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 WG summit 2018

4 views

Published on

WG Summit 2018

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

COPD WG summit 2018

  1. 1. COPD Working Group Meeting CHAIR: Marc Miravitlles DATE: Thurday 22nd March 2018 TIME: 16.30–17.30 VENUE: Park Plaza Hotel, Amsterdam Airport
  2. 2. Agenda 1) Update on current projects a) ‘Validation of the Concept of Control of COPD in Clinical Practice’. b) Alpha1-Antitrypsin Deficiency (AATD) pilot study 2) Discussion of plans for future work a) Real-life WISDOM b) Full AATD study 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 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. 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
  6. 6. 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
  7. 7. 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.
  8. 8. 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 centres are completing Visit 2 and starting Visit 3 6 months (15 months from screening visit) 6 months (9 months from screening visit) 6 months (21 months from screening visit)
  9. 9. 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
  10. 10. 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
  11. 11. Current status • 339 patients enrolled • 327 (96.5 %) patients completed Baseline visit • 312 (92.0 %) patients completed Follow-up visit 1 • 234 (69.0 %) patients completed Follow-up visit 2 • 1 (0.2%) patient completed Follow-up visit 3 • 30 patients have withdrawn since the Screening visit
  12. 12. Results so far… Manuscript on the findings from the baseline visit has been published
  13. 13. 1) Update on current projects Modern epidemiology of alpha-1- antitrypsin deficiency (AATD) in the UK - a pilot study
  14. 14. 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.
  15. 15. STROBE flowchart of participants in this pilot study
  16. 16. C) Incidence of AATD in males by age D) Incidence of AATD in females by age E) Incidence of AATD by sex A) Frequency of new AATD testing by gender B) Frequency of new AATD testing by age Trends of several incidence AATD indicators from 1990 to 2014, with their 95% exact binomial confidence intervals
  17. 17. A) Frequency of any testing of AATD by gender B) Frequency of any testing of AATD by age C) Prevalence of AATD in males by age D) Prevalence of AATD in females by age E) Prevalence of AATD testing by gender Trends of several prevalence AATD indicators from 1990 to 2014, with their 95% exact binomial confidence intervals
  18. 18. n AATD/ N COPD Percentage & 95% C.I. Both genders 20-44 years 59/212 27.8 (21.9-34.4) 45-64 years 95/431 22.0 (18.2-26.3) 65+ years 3/20 15.0 (3.2-37.9) All 157/663 23.7 (20.5-27.1) Female 20-44 years 13/86 15.1 (8.3-24.5) 45-64 years 46/218 21.1 (15.9-27.1) 65+ years 0/9 0.0 (0.0-33.6) All 59/313 18.8 (14.7-23.6) Male 20-44 years 46/126 36.5 (28.1-45.6) 45-64 years 49/213 23.0 (17.5-29.2) 65+ years 3/11 27.3 (6.0-61.0) All 98/350 28.0 (23.4-33.0) Prevalence of AATD as the percentage of those COPD individuals tested, by gender and age
  19. 19. AATD patients (n=157) Non-AATD patients (n=506) P-value Age at COPD diagnosis mean±SD 46.4±7.8 47.7±7.7 0.061 Age at AATD testing mean±SD 48.3±9.0 49.9±9.2 0.016* Gender n(%) Female 59 (37.6%) 254 (50.2%) 0.007* Male 98 (62.4%) 252 (49.8%) BMI (kg/m2) n(%) Underweight 11 (7.3%) 35 (7.2%) 0.066 Normal 74 (49.3%) 200 (40.9%) Overweight 42 (28.0%) 129 (26.4%) Obese 23 (15.3%) 125 (25.6%) Missing 7 (4.5%) 17 (3.4%) Smoking status n(%) Current Smoker 56 (36.8%) 260 (51.7%) 0.004* Ex-Smoker 75 (49.3%) 179 (35.6%) Non-Smoker 21 (13.8%) 64 (12.7%) Missing 5 (3.2%) 3 (0.6%) GOLD Spirometric Severity n(%) Mild 20 (14.6%) 76 (16.0%) <0.001* Moderate 37 (27.0%) 225 (47.4%) Severe 44 (32.1%) 127 (26.7%) Very Severe 36 (26.3%) 47 (9.9%) Missing 20 (12.7%) 31 (6.1%) FEV1 percentage of predicted n(%) <10% 0 (0.0%) 2 (0.4%) <0.001* ≥10<20% 9 (6.6%) 14 (2.9%) ≥20<30% 27 (19.7%) 31 (6.5%) ≥30<40% 26 (19.0%) 65 (13.7%) ≥40<-50% 18 (13.1%) 62 (13.1%) ≥50<60% 7 (5.1%) 78 (16.4%) ≥60<70% 14 (10.2%) 78 (16.4%) ≥70<80% 14 (10.2%) 67 (14.1%) ≥80<90% 9 (6.6%) 33 (6.9%) ≥90% 13 (9.5%) 45 (9.5%) Missing 20 (12.7%) 31 (6.1%) GOLD 2017 Risk n(%) A 24 (24.0%) 128 (29.4%) 0.018* B 7 (7.0%) 61 (14.0%) C 39 (39.0%) 108 (24.8%) D 30 (30.0%) 138 (31.7%) Missing 57 (36.3%) 71 (14.0%) Annual exacerbation rate (in the year prior to AATD testing) 0 80 (51.0%) 201 (39.7%) 0.11 1 30 (19.1%) 126 (24.9%) 2 21 (13.4%) 71 (14.0%) 3 9 (5.7%) 47 (9.3%) 4 11 (7.0%) 30 (5.9%) 5 5 (3.2%) 15 (3.0%) 6+ 1 (0.6%) 16 (3.2%) Demographic & clinical characteristics of individuals tested positive or negative for AATD.
  20. 20. • Despite an increase in the frequency of AATD testing since 1990, only 2.2% of patients diagnosed with COPD before the age of 60 years were tested. • Given an AATD prevalence of 23.7% in those tested, it appears that AATD remains largely underdiagnosed in COPD patients in the UK. Conclusions
  21. 21. 2) Future studies seeking funding a) Full AATD study b) Real-life WISDOM
  22. 22. Modern epidemiology of alpha-1-antitrypsin deficiency (AATD) in the UK - Full study
  23. 23. Study Aim • Determine the epidemiological trends (1990-2017) 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
  24. 24. 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
  25. 25. Study Design Three cohort populations: AATD cohort COPD cohort (clinical comparator) General Population (population reference) Patients will be matched on age, sex, calendar year
  26. 26. 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
  27. 27. Withdrawal of ICS in COPD (Real-life WISDOM)
  28. 28. 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 in exacerbations and symptoms; o Reduced health-related quality of life o Accelerated lung function decline. ICS lack sustained disease-modifying effects as assessed by lung function decline, airway hyper responsiveness, 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:5 o Did not affect exacerbation rates. o Did not affect outcomes in subgroups where a greater dependence on ICS might be expected. o Did not affect the dropout rate. o Resulted in a greater decline in lung function during the final step of ICS withdrawal.
  29. 29. 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.
  30. 30. Study Design Cohort A: ICS Cessation Cohort B: ICS Reduction Two, two-way matched analyses using primary care records from the UK’s Optimum Patient Care Research Database (OPCRD) 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 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) Index date Annually to 5 yearsBaseline: 1 year 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 3 months & 1 year Patients on FDC ICS/LABA and separate LAMA ICS medication possession ratio (MPR) ≥ 70 % Patients on ICS/LABA/ LAMA (any fixed or free combinations) ICS medication possession ratio (MPR) ≥ 70 % Outcome periods: Patients on fixed dose combination ICS/LABA and separate LAMA ICS medication possession ratio (MPR) ≥ 70 % Patients on ICS/LABA/ LAMA (any fixed or free combinations) ICS medication possession ratio (MPR) ≥ 70 % Cessation arm- LABA/LAMA therapy. No ICS prescription for at least 3 months from index date. Control arm- continue on baseline therapy (no MPR restrictions Control arm- continue on baseline therapy, with no or <50% reduction in ICS dose. Reduction arm- continue on baseline therapy, but ICS prescribed at ≥50% reduced dose.
  31. 31. Outcomes 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)
  32. 32. 3) Any new project ideas? How should these be prioritised with the existing project ideas?

×