IPF/ILD Working Group Meeting ERS 2017 Milan, 9th September 2017

Agenda Working group progress update Priorities for future research ILD-MDT phase II Priorities for future research Research ideas Relevant, feasible, valid and a priority Setting priorities Additional items

Attendees Kevin Flaherty (chair) A Azuma P Rottoli V Cottin J Behr A Niimi F Luppi S Andarini C Youakim P Rivera Ortega

Progress update Published studies Martinez FJ, Chisholm A, Collard H R, et al 2017. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Resp Med: 5 (1), 61-71

Active study update (1) REG-RES1510: Characterisation of the path to idiopathic pulmonary fibrosis (IPF) and potential missed diagnostic opportunities Presented at Working Group meeting at ERS 2016 Final report complete December 2016

Study Aims With a view to identifying potential opportunities for earlier referral to specialists and (ultimately) earlier diagnosis of IPF, the study aims to: Characterise the clinical features of patients at the time of their IPF diagnosis Evaluate patients’ patterns of HRU in the years preceding their IPF diagnosis Develop optimum code lists for IPF database research, i.e. variation in 1 & 2 for sensitive versus specific code lists

Methods Inclusion criteria A diagnostic Read code for IPF Diagnosed with IPF between 1990 and 2015. A minimum of 2 years continuous clinical records in the years immediately preceding their index diagnosis Aged 40 years or older at index date

Clinical features of patients at the time of their IPF diagnosis In this routine care IPF population from the UK: Demographics Mean age: 72-73 years Men accounted for 62-65% of the population Approximately 1/3 were never smokers; 2/3 current or ex-smokers Comorbidities 13-25% had obstructive lung disease (13-15% asthma; 19-25% COPD) Approximately 50% of patients: Had cardiovascular disease (46-53%) Consulted for cough (40-52%; ~10% in the 2 years preceding IPF diagnosis) Respiratory therapies 18-26% of patients received ≥1 prescription for SABA in the year preceding IPF diagnosis Prescribing of all other obstructive lung disease therapies (ICS, LABA, LAMA, combinations) was low (<10%)

Patterns of HRU in the years preceding their IPF diagnosis All markers of respiratory health resource use (HRU) increased annually over the 10-years and quarterly within the last 2 years leading up to patient’s IPF diagnosis: Primary care events LR consultations, LR antibiotics and oral steroids (acute and maintenance) Secondary care attendances Hospital admissions, Out patient department attendances, Accident & emergency attendances Other: Cough events, Chest X-rays, Incidence of pneumonia

Code lists: specific vs broad Compared with patients with a “specific” IPF diagnostic code, those with a “broad” diagnostic label were similar in terms of their: Demographic presentation at the time of diagnosis Escalating trends in HRU in the years preceding IPF diagnosis Lung function: Similar mean(SD) FVC: 3.1(6.8) vs. 2.5(0.9) (p=0.405) Comorbidities broad IPF patients had: Similar burden of: Chronic respiratory conditions (incl. asthma; excl COPD); heart failure, rhinitis, bronchiectasis, eczema, osteoporosis, cerebrovascular disease, sleep apnoea, depression and anxiety Higher burden of : COPD, cardiovascular disease, ischaemic heart disease, Hypertension, diabetes, myocardial infraction, GERD,CKD, lung cancer, cough Drug usage: broad IPF patients had higher use of short-acting bronchodilator therapy in the year preceding IPF diagnosis (26 vs 18%)

Next steps Final report has been published No control group Write up without control group or secure funding to conduct supplementary study with controls? Potential to publish comparison of specific vs. broad IPF definitions

Active study update (2) REG-RES1505: Characterisation of interstitial lung disease (ILD) diagnostic practice around the world and implications on diagnostic agreement and access to licensed therapies Phase I: Presented at REG summit 2017 and ATS 2017 Final report out for comments Poster presentation: 12.50pm-2pm on 12th September Phase II: Protocol under development

Centre type by economic status* 570 responses, of which 457 were unique and valid Very few low or lower middle income countries. The effects of income on practice are therefore hard to determine. All centres in low income countries are academic ILD centres. Questions: Do you work in an academic or university medical centre? Do you work at an ILD centre? Centre Type High Income, n (%) Upper middle income, n(%) Lower middle income, n(%) Low income, n(%) ILD Academic Centre 148 (48.4) 49 (40.2) 6 (22.2) 2 (100) Non-ILD Academic Centre 83 (27.1) 42 (34.4) 8 (29.6) 0 (0.0) Non Academic Centre 75 (24.5) 31 (25.4) 13 (48.1) TOTAL 306 122 27 2 *Economic status: World Bank List of Economies, March 2017

Caseload of centre Academic ILD centres reported a higher caseloads of both IPF-ILD and non-IPF ILD than academic non-ILD or non-academic centres (Kruskal Wallis: p<0.001) Caseload characteristic ILD Academic Centre (n=205) Non-ILD Academic Centre (n=133) Non Academic Centre (n=119) All Centres (n=457) IPF ILD cases/ month Median(IQR) 5.0(3.0-10.0) 4.0(2.0-5.0) 3.0(2.0-5.0) 4.0(2.0-7.0) Range 0-50 0-35 Non-IPF ILD cases / month 16.0(10.0-27.0) 10.0(5.0-20.0) 10.0(5.0-15.0) 11.0(6.0-20.0) 1-130 1-101 0-200 Questions: Approximately how many new cases/referrals of IPF does your centre diagnose in an average month? Approximately how many new cases/referrals of IPF does your centre diagnose in an average month? Mean has been taken out as data were massively skewed – so median is the better presentable number Where, box=25th percentile, median and 75th percentile; whiskers= values within 1.5 interquartile ranges of the 25th and 75th percentile.

Diagnostic meetings Characteristics of formal meetings

Access to anti-fibrotic agents Questions: Do you have access to the anti-fibrotic agents nintedanib and/or pirfenidone at your centre? Is the MDT permission required to access nintedanib and/or pirfenidone? Anti-fibrotic agents were available to 81.4% (n=372) of centres, of which 31.7% (n=118) required the permission of a multi-disciplinary team to access them. Access was more frequently reported in academic ILD centres (n=180, 87.8%) than academic non-ILD (100, 75.2%) or non-academic centres (92, 77.3%). Neither of the two centres in low income countries had access to anti-fibrotics.

Conclusions While there were some differences in practice based on the centre type, region of the world or the economic status of the country the centre was located in, practice was broadly similar.

Next steps: Phase II Proposed methodology Objective Evaluate agreement of ILD MDT diagnosis across a range of global sites and healthcare settings Evaluate accuracy of ILD MDT diagnosis across a range of global sites and healthcare settings, considering in particular agreement in IPF diagnosis Identify features of current MDT diagnostic practice associated with accurate diagnosis (including the effect of bronchoscopic sampling for diagnosis) Produce a series of recommendations as to how best to optimise the pathway to accurate ILD diagnosis in real-world practice. Design: Digitised reference ILD cases (including pathology data) will be presented to participating centres. Outcomes: Descriptive analysis of participating MDTs and MDT diagnostic accuracy. Concordance across centres, and between reported practice (phase I) and observed practice (phase II). Analysis of independent MDT features associated with diagnostic accuracy. Recommendations associated with optimising the diagnostic process

Next steps: Phase II questions How will cases be digitised, what platform, what prompts/questions What cases Source of cases and case-mix Which centres 464 individuals from 394 (86.2%) centres in phase I stated the would be happy to participate in phase II MDT definition How should we define an MDT?

Active study update (3) REG_P040: Characterise the natural history of IPF vs non-IPF ILD in terms of FVC lung function decline Final report written Results presented at REG summit 2017 A manuscript may be in development?

Study Design Electronic medical records from both the Optimum Patient Care Research Database (OPCRD) and the Clinical Practice Research Datalink (CPRD) Inclusion criteria: Received their IPF diagnosis between 1991 and 2016 Have a minimum of: 12 months of continuous clinical records immediately preceding index date 6 months’ continuous records immediately following index date Aged 40 years or older at index date Exclusion criteria: None

Health Care Utilisation (I)

Health Care Utilisation (II)

Mortality

Conclusions Individuals diagnosed with diseases compatible with ILD have very similar demographic and clinical characterizes at the time of or before diagnosis when compared to with those with IPF only A consistent increase in the use of healthcare resources 2-3 years prior to diagnosis was observed in all 4 cohorts

Future research Phase II of the ILD-MDT project Is there another, smaller, project that could run at the same time? Relevant? Feasible? Valid? A priority? How do we set priorities in IPF/ILD research? How to we ensure these priorities are pursued?

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