2018 EULAR recommendations for a core data set to support observational research and - PowerPoint Presentation

Slide1

2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis

Aim

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05/11/2018

Giant cell arteritis (GCA): most common primary systemic vasculitis in western countriesLifetime risk: 1.0% for women and 0.5% for men over the age of 50 yearsSevere potential complications: sight loss, stroke, cranial nerve palsy, large-vessel aneurysms, vascular stenosesNew therapeutic approachesRecent approval of tocilizumab for GCA treatmentNovel therapies currently investigated: inhibition of IL-1beta, T cell co-stimulation, Janus kinases 1/2Unanswered questions regarding disease outcome, co-morbidities, and treatment courseData lag behind what is available for other rheumatic diseases like rheumatoid arthritisEstablishing national and supranational registries would enable the systematic collection of important data on demographics and diagnostic and therapeutic approaches and thereby improve clinical care

Rationale

Aim

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05/11/2018

Develop a minimum core set of parameters collected for newly and previously diagnosed patients with GCAEnsure that data from different registries and databases are standardised Facilitate collaborative analysesStandardised core set to be usedin national and supra-national registriesfor post-marketing surveillance purposesin creating an international cohort of GCA patients to support initiatives of individual researchersUltimately increase the quality of GCA data collection and care in clinical practice and research

Objective

Task force members

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05/11/2018

1

Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany; 2 Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; 3 Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, Netherlands; 4 Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; 5 Research Laboratory & Academic Division of Clinical Rheumatology, Dept. of Internal Medicine, IRCCS Polyclinic San Martino, University of Genoa, Italy; 6 Southend University Hospital NHS Foundation Trust, Westcliff-on-Sea, Essex, UK; 7 Department of Rheumatology, Medical University Graz, Graz, Austria and Rheumatology Service, Hospital of Bruneck, South Tyrol Health Trust, Italy; 8 Arthritis Research UK Centre for Epidemiology, School of Biological Sciences, University of Manchester, Manchester, UK; 9 Medical Products Agency, Uppsala, Sweden, and Cross-Committee Task Force on Registries at the European Medicines Agency, London, UK; 10 Division of Rheumatology, Geneva University Hospital, Geneva, Switzerland; 11 Patient Representative from PMRGCAuk; 12 Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; 13 Department of Internal Medicine, Hospital Saint-Louis, University Paris Diderot, Paris, France; 14 Division of Rheumatology and Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA; 15 Patient Representative from PMR-GCA Scotland; 16 Division of Rheumatology, Azienda USL–Istituto di Ricovero e Cura a Carattere Scientifico di Reggio Emilia, Reggio Emilia, Italy; 17 Università di Modena e Reggio Emilia, Modena, Italy; 18 Immanuel Krankenhaus Berlin: Medical Center for Rheumatology Berlin-Buch, Berlin, Germany; 19 Epidemiology Unit, German rheumatism research Centre, DRFZ Berlin, Berlin, Germany; 20 Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, Netherlands

Lisa Ehlers1Johan Askling2Johannes W. J. Bijlsma3Maria C. Cid4Maurizio Cutolo5 Bhaskar Dasgupta6 Christian Dejaco7 William G. Dixon8 Nils Feltelius9 Axel Finckh10 Kate Gilbert11 Sarah Mackie12 Alfred Mahr13 Eric L. Matteson14 Lorna Neill15 Carlo Salvarani16,17 Wolfgang A. Schmidt18 Anja Strangfeld19 Ronald van Vollenhoven20Frank Buttgereit1

Methodological approach

Task force members

5

05/11/2018

expertise

16 countries

rheumatologists

internal

medicine

specialistsepidemiologistsEMA representativepatient representativesrheumatology fellow

Methodological approach

Consensus process

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05/11/2018

Breakout

group discussionsRefinement of candidate itemsDevelopment of a framework for the core set of items

Item

compilation

Literature

review

Parameter collection and allocation to domains

Task

force meeting

Item

refinement and prioritisation

Consensus and level of agreement

Email discussions

Three-round Delphi survey

66

items

117

items

50

items

Methodological approach

Consensus process

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05/11/2018

Core

items

see

below

Night

sweats

Laboratory

Leukocytes

, thrombocytes, erythrocytes, fibrinogenLarge vessel involvement Bruits, PET activityComorbidities & adverse events Congestive heart failure, gastrointestinal perforation, latent tuberculosis

General Examiner, ethnicity, heart rateGCA-related Scalp necrosis, tongue claudication, dry cough, limb claudication, peripheral arthritis/bursitis, distal extremity swelling with pitting edema, health-related function, health- related quality of life, fatigueComorbidities & adverse events Allergic drug reaction, complication during diagnostic/therapeutic procedure, hemiplegia, DVT, PAD, dyslipidaemia, Cushing, gastric/duodenal ulcers, diverticulitis, chronic liver disease, infection (HBV, HCV, HIV, VZV), Depression, insomnia, mood changes, dementia, cataract, glaucoma, COPD, asthma, ILD, CKDMedication Current GC tapering, cumulative GC dosage

Items excluded during final voting procedure

Excluded items considered important, but not obligatory

Excluded items considered relevant for the creation of a GCA registry

General Menopause, number of pregnancies/births GCA-related Pain related to GCA, ROM proximal muscles, malaise, hearing loss Comorbidities & adverse events Alcohol/drug abuse, chronic bacterial infections Blood glucose, sodium, potassium Medication Bisphosphonates, PPI, ACE inhibitors/ARB, statins, anticoagulants

Core

items

see below

Methodological approach

Results

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Core set of parameters informed by the trade-off between what is scientifically desirable and what is clinically feasibleComprehensive dataset that can be collected in routine clinical careItems facilitate the assessment of theoutcome and prognosis in subgroups of patients with GCAeffectiveness of instruments to diagnose and monitor GCAeffectiveness and safety of different therapeutic approaches Ensure comparability of data collected in different registriesParameters can individually be added to meet the specific needs of the respective registry or database

Overarching principles

Results

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Minimum core set of parameters to be collected in giant cell arteritis registries and databases

Item

Instrument

Baseline

Follow-

up

General

patient identifier

x

x

visit

date

date

x

x

Demographics

age

date of birth

(convert to

year of birth

for anonymization)

x

sex

male/female

x

weight

2

kg (measure)

x

x

height

4

cm (measure)

x

x

smoking

2

no/past/current, pack-years: ______

x

x

GCA diagnosis

ICD-10 code (M31.5 / M31.6)

x

date of GCA diagnosis

date (medically reported diagnosis)

x

onset

of

symptoms

date (interview)

x

Results

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Minimum core set of parameters to be collected in giant cell arteritis registries and databases

Item

Instrument

Baseline

Follow-

up

GCA-related signs & symptoms

cranial

2

ocular

involvement

ocular symptoms: diplopia, blurring, transient visual loss (

amaurosis

fugax

)

y/n (interview)

x

x

permanent partial visual loss / field defect / blindness / RAPD

y/n (examination), if yes: AION/CRAO/other

x

x

headache

y/n (interview)

x

x

scalp tenderness

y/n (interview)

x

x

jaw claudication

y/n (interview)

x

x

cranial artery abnormality

cord-like thickening / nodularity / tenderness / reduced pulse and/or pulselessness

y/n (examination)

x

x

sonographic evidence of arteritis

3

not assessed/y/n (ultrasound)

x

x

histological arteritis

not assessed/y/n, anatomical region, date of biopsy

x

constitutional: fever/pyrexia symptoms

2

y/n (interview)

x

x

laboratory

2

ESR

mm/h (1

st

h)

x

x

CRP

e.g. in mg/dL

x

x

haemoglobin

e.g. in g/dL

x

x

PMR

2

(inflammatory bilateral

shoulder/hip

pain

and stiffness)

y/n (interview/examination)

x

x

Results

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Minimum core set of parameters to be collected in giant cell arteritis registries and databases

Item

Instrument

Baseline

Follow-

up

GCA-related signs & symptoms

large vessel involvement

2

peripheral pulses (carotid, axillary, brachial, radial, femoral): pulsation

y/n (examination)

x

x

blood pressure

mmHg (left & right arm)

x

x

dilatation/aneurysm

not assessed /y/n

5

, vessels involved:

___________

x

x

wall thickening

3

not assessed /y/n

5

, vessels involved:

___________

x

x

stenosis

3

not assessed /y/n

5

, vessels involved:

___________

x

x

disease activity

2

patient’s global assessment of disease activity

NRS scale capturing global assessment of disease activity

attributable to GCA

and

today

x

x

evaluator’s global assessment of disease activity

NRS scale capturing global assessment of disease activity

attributable to GCA

and

today

x

x

Results

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Minimum core set of parameters to be collected in giant cell arteritis registries and databases

Item

Instrument

Baseline

Follow-

up

Other medical events or conditions

7

death

1

if yes: cause:______________

x

cardiovascular

TIA

1

date

5

,



evidence of

vasculitic

change of supplying arteries

x

x

stroke

1

ischaemic

date

5

,



evidence of vasculitic change of supplying arteries

x

x

haemorrhagic

date

5

,



evidence of vasculitic change of supplying arteries

x

x

myocardial infarction

1

Date

x

x

arterial hypertension requiring treatment

2

yes

6

/no

x

x

endocrine

diabetes mellitus

2

yes

6

/no

x

x

osteoporosis

8

yes

6

/no



radiological evidence of a fragility fracture



BMD: ________ (date) (DXA or

qCT

not older

than

12

months)

x

x

infection

1

active tuberculosis

yes

6

/no

x

x

serious

infection requiring

hospitalisation

date, type: ___________

x

x

malignancy

1

haematopoietic

date, type:

___________

x

x

solid

tumour

date, type:

___________

x

x

skin

date, type:

___________

x

x

other serious event

1

date, specify:_________

x

x

Results

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05/11/2018

Minimum core set of parameters to be collected in giant cell arteritis registries and databases

Item

InstrumentBaselineFollow-upTreatment2   glucocorticoids   current usemg per day in prednisone equivalent, route of administrationxxrecent usecontinuous (> 3 months) intake: y/n (interview)xximmunosuppressants/-modulators    conventional synthetic DMARDscurrent medication9xx historical treatment10x biological DMARDscurrent medication9 xxhistorical treatment10x targeted synthetic DMARDscurrent medication9 xxhistorical treatment10x antiplatelet agentscurrent medication9xxhistorical APT10x 

1

report with date if it occurs

2

record every 3-6 months; clinically relevant changes/events need to be recorded whenever they occur (e.g. new medication, imaging finding, osteoporotic fracture)

3

record every 6-12 months; clinically relevant changes/events need to be recorded whenever they occur (e.g. new medication, imaging finding, osteoporotic fracture)

4

record annually; clinically relevant changes/events need to be recorded whenever they occur (e.g. new medication, imaging finding, osteoporotic fracture)

5

record whether the item was assessed by CT / PET-CT / US / MR

6

if yes, record: date of first diagnosis, indicate if worsened since the last visit

7

unless otherwise indicated, items are to be assessed with the help of information reliably provided during the patient interview or clinical records if

available

8

perform testing if indicated

9

collect the following information: drug (generic name), start date, dose, route of administration;

if applicable:

stop date, stop reason (inefficacy /

AE

/ both / other)

10

only applicable for patients with existing disease at baseline: list previous drugs (generic name

)

Results

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05/11/2018

Level of agreement

Item

LoA*General patient identifier9,85 ± 0,49 [8;10] (100%)visit date9,90 ± 0,31 [9;10] (100%)Demographics age9,95 ± 0,23 [9;10] (95%)sex9,95 ± 0,22 [9;10] (100%)weight8,65 ± 1,42 [5;10] (95%)height8,50 ± 1,36 [5;10] (95%)smoking9,25 ± 0,91 [8;10] (100%)GCA diagnosis9,60 ± 0,75 [8;10] (100%)date of GCA diagnosis9,60 ± 0,82 [8;10] (100%)onset of symptoms8,95 ± 1,73 [3;10] (95%)GCA-related signs & symptoms cranial ocular involvement ocular symptoms: diplopia, blurring, transient visual loss (amaurosis fugax)9,25 ± 1,48 [4;10] (95%)permanent partial visual loss / field defect / blindness / RAPD9,20 ± 1,36 [5;10] (95%)headache9,05 ± 1,88 [2;10] (95%)scalp tenderness8,45 ± 2,14 [1;10] (90%)jaw claudication8,40 ± 2,21 [1;10] (90%)cranial artery abnormality cord-like thickening / nodularity / tenderness / reduced pulse and/or pulselessness8,35 ± 2,56 [0;10] (85%)sonographic evidence of arteritis8,30 ± 2,64 [0;10] (80%)histological arteritis8,84 ± 2,54 [0;10] (85%)constitutional: fever/pyrexia symptoms8,10 ± 2,20 [3;10] (75%)laboratory ESR9,10 ± 1,29 [6;10] (95%)CRP9,55 ± 0,94 [7;10] (100%)haemoglobin7,50 ± 2,59 [0;10] (75%)PMR (inflammatory bilateral shoulder/hip pain and stiffness)9,45 ± 0,94 [7;10] (100%)large vessel involvement peripheral pulses (carotid, axillary, brachial, radial, femoral): pulsation8,10 ± 2,34 [2;10] (70%)blood pressure7,90 ± 2,15 [1;10] (80%)dilatation/aneurysm7,79 ± 3,05 [0;10] (75%)wall thickening7,15 ± 3,17 [0;10] (65%)stenosis7,50 ± 3,00 [0;10] (75%)disease activity patient’s global assessment of disease activity8,70 ± 2,27 [1;10] (90%)evaluator’s global assessment of disease activity8,55 ± 2,50 [0;10] (85%)

ItemLoA*Other medical events or conditions death9,70 ± 0,73 [8;10] (100%)cardiovascular TIA8,70 ± 1,84 [3;10] (90%)stroke ischaemic8,84 ± 2,14 [2;10] (85%)haemorrhagic8,10 ± 2,25 [1;10] (85%)myocardial infarction8,42 ± 2,12 [1;10] (90%)arterial hypertension requiring treatment8,45 ± 2,35 [0;10] (90%)endocrine diabetes mellitus8,70 ± 1,69 [4;10] (90%)osteoporosis8,60 ± 1,43 [5;10] (90%)infection active tuberculosis8,00 ± 2,03 [4;10] (75%)serious infection requiring hospitalisation9,00 ± 1,12 [7;10] (100%)malignancy haematopoietic9,05 ± 1,05 [7;10] (100%)solid tumour 9,05 ± 1,05 [7;10] (100%)skin 7,95 ± 1,85 [4;10] (85%)other serious event8,15 ± 2,01 [3;10] (75%)Treatment glucocorticoids current use9,80 ± 0,52 [8;10] (100%)recent use9,75 ± 0,55 [8;10] (100%)immunosuppressants/-modulators conventional synthetic DMARDs9,75 ± 0,55 [8;10] (100%)biological DMARDs9,90 ± 0,31 [9;10] (100%)targeted synthetic DMARDs9,80 ± 0,41 [9;10] (100%)antiplatelet agents9,15 ± 0,93 [7;10] (100%) 

* Level of agreement

was based on an anonymized survey with a 0-10 scale by all members of the task force (data are mean

± standard

deviation [minimum; maximum rating] and in brackets the percentage of task force members with an agreement ≥ 7

))

Summary

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05/11/2018

2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis

This EULAR task force proposes a minimum core set of 50 parameters, subdivided into the following categories: General, Demographics, GCA-related signs and symptoms, Other medical conditions, and Treatment.

Each item achieved a level of agreement of at least 7 in a group of experts in the field of rheumatology and epidemiology supported by patient research partners.

The dataset represents a compromise derived from high scientific interest conflicting with feasibility in clinical routine care.

The implementation of this core set in existing and evolving GCA registries will ensure

harmanised

data exchange and increase the quality of GCA data collection.

The ultimate goal of these recommendations is to enhance collaboration and comparability and eventually improve GCA research and clinical care.

Summary

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05/11/2018

2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis

Recommendation

A minimum of 50 items should

be collected in giant cell arteritis registries and databases.

These items represent parameters

routinely collected in clinical practice.

By implementing

our recommendations practitioners and patients make a significant contribution to the improvement of research and clinical care in the field of giant cell arteritis.

Standardised

data

collection

ensures

comparibility

and

thereby

enlarges

the

amount

of

information

available

for

future

research

.

The

proposed

set

of

items

can

be

extended

depending

on

the

intended

investigation

.

Acknowledgements

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05/11/2018

Funding

We

thank

EULAR

for

financially

supporting

the

activities

of

this

task

force

.

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icons

used

in

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