reg copd control working group meeting 25/9/15

2015 ERS EVENTS

DATE: FRIDAY SEPTEMBER 25TH

VENUE: Wyndham Apollo Hotel, AmsterdamMEETING ROOM: BoardroomTIME: 15:30-17.00PM

CHAIR: Marc Miravitlles, Chest Physician and Senior Researcher in the Department of Pneumology at the Hospital Universitari Vall d’Hebron

COPD CONTROL WORKING GROUP MEETING

Agenda

Lowclinical impact

Clinical control

Stability

Impa

ctHighclinical impact

Cross-sectional evaluationof impact

Stability(Improvement or

absence of changes)

Inestability(Clinical worsening)

V1 V2 V3 V4

Definition of Control

Concept & Validation:

• Concept:o Control is not a prediction toolo Concept of control can potentially be used

to motivate and educate patientso It may help to step up or down treatment

and establish the frequency of clinical visits

• Validation of Clinical Validity & Utility:o Prospective trial pilot work in Spain (x2 studies)o Database pilot work in the UK (x1 study)o International prospective trial

STUDY 1: changes in control vs changes in severity over 6 monthsSTUDY 2: comparison of control and symptoms over 6 months

Observational Pilot Work in Spain

Study 1: changes in control vs severity

• Objectiveso Compare variability in control with variability in

severity (FEV1 and BODE/BODEx) over a 6-month observational outcome period.

• Update / results summaryRecruitment started in July 2015. Participating centers: 40Patients recruited at Sep 15th: 89Objective: 400 patients included

Study 2: comparison of symptoms & control

• Objectiveso Compare the changes in control with the prevalence and

changes in EXACT Respiratory Symptoms (E-RS).

• Update / results summary6 mo. FU and 3 visitsSample size 150 ptsAt ethics c. of different centersDeveloping the eCRF and questionnaire by smart

phones

Cross-sectional, non-interventional database study using the Optimum Patient Care Research Database (OPCRD) as a lead-in to the prospective trials

UK Database pilot

Criteria to establish degree of control:

Soler-Cataluña et al. ERJ. 2014;44:1069-72

Validation of concept study:

Aims: • Characterize COPD patients treated in UK routine primary care in terms of

their COPD control • Evaluate the clinical implications of control status

Data sources:• The UK’s Optimum Patient Care Research Database (OPCRD)• Fully anonymised UK primary care data• Historical medical records for >2.2 million patients from >550 primary care

practices across the UK • Ethical approval for medical research & used for multiple peer-review

publications

Study Design:

• 12- and 3-month baseline periods & 1-year outcome period• An index date: the date of receipt of the patients completed

COPD Assessment Test (CAT)

Inclusion/Exclusion Criteria:

Inclusion CriteriaCOPD diagnosis (physician-diagnosed COPD),

Aged ≥40 years

Current or ex-smokers

Recorded COPD Questionnaire data• ≥3 months continuous clinical records immediately prior to the index date• ≥1 year of continuous clinical records immediately following the index date

Exclusion Criteria

Any chronic respiratory condition other than COPD, asthma or bronchiectasis (e.g. cystic fibrosis, lung fibrosis)Patients with potential severe comorbidity at index date, defined as those with a recorded data of death within the 24 months following index date

COPD Severity: BODEx Index

Body mass index, airflow Obstruction; Dyspnea, and Exacerbations (BODEx) index:

COPD Control defines a BODEx of: • ≤4 points as mild/moderate COPD• ≥5 points as severe/very severe COPD

Patient BODEx

BODEx Score COPD Patients n, (%)

0 592 (21.23)

1 647 (23.21)

2 551 (19.76)

3 430 (15.42)

4 291 (10.44)

5 148 (5.22)

6 86 (3.03)

7 34 (1.20)

8 9 (0.38)

Total 2788 (100)

Mild to moderate

Severe to very severe

Definition of COPD impact, by COPD severity

^ Sputum colour is not routinely collected in the OPC COPD questionnaire. The question:“I have no phlegm (mucus) on my chest” will be used as a proxy*CCQ is not currently captured in the OPCRD, so only the CAT score will be used

Low impact: all criteria must be satisfied;High impact: fulfillment of any criterion of high impact results in a classification of high impact

Stability Measures

• Stability assessed by the presence or absence of exacerbations

• Changes in CAT/CCQ scores could not be evaluatedo CCQ scores are not collected in the OPCRDo Only CAT score at IPD evaluated

Patient control status:Excluded:1. Patients with no MRC Score (n=

179)2. Patients with incomplete CAT

Questionnaire (n= 502)3. No BMI data (n= 80)

Controlled COPD Patients:

Total of 2788 patients assessed

Low impact*

Mild to moderate(BODEx ≤4)n=2511

Severe to very severe (BODEx ≥5)n=277

Number of patients excluded, n

Dyspnea (mMRC) 987 249

Rescue medication 1064 25

Daily physical activity 261 2

CAT Score 100 1Sputum Colour 1 -Exacerbations 9 -Total Excluded 2422 277Total Included 89 0

Summary of patients excluded during analysis of low impact and stability

*Low impact: all criteria must be satisfied. Therefore a sequential analysis was completed

Uncontrolled COPD Patients:

Total of 2788 patients assessed

High impact

Mild to moderate (BODEx ≤4)

Severe to very severe (BODEx ≥5)

Number of patients that did not fulfill the specific criteria, n

Dyspnea (mMRC) 1436 28

Rescue medication 549 20

Daily physical activity 806 105

CAT Score 553 71

Sputum Colour 2199 171

Summary of the number of patients that did not fulfill the specific criteria*

*High impact: fulfillment of any criterion of high impact results in a classification of high impact

ALL patients fulfilled one or more of the criteria

Descriptive Analysis: Demographics

Demographics COPD Cohort (n=2788)

Control Status

Controlled(n= 89)

Uncontrolled (n=2699) p-value

Age (years), Median (IQR) 71 (94, 42) 71 (82, 52) 71 (94, 42) 0.349*

Gender, n (% male) 1630 (58.46) 56 (62.92) 1574 (58.32) 0.444*

Smoking Status

Current 806 (28.91) 33 (37.08) 773 (28.64)

0.084**Former 1982 (71.09) 56 (62.92) 1926 (71.36)

Non 0 0 0

*Mann-Whitney U test**Chi Square

Descriptive Analysis: Comorbidities

Evidence of comorbidities (in study period), n (%)

COPD Cohort (n=2788)

Control Status

p-value*Controlled

(n=89)Uncontrolled

(n=2699)

Asthma 833 (29.88) 15 (16.85) 818 (30.31) 0.006

Cardiovascular disease 1122 (40.24) 36 (40.45) 1086 (40.24) 0.999

Ischemic Heart Disease 621 (22.27) 21 (23.60) 600 (22.23) 0.796

Heart Failure 178 (6.38) 3 (3.37) 175 (6.48) 0.280

Hypertension 168 (6.03) 5 (5.62) 163 (6.04) 0.999

Diabetes 710 (25.47) 22 (24.72) 688 (25.49) 0.903

Bronchiectasis 142 (5.09) 2 (2.25) 140 (5.19) 0.239

Rhinitis 342 (12.27) 13 (14.61) 329 (12.19) 0.510

Eczema 567 (20.34) 15 (16.85) 552 (20.45) 0.428

Osteoporosis 348 (12.48) 5 (5.62) 343 (12.71) 0.049

Gastroesophageal reflux disease 274 (9.38) 8 (8.99) 266 (9.86) 0.859

Chronic Kidney Disease 480 (17.22) 10 (11.24) 470 (17.41) 0.153*Mann-Whitney U test

Results: Exacerbations

*Mann-Whitney U test

Group Mean time (days) to first COPD exacerbation ( SD, median, range) p value*

Controlled (n=89) 161.95 (104.06, 172.5, 17-359)0.163

Uncontrolled (n=2699) 130.42 (97.87, 110, 1-365)

*Count of exacerbation events (acute oral steroids, antibiotics with respiratory event, emergency and inpatient respiratory admissions). Events within 2 weeks are assumed to be the same exacerbation

**Mann-Whitney U test

Exacerbations*

Baseline Outcome

Total Controlled Uncontrolled Total Controlled Uncontrolled p** value

Yes n (%) 661 (23.71) 0 661 (24.49) 1190 (42.67) 20 (22.47) 1170 (43.35)

<0.0001No n (%) 2127 (76.29) 89 (100) 2038 (75.51) 1598 (57.32) 69 (77.53) 1529 (56.65)

Total 2788 (100) 89 (100) 2699 (100) 2788 (100) 89 (100) 2699 (100)

Exacerbations baseline and outcome:

Time to first exacerbation:

*Mann-Whitney U test

Summary:

• In a COPD cohort of 2788 patients, only 89 patients (3.19%) were defined as Controlled, using the definitions outlined in Soler-Cataluña et al. 2014

• Uncontrolled patients in the baseline were more likely to have exacerbations in the outcome period than Controlled patients (43% vs. 22%)

• Time to first exacerbation in outcome period was shorter for COPD Uncontrolled patients

Limitations:

• Various proxies used for BODEx • Sputum proxy• CCQ is not currently captured in the OPCRD, so only

the CAT score (at index date) assessed• Stability measures proxy

• Using only exacerbations in prior 3-months

Next steps:• Steering committee review & discussion of possible sensitivity

analyses to explore the proxies / thresholds used• Exploration of sputum codes to replace sputum proxy• Exploration of prescribed SABA dose as an alternative to CAT

reliever question proxy for symptoms criterion• Determine if there is a difference between patients controlled vs

uncontrolled in terms of:o Exacerbation rate over the 1-year outcome periodo Demographic and clinical characteristics associated with poor

COPD control, including:– Age, Sex, Height, Weight, Therapy, Airway Obstruction,

Smoking History

21.4 ± 7.1

26.2 ± 6.5

31.1 ± 5.9

16.6 ± 7.1

p<0.0001

I III

II IV

Niveles de gravedad (GesEPOC) y CAT (impacto)

Pro

porc

ión

de p

acie

ntes

(%)

TOTAL0

25

50

75

100

40.4%

59.6%

Loja Requena

42.6%

57.4%

24.3%

75.7%

p<0.001

Control en EPOC: proyectos de investigación4

Estudios descriptivos: Loja/RequenaControl clínico

Mal control


Estudios descriptivos: Loja/Requena

Loja(Granada)

(n=116)

Requena(Valencia)(n=107) p

Edad 71 ± 10 71 ± 9 NS

Género (Hombres, %) 100 93 0,003

Tabaquismo activo (%) 28 11,6 0,002

FEV1 postbd (%) 57 ± 17 53 ± 17 NS

CAT basal (±SD) 19,0 ± 7,9 11,3 ± 7,2 <0,001

Fenotipo clínico:- No agudizador- Mixto (EPOC-Asma)- Agudizador con enf.- Agudizador con BC.

31,924,111,232,8

55,715,714,813,9

<0,001

BODEx:- Q1 (0 – 2)- Q2 (3 – 4)- Q3 (5 – 6)- Q4 (7 – 10)

52,236,311,5

0

55,333,39,61,8

NS

Tratamiento:- LAMA- LABA- LAMA+LABA- LABA+CsI- LAMA+LABA+CsI- IFD-4

65,2

27,617,242

25,9

14,83,513,010,458

17,5

0,007

Pro

porc

ión

de p

acie

ntes

(%)

Nivel de gravedadI

0

25

50

75

100

Nivel de gravedadII

Nivel de gravedadIII-IV

n=223CONTROLBajo impacto: CAT≤10 puntosEstabilidad: Cambio CAT≤2 puntos

CONTROLCAT≤20 puntosCambio CAT≤2 puntos



Mal control

Pro

porc

ión

de p

acie

ntes

(%)

No agudizador

0

25

50

75

100

Agudizador con enfisema

Agudizador con bronquitis crónica

Fenotipomixto



Mal control

International Prospective Validation StudyMulticenter, international and prospective study to validate the concept of control in COPD and its implications for clinical practice

Protocol summary

HypothesisControl in COPD is a new conceptual dimension requiring demonstration of both low impact and clinical stability. The developers of the concept hypothesize that a status of control in COPD 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.

ObjectivesPrimary: to evaluate, in an international cohort of routine care/unselected COPD patients, the:• Levels of COPD control (vs poor COPD control), and• 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.

Design

21 months prospective pragmatic trial, comprising 5 evaluation points: one screening evaluation and 4 follow-up evaluations

3 months 6 months(9 months from screening visit)

6 months(15 months from screening visit)

6 months(21 months from screening visit)

Visit -1(Screening visit)

Visit 0(Baseline visit)

Visit 1(Follow-up visit)



Clinician-guided (“usual care”) treatment throughout the study

Screening assessment

Baselineassessment

Control 1

Control 2

Control 3

Visit Summary

Visit -1: Screening Visit (I)14. History of exacerbations in the last 12 months Number of exacerbations: Treated in the ambulatory setting Requiring visit to the Emergency Department and/or hospitalization

15. Symptoms

Visit -1: Screening Visit (I)

Demographic data:1. Date of Birth _______

2. Gender Man Woman

3. Living Status: Alone; In a couple; With relatives; In an institution; With carers

4. Level of Education: No studies; Primary school; Secondary School; Degree/College

5. Employment status: Working; Unemployed; Retired; Incapacity or permanent disability

6. Smoking status: – Former Smoker– Smoker: number of cigarettes per day & Years of smoking

7. Weight Kg

8. Height , m.

9. Charlson Comorbidity Index

Visit -1: Screening Visit (II)

COPD data:10. Year of diagnosis

11. COPD characteristics: Chronic Bronchitis; Emphysema; Asthma-COPD; Exacerbator; Overlap syndrome

12. Data of last spirometry (last 12 months)Pre-bronchodilatation valuesFVC ml % FEV1 ml % FEV1/FVC %

Post-bronchodilatation valuesFVC ml % FEV1 ml % FEV1/FVC %

KCO % TLC % RV %

Visit -1: Screening Visit (III)COPD data continued

13. Respiratory comorbidities (Yes / No)o Bronchiectasis; o Obstructive sleep apnea

14. History of exacerbations in the last 12 months Number of exacerbations: Treated in the ambulatory setting Requiring visit to the Emergency Department and/or hospitalization

15. Symptoms continued…

Sputum: Absent or white Dark Rescue medication in the last week: Average puffs per day: _____Days a week: ____ Total CAT scoreTotal CCQ score 16. Physical activityTime walked per day in minutes: ____ min.6 Minutes Walking Test: _________ m


16. TreatmentCheck Yes / No boxes:o SABAo SAMAo LABAo LAMAo ICSo Theophyllineo Macrolideso IPD4o LTOTo NIVo Influenza vaccineo Pneumonia vaccineo Respiratory rehabilitation

Others: ………………………………………………………..


Visits 0 & 1–3: Baseline & Follow-up (I)

1. Exacerbations since last visit Exacerbations treated in the ambulatory setting: _____ ; Date of first episode: __/__/__ Date of second episode: __/__/__ Exacerbations requiring visit to Emergency Department and/or hospitalization: _______Date of first episode: __/__/__ Date of second episode: __/__/__ 2. Symptoms

2. Symptoms continued…

Sputum: Absent or white Dark Rescue medication in the last week: Average puffs per day: _____Days a week: ____ Total CAT scoreTotal CCQ score 3. Physical activityTime walked per day in minutes: ____ min.

Visits 0 & 1–3: Baseline & Follow-up (II)

4. Treatment Changes Changes in treatments from the last visit (check Yes / No boxes)

SABA; SAMA; LABA; LAMA; ICS; Theophylline; Macrolides; IPD4; LTOT; NIV; Influenza vaccine; Pneumonia vaccine; Respiratory rehabilitation

Others: ………………………………………………………..

5. Continuation Status Continue in the study yes no

If no, please indicate the reason for discontinuation from: • Death: Respiratory; Cardiovascular; Cancer; Other • Withdrawal of consent • Lost to follow-up• Other

Visits 0 & 1–3: Baseline & Follow-up (III)

Eligibility CriteriaInclusion criteria: Eligible patients must meet the following inclusion criteria:• Spirometry-defined COPD (i.e. post-bronchodilator FEV1/FVC<0.7)• Age ≥40 years• Smokers or ex-smokers of at least 10 pack-years• In stable state (as judged by the investigator) at point of recruitment

Exclusion criteria: Patients will be excluded from the trial if any of the following are true, they:• Have any chronic concomitant respiratory condition other than asthma or

bronchiectasis (e.g. cystic fibrosis, lung fibrosis) • Have severe comorbidity with a life expectancy shorter than 2 years• Are unable to understand the instructions of the study or to fill the

questionnaires• Are unwilling to sign the informed consent• Are participating in another clinical study or clinical trial.

Endpoints: primary

Difference between patients controlled vs uncontrolled at baseline in (annualized) rates of the composite endpoint:• Unscheduled visits to the physician or emergency room

attendance for COPD• An exacerbation of COPD• All-cause: hospitalization or mortality

Endpoints: secondary• Difference between patients controlled vs uncontrolled at baseline in terms of:

o The (annualized) rate of exacerbations o Time to the first composite event o Time to the first exacerbations

• Comparison of CAT and CCQ as tools to identify impact and stability in COPD

• Distribution of control level across in those receiving guideline vs non-guideline recommended therapy (i.e. stratification of control across different treatment groups)

• Demographic and clinical characteristics associated with poor control of COPD

• Differences in utilities between patients controlled and uncontrolled (measured by the EQ-5D).

Recruitment

• Study power:o ≥285 patients are required to power the primary endpointo >285 patients may will permit subgroup analyses to be

conducted and give sufficient power to evaluated significant differences in some of the secondary endpoints

• Recruitment distribution:o To include ≥6 countrieso To recruit ~50 patients per countryo To achieve ~even distribution between national contributions

Participating Collaborators & CentresParticipating Collaborator Affiliation Country Recruiting Estimated # of

PatientsMarc Miravitlles Pneumology Department, Vall d' Hebron University

Hospital, Barcelona Spain Yes TBC

Juan José Soler-Cataluña Pneumology Department, Hospital Arnau de Vilanova, Valencia, Spain Spain Yes 50

Bernardino Alcazar Navarrete

Respiratory Department, Hospital de Alta Resolucion, Granada Spain Yes 75

Miguel Roman Rodriguez Institituto de Investigacíon Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain Spain (Mallorca) Yes TBC

David Price University of Aberdeen, Aberdeen UK Yes 250

Jennifer Quint University College Hospital, London UK No NA

David Halpin Department of Respiratory Medicine, Royal Devon & Exeter Hospital, Exeter UK Maybe NA

Dermot Ryan Honorary Fellow at the University of Edinburgh UK No NA

Alberto Papi S. Anna University Hospital, Ferrara Italy No TBC

Nicolas Roche* University of Paris Descartes, Paris France Yes 50

Richard Costello Royal College of Surgeons, Dublin Ireland Yes 50

Faisal Yunus Department of Pulmonology and Respiratory Medicine, Universitas Indonesia (FMUI), Jakarta Indonesia No NA

Helgo Magnussen Pulmonary Research Institute at Lung Clinic Grosshansdorf Germany No 0

Akio Niimi Department of Respiratory Medicine, Kyoto University Graduate School of Medicine Japan No 0

Jean Bourbeau Montreal Chest Institute, Montreal, Quebec Canada Yes TBC

Donald Sin University of British Columbia Canada Yes ≤50

Theresa Lapperre Singapore General Hospital Singapore Yes 50

Total ~600

Green indicates national coordinating centre; *2-3 active centres under Initiatives BPCO be included

Indicative Timelines

Next steps

• Ethics applications / requirements, by country• Organisational roles & responsibilities• Operational requirements

o Language translationso eCRF development

2015 ERS EVENTS

ICS CESSATION IN COPD: A REAL-LIFE STUDY Prof. Dr. Dirkje S. Postma Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, The Netherlands

Background (III)

• Studies seeking to address whether combination ICS/LABA therapy improves COPD stability have traditionally concluded that withdrawal of ICS therapy is associated with:1–3 o An increase in exacerbations and symptoms; o Reduction in health-related quality of life o An acceleration in lung function decline.

• Investigators have also concluded that ICS lack sustained disease-modifying effects after ICS cessation following a recent comparative study of lung function decline, AHR, and QOL over a 5-year follow-up period.4

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.

Background (III): WISDOM

• A recent large (n=2485) RCT evaluating the effect of gradual ICS withdrawal in COPD patients on triple therapy (ICS/tio/salmeterol) observed that:o Exacerbation rates were similar in patients continuing versus

discontinuing ICS therapyo No significant differences in outcomes between ICS withdrawal and

triple therapy patients across subgroups in which a greater degree of dependence on ICS might be expected

o No significant between group difference in the rate of dropout o However… a greater decrease in lung function decline was observed in

patients discontinuing ICS therapy in the final step of ICS withdrawal.

1. Magnussen H, et al. NEJM. 2014;371:1285-94.

Study Concept

• The aim of the study is to 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.

Design: overviewUsing electronic primary care records data from the UK’s Optimum Patient Care Research Database (OPCRD), the study will include 3 x 2-way matched analysis:

Patient PopulationInclusion criteria• Have a COPD diagnosis:

o Physician-diagnosed COPD (presence of a COPD Read code); and/oro Spirometry-defined COPD: post-bronchodilator FEV1/FVC<0.7

• Aged ≥40 years• Current or ex-smokers• Have ≥2 years’ of continuous patient records

o Have ≥1 years’ of continuous patient records prior to index date (baseline) o Have ≥2 years’ of continuous patient records post index date (outcome)

• Be on active ICS/LABA or ICS/LABA/LAMA therapy (receive prescriptions covering ≥6 of the 12 months) in the baseline year

• ≥1 year of continuous clinical records immediately following the index date.

Exclusion criteria• Patients with any other chronic respiratory condition will be excluded from

the analysis

Cohort A: ICS Cessation

• Rationale: conscious clinical decision to stop ICS therapy by issuing no further ICS prescriptions (but continuing bronchodilator therapy) for a period of at least 12 months.

• Index date: date at which patient receive their first LABA or LABA/LAMA prescription following a prior ICS/LABA or ICS/LABA/LAMA therapy

• Outcome period: 12-month primary outcome period, outcomes will also be evaluated at 121 weeks (3 months) and at annual intervals 1 year (primary endpoint), 2, 3, 4 and 5years2 (exploratory endpoints) following index date.

• Additional inclusion criteria: received ≥3 ICS-containing prescriptions during the 6 months immediately prior to index date

1. Kunz LI, et al. Chest. 2015;148:389-96. 2. Magnussen H, et al. NEJM. 2014;371:1285-94.

Cohort B: ICS Reduction (prescribed)

• Rationale / clinical inference: conscious clinical decision to reduce ICS exposure by lowering prior ICS dose.

• Index date: date at which patient receive their ICS or ICS/LABA at ≥50% lower prescribed dose• Outcome period: annual intervals 1 year (primary endpoint), 2, 3, 4 and 5 years (exploratory

end points) following index date• Additional inclusion criteria: Patient must receive ≥2 ICS-containing prescriptions at index

date dose in the 1-year primary outcome period (and each of the consecutive one-year evaluation periods).

Cohort C: ICS Reduction (“consumed”)

• Rationale / clinical inference: reduction in ICS exposure (i.e. absolute number of prescriptions) evidenced by a reduction in ICS medication possession ratio (implying a patient-driven reduction in use / repeat prescription activity)

• Baseline: 1-year immediately prior to index date• Outcome period: 1-year immediately following index date• Index date: date where after a ≥50% reduction in ICS MPR over the following 12 months is

observed compared to baseline ICS MPR.

EndpointsOutcome period:• 1 year (primary) and at annual intervals thereafter out to 5 years.1

• To reflect the 12-week outcome period used by in WISDOM the endpoints (where evaluable) will be censored at 12 weeks.2

Co-primary endpoints• Change in FEV1 (FEV1)**“Baseline FEV1”: measurement closest to index date; valid measures must not precede index date by more than 24 months. “Outcome FEV1”: valid measures must be recorded within 3 months of the intended outcome date (i.e. for FEV1 at 1 year,

data must be recorded within the 9–15 months post index date)

Secondary endpoints• Time to first moderate/severe COPD exacerbation:• Exacerbation rate over the 1-year outcome period• COPD-related hospitalisations• Time to first COPD-related hospitalisation1. Magnussen H, et al. NEJM. 2014;371:1285-94;

2. Kunz LI, et al. Chest. 2015;148:389-96.

Interaction analysisThe interaction between the follow patient / clinical features and the study outcomes will be explored:• Number of baseline exacerbations• Comorbid baseline respiratory therapy:• Comorbid asthma• Current vs ex-smoking status• Blood eosinophil level (i.e. presence of eosinophilia) • Prescribed baseline ICS particle size (extra-fine vs non-

extrafine)

Feasibility: OPCRD Patient NumbersCOPD patients NumberCOPD diagnosis ever 132,962

On Triple Therapy (≥1 prescription for ICS, LAMA and LABA in latest 12-month period)

25,987

On triple therapy and discontinue ICS *(on prescription of ICS, LABA and LAMA in baseline with only LABA and LAMA in outcome (using any LABA/LAMA prescription as index date)

687

On triple therapy and discontinue ICS* with ≥1 FEV1 during baseline year and FEV1 reading in the 0-5 years following ICS cessation/reduction

356

reg copd control working group meeting 25/9/15

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