prescription, or •Control arm: first ICS/LABA prescription LAMA therapy Patients characterized for confounder definition Outcomes evaluated for comparator arms following matching based on key clinical and demographic characteristics during baseline LAMA therapy Baseline 12 months Outcome12 months Triple Therapy Arm LAMA/LABA/ICS Index Date: Date of: •Active arm: first LAMA prescription, or •Control arm: repeat ICS/LABA prescription Triple Therapy Arm LAMA/LABA/ICS Baseline 12 months Outcome12 months Matched Analysis A Matched Analysis B Study Design Historical matched cohort study using electronic medical records and linked questionnaire data from the Optimum Patient Care Research Database (OPCRD) Similar matched analyses with be carried out for: ICS/LABA vs ICS/LABA/LAMA and LAMA/LABA vs ICS/LAMA/LABA Outcomes: • Time to first exacerbation • Exacerbation rate • Hospitalisations for COPD/ lower resp events • Change in MRC score • Incidence of pneumonia
  39. 39. Next steps…. • Implications of ICS withdrawal in the real-life management of COPD (Real-life WISDOM). - Dr Postma who was leading this project has retired. New lead required. - Is there interest in moving this forward? • Modern epidemiology of alpha-1-antitrypsin deficiency (AATD) in the UK. - Originally no interest from funders - Data is available to carry out pilot, do we want to proceed with this pilot? • Claims-based validation of a UK COPD Risk Prediction model. • Comparative effectiveness of triple therapy vs recommended dual therapy (ICS/LABA and LAMA/LABA) treatment in patients with COPD Is there still interest in these projects? Which of these projects is highest priority? How can we move one of these projects forward?
  40. 40. REG projects with a COPD component Clinical and Cost implications of OLDOSA The term “OLDOSA syndrome” has been proposed1, which refers to the coexistence of OLD (obstructive lung disease: COPD and asthma) and OSA 1. Ioachimescu OC, et al. Respirology. 2013;18:421-31 AIMS: Evaluate the impact of (i) continuous positive airway pressure (CPAP) therapy (ii) a sleep breathing disorder diagnosis (as a proxy for CPAP treatment) (iii) an OSA diagnosis on clinical outcomes and healthcare resource utilisation in UK patients with comorbid OLD Obstructive sleep apnoea WG are looking for anyone interested in being involved
  41. 41. 3) Any new project ideas? How should these be prioritised with the existing project ideas?

×