Cross-sectional, Multicentre, Non-interventional Study to Assess Giant Cell Arteritis Medical Practices in France
Conditions: Giant Cell Arteritis
Sponsor: Chugai Pharma France

CHUGAI PHARMA FRANCE 
 
 
 
 
 
Cross-sectional, multicentre, non-interventional study to assess 
Giant Cell Arteritis medical practices in France 
  
Artemis Study 
 
 
Protocol  
 
ID-RCB number: 2018-A00841-54 
 
Version 1.3 du 17.09.2018  
 
 
SPONSOR 
 
 
CHUGAI PHARMA FRANCE 
Tour Franklin - Arche Sud  
100/101 quartier Boieldieu 
92042 Paris La Défense cedex 
 
 
 
Tel: 
+33 1 56 37 05 20 
 
Fax: 
+33 1 56 37 05 40 
 
 
 
STUDY MANAGER 
 
Dr Isabelle IDIER 
Senior Medical Manager   
 
 
 
 
Tel: 
+33 1 56 37 44 89 
 
Mobile: +33 6 24 55 62 00 
 
Fax: 
+33 1 56 37 05 40 
 
 
 
CRO (monitoring, data processing, statistical analysis and medical writing) 
ITEC Services 
ZI Jean ZAY 
3, avenue Georges Clémenceau   
33150 CENON  
FRANCE 
Tel: 
+33 5 57 77 85 00 
Fax: 
+33 5 57 77 85 01 
 
 
 

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SPONSOR SIGNATORIES OF THE PROTOCOL 
 
The signatories attest that the Protocol Version 1.2 dated 20/06/2018, the CRF and appendices 
contain the information and recommendations required for the conduct of the study. The study 
will be carried out and recorded in accordance with this Protocol and Good Epidemiological 
Practice. Any amendment to the Protocol will require agreement from the signatories and will 
be documented in writing.  
 
 
SPONSOR 
Dr Thierry GUILLOT 
 
CHUGAI PHARMA FRANCE 
Tour Franklin - Arche Sud  
100/101 quartier Boieldieu 
92042 Paris La Défense cedex 
Date: ______________________________ 
 
 
Signature: __________________________ 
 
 
 
 
 
 
STUDY MANAGER 
Dr Isabelle IDIER 
CHUGAI PHARMA FRANCE 
Tour Franklin - Arche Sud  
100/101 quartier Boieldieu 
92042 Paris La Défense cedex 
 
 
Date: 
 
 
Signature: __________________________ 
 
 
 
 
 
 
 
 
 

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SCIENTIFIC COMMITTEE 
 
Pr Valerie Devauchelle-Pensec  
Rheumatology Department 
CHU LA CAVALE BLANCHE,  
Boulevard Tanguy Prigent  
29609 BREST CEDEX 2 
FRANCE 
Email : valerie.devauchelle-pensec@chu-brest.fr 
 
Pr Eric Hachulla  
Internal Medicine Department 
CHRU LILLE,  
2 Avenue Oscar Lambret 
59000 LILLE 
FRANCE 
Email : Eric.HACHULLA@CHRU-LILLE.FR 
 
 
Pr Alfred Mahr  
(Coordinator Investigator) 
Internal Medicine Department 
HOPITAL SAINT LOUIS,  
1 Avenue Claude Vellefaux 
75010 PARIS 
FRANCE 
Email : alfred.mahr@aphp.fr 
 
 
 
Pr Marc Paccalin  
Internal Medicine and Geriatic Medicine Department  
CHU LA MILETRIE,  
2 Rue de la Miletrie  
86021 POITIERS CEDEX 
FRANCE 
Email : Marc.PACCALIN@chu-poitiers.fr 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SUMMARY  
 
Study title 
Cross-sectional, multicentre, non-interventional study to assess Giant Cell 
Arteritis medical practices in France 
Population 
Patients with giant cell arteritis (GCA)  
Study rationale 
GCA - also known as temporal arteritis, cranial arteritis, or Horton’s disease - is a 
form of immune-mediated inflammatory systemic vasculitis that affects large and 
medium-sized arteries, predominantly affecting the extracranial branches of the 
carotid arteries and the subclavian and axillary branches of the aorta. GCA may 
present with systemic symptoms such as fever, but the most common symptom 
is temporal and occipital headache accompanied by scalp tenderness. The 
arterial blockage associated with GCA leads to ischemic symptoms such as jaw 
claudication, intermittent claudication of the tongue and muscles involved in 
swallowing, and rarely infarction of the scalp or the tongue. GCA causes 
significant complications, particularly vision loss (4% for patients with large-vessel 
GCA and 11% for those with cranial disease). 
There are currently few real-world data available in France on the management 
of patients with GCA and on their treatment sequences. 
We propose to conduct an observational study aiming to describe GCA 
management and patient characteristics in France. 
Study objectives 
 
Primary objective 
The primary objective is to describe medical practices in patients with GCA in 
terms of patient journey, diagnostic methods and specific GCA treatments since 
diagnosis. 
 
Secondary objectives 
 To describe comorbidities related to glucocorticoids (GCs) and associated 
treatments 
 To describe GCA characteristics in terms of GCA duration, initial presentation, 
clinical form and GCA activity 
 To describe the health status of GCA patients 
 To describe physician and patient characteristics 
 

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Study 
methodology 
 
Cross-sectional, non-interventional, national (France), multicentre study, 
conducted on a population of 300 patients with GCA, to describe GCA 
management and patient characteristics. 
The information will be collected during a single visit to the internist or 
rheumatologist as part of the usual management of the patient with GCA. The 
physician will not perform any additional examinations specific to the study. The 
physician will inform the patient about the study before inclusion and seek her/his 
non-opposition. A patient information form will be given to each patient by the 
physician. Patients who are eligible to take part in the study and who verbally 
agree to their data undergoing automated processing, will be included in the 
study.  
Data will be collected from the medical file and from patient questionnaires on 
health status (SF-36 [36-Item Short Form Survey Instrument], EQ5D [EuroQol-5 
Dimensions]) and fatigue (FACIT-fatigue). In addition, GCA activity will be 
evaluated using a global arteritis activity Visual Analog Scale (VAS) to be 
completed by the patient and the physician (Figure 1).  
The study will be conducted in accordance with the professional code of ethics 
and the good epidemiological practice guidelines developed by the Association 
of French-Speaking Epidemiologists) (ADELF; 2017). 
Figure 1 Study design 
 

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Number of 
physicians and 
method used to 
select them  
  
A national data base provided by an independent company (CEGEDIM) including 
approximately 2600 internists and rheumatologists practicing in hospitals or 
private clinics in Metropolitan France will be used to recruit 150 active (i.e. 
inclusion of at least 1 patient) physicians for the study. Each physician will have 
a specific site number. 
Physician will be selected by the Sponsor following rules and recommendations 
on relations between industry and health professionals. 
Number of 
patients and 
method used to 
select them 
It is expected that 300 patients (incident cases, i.e. newly diagnosed or prevalent) 
will be recruited in this study. Based on a previous study on GCA patients 
(database analysis of the Echantillon Généraliste des Bénéficiaires), there are 
2300 incident patients/year in France. Therefore, 300 incident and prevalent 
patients during the recruitment period seems realistic. 
Physicians will start patient inclusion only when the study is initiated at their site 
and when all regulatory authorisations are obtained. 
Each physician will be requested to include consecutively during the inclusion 
period, all the patients meeting the eligibility criteria listed below and accepting to 
participate in the study. In order to avoid any over-representation of a particular 
site or hospital, a maximum of 10 patients per hospital department will be able to 
participate in the study.  
 
Patient selection 
criteria 
 
Inclusion criteria 
Patients must meet the following criteria to be included in the study:  
 At least 50 years old.  
 Suffering from GCA as per investigator judgement, newly diagnosed or not.  
 Starting or under treatment for GCA.  
 Informed verbally and in writing about this study and not objecting to their data 
being electronically processed or subjected to data quality control. 
 
Non-inclusion criteria 
The patients fulfilling the following criteria cannot be included in the study:  
 Unable to consent  
 Participation to a randomised controlled clinical trial 
 

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Physician data 
collected  
The following data will be collected from the physicians who have agreed to 
participate: physician location, gender, medical specialty, type of activity (public 
hospital, private hospital, both hospital and office-based, other), number of GCA 
diagnosis within the last previous year, year of medical school graduation, 
number of years of practice. 
Patient data 
collected  
The following information will be recorded in an electronic Case Report Form 
(eCRF) using the data available in the medical file or collected during the visit (as 
part of the routine patient management): 
 Date of the inclusion visit (the only study visit) and type of visit (outpatient 
visit, day hospital, in-patient hospitalisation). 
 Patient eligibility criteria. 
 Demographic data: year of birth, gender, smoking status  
 Clinical data: height, weight, medical history, comorbidities related to GCs  
 GCA patient journey: Incident or prevalent patient (threshold: 6 weeks before 
visit), date of initial diagnosis, date of GCA signs/symptoms, physician(s) who 
referred the patient. 
 GCA characteristics: Initial presentation (cranial, polymyalgia rheumatica, 
extracranial, ESR/CRP, general signs), diagnosis methods, clinical form 
(relapsing, GCs-dependence, with GCA complications), GCA activity (clinical 
signs and symptoms) 
 Treatments: previous and on-going specific GCA treatments since diagnosis 
(GCs, immunosuppressants, targeted biologic therapy, Janus kinase 
inhibitors), treatments at diagnosis and inclusion visit, treatments for 
comorbidities related to GC intake. 
Four paper questionnaires (SF-36, EQ5D, FACIT-fatigue, global arteritis activity 
VAS) will be completed by the patient and one by the physician (global arteritis 
activity VAS). All questionnaires will be returned in the pre-paid reply envelope to 
the CRO in charge of the data entry. 
No safety data will be collected. Physicians will report adverse event as per usual 
French process, if appropriate. 
The use of indirectly personally identifiable data is crucial in this study since it will 
allow quality control. Physicians may be requested written corrections for missing 
or inconsistent data essential to the study. Patient identity will be coded in the 
eCRF and the questionnaires. The patients will be identified using a number 
made up of 4 digits: 3 digits for the investigator and 1 digit for the inclusion order 
number. The physician will maintain a patient identification table with patient’s 
identity and corresponding study number. This table will be stored by the 

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physician in a secure manner and no one else will have access to it. At the end 
of the study, the physician will be responsible for destroying this table. 
 
Statistical 
analyses 
 
Study populations 
3 populations will be defined for the analyses: 
 Population of Physicians: all the specialists who have included at least one 
patient fulfilling the inclusion criteria for the study 
 Total Population: all included patients  
 Analysis Population: included patients meeting the eligibility criteria 
 
General statistical methods 
The analyses of the primary and secondary objectives will be performed on the 
Analysis Population. 
The statistical analysis will be performed using SAS® software, version 9.3 or 
upper.  
The descriptive summary statistics will be for quantitative parameters: mean, 
standard deviation, median, first and third quartiles, minimum and maximum, filled 
and missing data. For qualitative parameters statistics will be frequency, 
percentage per modality, filled and missing data.  
As this is a descriptive study, no statistical testing will be performed. However, 2 
sided 95% confidence intervals will be calculated for every relevant proportion / 
mean. 
 
Primary objective analysis 
In order to describe medical practices in patients with GCA, the following end 
points will be used on the analysis population: 
Patient journey  
 Proportions of each physician who referred the patient 
 Proportions of each physician who follows the patient for his/her GCA 
(internist/rheumatologist) 
 Time between signs/symptoms and diagnosis: described as quantitative 
variable and as qualitative variable (early diagnosis / diagnosis in the standard 
time / late diagnosis).  

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The 3 endpoints will be described overall and by subgroups: the first 2 endpoints 
will be described by time between signs/symptoms and diagnosis (qualitative 
variable) and the 1st and 3rd endpoints will be described by type of physicians who 
follows the patient. 
Diagnostic mean 
 Proportions of each diagnostic method used  
The diagnostic mean will be described overall, by time between signs/symptoms 
and diagnosis (qualitative variable), and by type of physicians who follows the 
patient. 
Previous and on-going specific GCA treatments since diagnosis 
 Previous and on-going specific GCA treatments since diagnosis 
Treatments will be coded using the WHO Drug medicine dictionary (ATC codes). 
They will be described overall and by type of physician who follows the patient. 
 
Planned Study 
duration and 
schedule 
The planned recruitment period of patients will be 5 months, from the 1st of June 
to the 31th of October 2018. 
 
Study Milestones 
Milestone 
Planned Date 
Study start date (start of enrolment 
and data collection) 
01/06/2018 
Study end date (end of enrolment and 
data collection) 
31/10/2018 
Interim analysis 
NA 
Final report of study results 
Q2 2019 
 
 

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CONTENT 
 
1 
INTRODUCTION AND RATIONALE FOR THE STUDY .................................... 13 
2 
STUDY OBJECTIVES ................................................................................................. 15 
2.1 
Primary objective .......................................................................................................... 15 
2.2 
Secondary objectives ..................................................................................................... 15 
3 
STUDY METHODOLOGY ......................................................................................... 15 
3.1 
General methodology .................................................................................................... 15 
3.2 
Constitution and role of the Scientific Committee ..................................................... 16 
3.3 
Study duration and provisional schedule ................................................................... 17 
3.4 
Physician recruitment and study initiation ................................................................ 17 
3.4.1 
Definition of the source file for physicians ................................................ 17 
3.4.2 
Methods of recruitment of the specialist physicians .................................. 18 
3.4.3 
Recruitment hypotheses .............................................................................. 18 
3.4.4 
Initiation of the study .................................................................................. 18 
3.5 
Patient selection ............................................................................................................. 18 
3.5.1 
Patient selection method ............................................................................. 18 
3.5.2 
Information and consent ............................................................................ 19 
4 
STUDY POPULATIONS ............................................................................................. 19 
4.1 
Physician population ..................................................................................................... 19 
4.2 
Patient population ......................................................................................................... 19 
4.2.1 
Inclusion criteria ......................................................................................... 19 
4.2.2 
Non-inclusion criteria ................................................................................. 20 
4.2.3 
Withdrawal from the study ......................................................................... 20 
5 
CONDUCT OF THE STUDY AND DATA TO BE COLLECTED ........................ 20 
5.1 
Conduct of the study ..................................................................................................... 20 
5.1.1 
Inclusion consultation (single study visit) .................................................. 20 
5.2 
Physician Data collected ............................................................................................... 20 
5.3 
Patient Data collected ................................................................................................... 21 
5.3.1 
Case report form .......................................................................................... 21 
5.3.2 
Questionnaires ............................................................................................ 24 
5.3.2.1 
Self-assessment patient questionnaires: ...................................................... 24 
5.3.2.2 
Physician questionnaire: ............................................................................. 24 
6 
ENDPOINTS ................................................................................................................. 25 
6.1 
Primary endpoints ........................................................................................................ 25 
6.2 
Secondary endpoints ..................................................................................................... 25 
7 
STATISTICAL METHODS ........................................................................................ 26 
7.1 
Rationale for the number of patients and physicians ................................................ 26 
7.1.1 
Number of patients required ....................................................................... 26 
7.1.2 
Number of physicians ................................................................................. 26 
7.2 
Statistical analyses ........................................................................................................ 26 
7.2.1 
General statistical methods ......................................................................... 26 
7.2.2 
Study populations ........................................................................................ 26 
7.2.3 
Analysis of the physician and patient populations .................................... 27 
7.2.3.1 
Analyses of primary objectives: ................................................................... 27 
7.2.3.2 
Analyses of secondary objectives ................................................................. 28 
7.2.4 
Schedule for data analysis .......................................................................... 30 
8 
DATA MONITORING AND CONTROL .................................................................. 30 
8.1 
Centralised monitoring and controls .......................................................................... 30 

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8.2 
Audit and on-site inspections ....................................................................................... 31 
9 
LIMITATIONS OF THE STUDY .............................................................................. 31 
9.1 
Bias in selection of the physicians and the patients during recruitment ................. 31 
9.1.1 
Pre-inclusion controls ................................................................................. 31 
9.1.1.1 
Selection of physicians ................................................................................. 31 
9.1.1.2 
Patient selection ........................................................................................... 31 
9.1.2 
Post-inclusion controls ............................................................................... 31 
10 
REPORTING OF ADVERSE REACTIONS ............................................................. 32 
11 
STUDY DISCONTINUATION ................................................................................... 32 
12 
ETHICAL AND LEGAL CONSIDERATIONS ........................................................ 32 
12.1 Regulatory framework of the study ............................................................................ 32 
12.2 Responsibility and insurance by CHUGAI PHARMA FRANCE ............................ 33 
12.3 Submission of the study contracts and protocol ........................................................ 33 
12.3.1 
Ethics Committee ........................................................................................ 34 
12.3.2 
Protection of personal data ......................................................................... 34 
12.3.3 
Submission of financial agreements to Medical Council .......................... 34 
12.3.4 
Sunshine act ................................................................................................ 34 
12.4 Protocol amendment(s) ................................................................................................. 34 
12.5 Information for patients and confidentiality of the collected data ........................... 35 
12.6 Rationale for the use of personal data ........................................................................ 35 
12.7 Financial agreement with the physicians .................................................................... 35 
12.8 Delegation of duties by the physician .......................................................................... 36 
12.9 Archiving ....................................................................................................................... 36 
13 
DOCUMENTATION AND USE OF THE STUDY RESULTS ............................... 36 
13.1 Documentation of the study results ............................................................................. 36 
13.1.1 
Documents completed by the physician ...................................................... 36 
13.1.2 
Documents completed by the patient .......................................................... 37 
13.1.3 
Study report ................................................................................................. 37 
13.2 Use of the study results ................................................................................................. 37 
14 
BIBLIOGRAPHICAL REFERENCES ...................................................................... 38 
15 
APPENDICES ............................................................................................................... 40 
15.1 Appendix 1: 36-Item Short Form Survey Instrument (SF-36) ................................. 40 
15.2 Appendix 2: EuroQol-5 Dimensions - 3 Level version (EQ-5D-3L) ......................... 45 
15.3 Appendix 3: FACIT Fatigue Scale .............................................................................. 47 
15.4 Appendix 4: Global Arteritis Activity Scale (VAS) ................................................... 47 
 
 
 
 

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LIST OF FIGURES 
 
Figure 1 Study design ............................................................................................................. 16 
 
 
 
ABBREVIATIONS 
 
 
CPF 
CHUGAI PHARMA FRANCE 
CRO 
Contract Research Organization 
EGB 
Echantillon Généraliste des Bénéficiaires 
EQ5D 
EuroQol-5 Dimensions 
EULAR 
European League Against Rheumatism  
GCs 
GlucoCorticoids 
GCA 
Giant Cell Arteritis 
LTD 
Long-Term Disease 
MTX 
Methotrexate  
PET 
Positron Emission Tomography  
PMR 
PolyMyalgia Rheumatica 
SAP 
Statistical Analysis Plan 
SF-36 
36-Item Short Form Survey Instrument 
TAB 
Temporal Artery Biopsy 
VAS 
Visual Analog Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
INTRODUCTION AND RATIONALE FOR THE STUDY 
Giant cell arteritis (GCA) - also known as temporal arteritis, cranial arteritis, or Horton’s disease 
- is a form of immune-mediated inflammatory systemic vasculitis that affects large and medium-
sized arteries, predominantly affecting the extracranial branches of the carotid arteries and the 
subclavian and axillary branches of the aorta (Zöller et al. 2013). GCA may present with 
systemic symptoms such as fever, but the most common symptom is temporal and occipital 
headache accompanied by scalp tenderness (Babigumira et al. 2017). The arterial blockage 
associated with GCA leads to ischemic symptoms such as jaw claudication, intermittent 
claudication of the tongue and muscles involved in swallowing, and rarely infarction of the scalp 
or the tongue (Babigumira et al. 2017). 
GCA causes significant complications, particularly vision loss (4% for patients with large-vessel 
GCA and 11% for those with cranial disease (Muratore et al. 2014). GCA patients are also 
17.3 times (95% CI, 7.9 to 33.0) more likely to develop thoracic aortic aneurysm and 2.4 times 
(95% CI, 0.8 to 5.5) more likely to develop isolated abdominal aortic aneurysm (Evans, 
O’Fallon, et Hunder 1995). 
The mainstay of GCA clinical management is initiation of high-dose glucocorticoids (GCs), 
typically prednisone from 0.7 to 1mg/kg/day (PNDS 2017) maintained and tapered gradually. 
In most patients, the administration of high-dose GCs is followed by a rapid improvement of 
systemic inflammatory signs, presumably due to the effective suppression of interleukin-6 and 
the acute-phase response. In current practice, the tapering of GCs is generally started once 
reversible clinical signs have abated and laboratory values have been normalized. The dose 
of prednisone is initially reduced by 10 to 20% every 2 weeks; once the dose falls below 10 
mg per day, tapering is usually slowed (generally by 1 mg per month). These recommendations 
match those developed by the British Society for Rheumatology (BSR) (Dasgupta et al. 2010) 
and by the French study group for Large Vessel Vasculitis (GEFA) (Bienvenu et al. 2016a). 
Guidelines from the European League Against Rheumatism (EULAR) suggest a faster initial 
tapering to a dose of 10 to 15 mg per day within 3 months after treatment initiation (Mukhtyar 
et al. 2009). 
It is well-known that GC treatment may cause various adverse effects. During a 10-year follow-
up of a population-based cohort of patients with GCA, more than 80% had at least one 
complication related to GC treatment (Proven et al. 2003). The risk of cardiovascular 
comorbidities was over 6 times greater in GCA patients compared to matched controls (Pugnet 
et al. 2016). 
Different 
steroid-sparing 
agents 
have 
been 
used, 
from 
antimalarial 
agents 
to 
immunosuppressants (Kötter et al. 2012) and targeted biologics therapies (Bienvenu et al. 
2016b) with a more or less high level of evidence. 
Recommendations from the EULAR include the use of methotrexate (MTX) as a potential 
adjunct to GCs in patients with large-vessel vasculitis (Mukhtyar et al. 2009), but supporting 
evidence is limited. A meta-analysis of three placebo-controlled randomized trials involving 
patients with newly diagnosed GCA showed that a regimen of GC therapy plus MTX as 
compared with GCs alone confers a significant but modest benefit in lowering the relapse rate 
and in reducing the cumulative dose of GCs, without reducing the side effects of the GCs (Mahr 
et al. 2007). 

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Among biologics, the interleukin-6 receptor antagonist tocilizumab has shown efficacy in the 
induction and maintenance of remission in patients with GCA in a phase III randomized double-
blind, placebo-controlled trial combined with a 26-week prednisone taper (Stone, Klearman, et 
Collinson 2017). Tocilizumab has a marketing authorisation since September 18th, 2017 in 
Europe. 
There are currently few real-world data available in France on the management of patients 
with GCA, on their treatment sequences, as well as on the costs related to their health care 
consumption.  
To answer these questions, a first observational retrospective cohort study was conducted, 
using the EGB (Echantillon Généraliste des Bénéficiaires) database, which is a 1% random 
and representative sample of the French national Health insurance system.  
EGB contains anonymous demographic and comprehensive medical data on conditions with 
long-term disease (LTD) status, hospitalizations, and reimbursement claims for medications 
dispensed in the community setting. The study used the data collected between January 1st, 
2007 and December 31, 2015. Patients ≥50 years old, with a hospitalization for GCA and/or 
LTD status for GCA (M31.5 or M31.6 ICD-10 codes) and with at least 4 drug dispensing of oral 
GCs within 6 months around the index date were included. 
The index date was defined as the date of first occurrence of GCA code and cases were 
considered being incident if the GCA code first occurred after a minimal follow-up of 2 years. 
A treatment sequence was defined as the start of a new drug or the resumption of the same 
drug after a stop of drug dispensing ≥ 3 months. Annual incidence rates were calculated for 
the period 2009 to 2015 by using the people recorded in the EGB database as denominator. 
Briefly, the results were the following: among the 752,717 patients recorded in the EGB 
database, 241 people fulfilled inclusion criteria with a mean follow-up of 3.7 (±2.6) years. 
Annual incidence was ranging between 7 and 10/100,000 people ≥50 years-old that is 2300 
patients/year.  Demographic analyses showed that 72% of the patients were females and that 
mean age was 77.5 (±8.9) years. 74.3% of the patients had at least one proxy (i.e ICD-10 code 
or a treatment) for hypertension, 39.4% for depression/insomnia and 33.6% for osteoporosis. 
After index date, temporal artery biopsy (TAB) was performed in 43.2%, high-resolution color 
Doppler ultrasound in 35.3% and 18FDG-positron emission tomography (PET) in 11.6%.  
Regarding treatments, 84.3% of the patients used only GCs while 16.7% also received 1 to 3 
adjunctive medications, mainly MTX. Mean 1st GCs sequence duration was 17.2 months 
(±16.5) in 96.6% of the patients. 
EGB database strengths included comprehensive patient demography, epidemiology, 
diagnostic methods and treatment sequences. In contrast, limited data were available for 
comorbidities (as only proxies were described), clinical presentations (cranial, polymyalgia 
rheumatica [PMR], extracranial), clinical forms (relapsing, GCs-dependant), doses of GCs 
used, cumulative GCs doses and GCs associated toxicities. In addition, patient journey was 
poorly described given that patients may be first seen by a variety of physicians according to 
their first signs and symptoms (e.g. ophthalmologist for blurred vision, neurologist for 
headache, etc.), data which was not available in the EGB database analysis. 

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The proportions of use of TAB, Ultrasound or PET have also to be confirmed as they thought 
to be unusually performed in the EGB analysis. 
We propose to conduct an observational study aiming to describe GCA management and 
patient characteristics in France. 
 
2 
STUDY OBJECTIVES 
2.1 
Primary objective 
The primary objective is to describe medical practices in patients with GCA in terms of patient 
journey, diagnostic methods and specific GCA treatments since diagnosis. 
2.2 
Secondary objectives 
The secondary objectives of this study are: 
 To describe comorbidities related to GCs and associated treatments 
 To describe GCA characteristics in terms of GCA duration, initial presentation, clinical form 
and GCA activity 
 To describe the health status of GCA patients 
 To describe physician and patient characteristics 
 
3 
STUDY METHODOLOGY 
3.1 
General methodology 
This is a cross-sectional, non-interventional, national (France), multicentre study, conducted 
on a population of 300 patients with GCA, to describe GCA management and patient 
characteristics (Figure 1). 
The study will be conducted in accordance with the professional code of ethics and the good 
epidemiological practice guidelines developed by the Association of French-Speaking 
Epidemiologists)(ADELF; 2017) and the STROBE (STrengthening the Reporting of 
OBservational studies in Epidemiology) recommendations for the drafting of reports and 
publications related to the study (Vandenbroucke et al. 2007) (see also Section 12 for the full 
regulatory framework). 
The information will be collected during a single visit to the internist or rheumatologist as part 
of the usual management of the patient with GCA. This study does not require any additional 
specific examination. Data will be collected from the medical file and from patient 
questionnaires on health status (SF-36 [36-Item Short Form Survey Instrument] McHorney, 
Ware, et Raczek 1993; Ware et Sherbourne 1992, EQ5D [EuroQol-5 Dimensions] Brooks 
1996; EuroQol Group 1990; Rabin et al. 2014 and fatigue [FACIT-fatigue] Webster, Cella, et 
Yost 2003). In addition, GCA activity will be evaluated using a global arteritis activity Visual 

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Analog Scale (VAS) to be completed by the patient and the physician. These questionnaires 
are detailed in Section 5.3.2. 
 
Figure 1 Study design 
 
GCA: Giant Cell Arteritis; eCRF: electronic Case Report Form; VAS: Visual Analog Scale 
 
3.2 
Constitution and role of the Scientific Committee 
A specialised Scientific Committee has been established to advise and support CHUGAI 
PHARMA FRANCE (CPF), to refine and validate the entire scientific project, including its 
scientific relevance and its objectives, modalities for selecting physicians and patients, the 
documents used for data collection, data quality control procedures during the study and the 
clinical interpretation of the statistical results. 
In addition, the Scientific Committee will be consulted by CPF on any medical or scientific 
questions arising during the study as well as for validation of the statistical analysis plan, for 
the presentation of the final results to refine the analyses and to support a scientific 
communication plan of the results.  
The four members of the Scientific Committee are: 

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 Prof Valerie Devauchelle-Pensec, Rheumatology Department, CHU LA CAVALE 
BLANCHE, BREST  
 Prof Eric Hachulla, Internal Medicine Department, CHRU LILLE, LILLE 
 Prof Alfred Mahr, Internal Medicine Department, HOPITAL SAINT LOUIS, PARIS 
 Prof Marc Paccalin, Internal Medicine and Geriatic Medicine Department, CHU LA 
MILETRIE, POITIERS  
 
3.3 
Study duration and provisional schedule 
The planned dates for the study milestones are provided in Table 1. 
The planned period for recruiting patients will be 5 months, from the 1st of June to the 31th of 
October 2018. 
 
Table 1 Study Milestones 
Milestone 
Planned Date 
Study start date (start of enrolment and data 
collection) 
01/06/2018 
Study end date (end of enrolment and data 
collection) 
31/10/2018  
Interim analysis 
NA 
Final report of study results 
Q2 2019 
The overall duration of the study or the duration of the patient recruitment period may vary 
depending on the rate at which patients are included or the time it takes to obtain regulatory 
authorisations. 
 
3.4 
Physician recruitment and study initiation 
3.4.1 
Definition of the source file for physicians 
The physician population in this study will include internists and rheumatologists who manage 
patients suffering from GCA in hospitals or private clinics in France and agree to take part in 
the study. 
A national data base provided by an independent company (CEGEDIM) including 
approximately 2600 internists and rheumatologists practicing in hospitals or private clinics in 
Metropolitan France will be used to recruit 150 active physicians for the study. 

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Physician will be selected by the Sponsor following rules and recommendations on relations 
between industry and health professionals. 
 
3.4.2 
Methods of recruitment of the specialist physicians  
A mailing including a reply coupon will be sent to all physicians mentioned in Section 3.4.1. 
This mailing will contain information about the study. A telephone follow-up phase is planned 
for physicians who have not responded to the mailing until the physician recruitment objective 
is met.  
A Participation Agreement will be sent to each physician interested in participating in the study.  
Once a site is initiated, the professional characteristics of the physician will be collected. The 
data will be used to perform a comparison with national data, in order to identify a potential 
selection bias (see also Section 9.1) 
 
3.4.3 
Recruitment hypotheses  
The recruitment objective is 150 active physicians (i.e. will include at least one patient). 
 
3.4.4 
Initiation of the study 
Following the signature of the study financial contract, physicians will be provided with all the 
study material (sent by post).  
The participating physicians will then be trained on the study protocol and its practical aspects 
by telephone or online (video posted on a website) according to their preference.  
If the physician chooses a study initiation by video, he/she will receive a login and password 
to access to a website where the initiation video will be uploaded. 
During this telephone contact or video, all the key points necessary to the proper conduct of 
the study will be addressed: the rationale and objectives of the study, regulatory requirements 
(patient information form, etc.), and also the technical requirements (data collection, shipment 
of the questionnaires, etc.). If the study is initiated by a telephone call, the minutes of the 
discussion and a presentation will be sent to the physician. In case of a study initiation by 
video, a quiz will be submitted to the physician to ensure that the training has been understood. 
 
3.5 
Patient selection 
3.5.1 
Patient selection method 
Physicians will start patient inclusion only when the study is initiated at their site and when all 
regulatory authorisations are obtained. 
It is expected that 300 patients (prevalent or incident cases) will be recruited in this study. 
Based on the previous EGB database analysis, there are 2300 incident patients/year in France. 
Thus, including 300 incident and prevalent patients during the recruitment period, even 
excluding summer holidays, seems realistic (see also Section 7.1). 

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Each physician will be requested to include consecutively during the inclusion period all the 
patients meeting the eligibility criteria listed below and accepting to participate in the study.  
 
3.5.2 
Information and consent  
The physician must inform the patient about the study before inclusion and seek her/his non-
opposition. A patient information form will be given to each patient by the physician. It will 
explain the purpose of collecting and processing the data, the nature of data collected, the 
persons who will receive the data, the patient’s right to access and correct the data and also 
the patient’s right to object to transmission of the data (as specified by the CNIL). The original 
will be kept by the investigator and a copy will be given to the patient. 
Patients who are eligible to take part in the study and who verbally agree to their data 
undergoing automated processing (as defined by CNIL), will be included in the study by the 
physicians, who will enter the corresponding data in the eCRF. The patient agreement will be 
only verbal and will NOT include the collection of a non-opposition form.  
Patient decision to participate or not in the study will be written in his/her medical file by the 
physician. 
 
4 
STUDY POPULATIONS 
4.1 
Physician population 
In total, 150 internists and rheumatologists practicing in hospitals or private clinics in 
Metropolitan France are expected to participate actively in the study (i.e. inclusion of at least 1 
patient) (see also Section 3.4 for the physician recruitment method).  
In order to avoid any over-representation of a particular site or hospital, a maximum of 10 
patients per hospital department will be able to participate in the study. Each physician will 
have a specific site number. 
 
4.2 
Patient population 
A total of 300 patients meeting the selection criteria listed below will be included in the study. 
 
4.2.1 
Inclusion criteria 
Patients must meet the following criteria to be included in the study:  
 At least 50 years old.  
 Suffering from GCA as per investigator judgement, newly diagnosed or not.  
 Starting or under treatment for GCA.  

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 Informed verbally and in writing about this study and not objecting to their data being 
electronically processed or subjected to data quality control. 
 
 
4.2.2 
Non-inclusion criteria 
Patients fulfilling the following criteria cannot be included in the study:  
 Unable to consent  
 Participation to a randomised controlled clinical trial 
 
 
4.2.3 
Withdrawal from the study 
In this cross-sectional study, no specific criteria are defined for withdrawal from the study. The 
patient can refuse at any time that his/her data are analysed.  
 
5 
CONDUCT OF THE STUDY AND DATA TO BE COLLECTED  
5.1 
Conduct of the study 
5.1.1 
Inclusion consultation (single study visit) 
Once the study initiation has been completed, patients will be included consecutively after 
verification that they meet the selection criteria (see section 4.2).  
The information will be collected during a single visit to the internists and rheumatologist as 
part of the usual patient management of his/her GCA. The physician will explain the purpose 
of the study to the patient with an information form specific to the study and will inform him/her 
of the option to refuse or withdraw from participation. A copy of the information form will be 
given to the patient and the original will be kept by the physician.  
The physician will perform this visit as part of the usual patient management and will not 
perform any additional examinations specific to the study. 
The data collected from the medical file will be recorded on an electronic case report form 
(eCRF). Self-assessment questionnaires about health status (SF-36, EQ-5D), GCA activity 
(global arteritis activity VAS) and fatigue (FACIT-fatigue) (see also Section 5.3.2) will be 
proposed to the patient. He/she will have to complete them during the course of the visit. The 
physician will also complete a copy of the global arteritis activity VAS on paper. All 
questionnaires will be returned in the pre-paid reply envelope to the CRO ITEC Services, in 
charge of the data entry.  
 
5.2 
Physician Data collected  
The following data will be collected from the physicians who have agreed to participate: 
 Physician location 

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 Gender 
 Medical specialty  
 Type of activity: public hospital, private hospital, both hospital and office-based, other 
 Number of GCA diagnosis within the last previous year 
 Year of medical school graduation 
 Number of years of practice 
The analyses of this data will allow to identify any physician recruitment bias (see also Section 
9.1.2). 
The information will be recorded by the physician in the eCRF.  
 
5.3 
Patient Data collected 
Patient identity will be coded in the eCRF and the self-assessment questionnaires. Patients 
will be identified using a number made up of 4 digits: 3 digits for the investigator and 1 digits 
for the inclusion order number (see also Section 12.5 on data confidentiality).  
 
5.3.1 
Case report form 
No information related to patient identity (initials, full date of birth, etc) will be entered in the 
eCRF. 
The following information will be recorded in the eCRF using the data available in the medical 
file or collected during the visit (as part of the routine patient management): 
 Date of the inclusion visit (the only study visit) and type of visit (outpatient visit, day hospital, 
in-patient hospitalisation). 
 Patient eligibility criteria. 
 Demographic data:  
o Year of birth, gender,  
o Smoking status (smoker, never smoker),  
 Clinical data:  
o Height, weight (at diagnosis, at the inclusion visit)  
o Medical history:  
 
significant past and current comorbidities (e.g. diabetes, high blood 
pressure, 
dyslipidaemia, 
osteoporosis, 
neuropsychiatric 
disorders, 

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depression, insomnia, serious infection disease, parasitic diseases, cancer, 
stroke, coronary artery disease, ischemic cardiopathy, peripheral artery 
diseases, adrenal insufficiency, cataract, glaucoma, gastro-intestinal ulcer, 
digestive perforation, other significant history),  
 
start and stop date (month, year) of comorbidities 
o Comorbidities related to GCs for GCA patients (i.e. which appeared or worsened 
during GCs treatment according to the investigator judgement).  
 GCA patient journey:  
o Incident or prevalent patient: 
 
Newly diagnosed (i.e. incident) patient will be defined as patient with GCA 
diagnosis within the last 6 weeks before visit 
 
Not newly diagnosed (i.e. prevalent) patients will be defined as patient with 
GCA diagnosis more than 6 weeks before visit 
o Date of initial diagnosis 
o Date of GCA signs/symptoms (month and year) 
o Physician(s) who referred the patient (General Practitioner, Ophthalmologists, 
Neurologist, Emergency, Internist, Rheumatologist, Other). 
 GCA characteristics:  
o Initial presentation at diagnosis and inclusion visit: 
 
Cranial (localized headache, scalp tenderness, temporal artery tenderness 
or decreased pulsation, ischemia-related vision impairment / loss, mouth or 
jaw pain upon mastication, stroke or transient ischaemic attack (TIA), other) 
 
PMR (morning stiffness and/or pain in the shoulder and/or pelvic girdles, 
inflammatory arthromyalgia, peripheral arthritis, other)  
 
Extracranial (large-vessel GCA i.e. thoracic or abdominal aortic aneurysm, 
myocardial infraction, dilatation, limb claudication, subclavian stenosis, 
other) 
 
ESR/CRP  
 
General signs: fever, weight loss (%), health status modification 
Start date for all signs and symptoms (month, year) 
o Diagnostic methods: TAB, High-resolution color Doppler ultrasound of the temporal 
arteries, MRI of the temporal arteries, 18FDG-PET, Computed tomography 

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angiography 
(CTA), 
Magnetic 
resonance 
angiography, 
signs/symptoms, 
erythrocyte Sedimentation Rate (ESR), C-Reactive protein (CRP), other. 
o Clinical form: 
 
Relapses: date (month, year), treatments and doses, criteria for identifying 
relapse (clinical, biological, other) 
 
GCs-dependence: dose of prednisone after GCA diagnosis 
 
Complications during the course of the disease: ischemia-related vision 
loss, stroke, TIA, thoracic or abdominal aortic aneurysm, other. 
 GCA activity:  
o Clinical signs and symptoms of GCA activity at diagnosis and at inclusion: GCA-
related fever (> 38°C), symptoms of PMR (morning stiffness and/or pain in the 
shoulder and/or pelvic girdles, inflammatory arthromyalgia, peripheral arthritis, 
other), localised headache, temporal artery or scalp tenderness, visual signs or 
symptoms (e.g. acute or subacute vision loss due to arteritic anterior ischemic optic 
neuropathy; A-AION), transient blurry vision (generally monocular or at least 
affecting one eye at a time, but potentially affecting both eyes), jaw or mouth pain, 
extremity claudication, other features judged by the investigator to be consistent 
with a GCA or PMR flare. 
Start date of signs and symptoms (month, year) 
 
 Treatments:  
o Previous and on-going specific GCA treatments since diagnosis:  
 
GCs (start and end date, dose/day, administration route, current dose, 
cumulative dose, kinetic) 
 
Immunosuppressants 
(MTX, 
cyclophosphamide, 
cyclosporine, 
azathioprine, 
mycophenolate 
mofetil, 
leflunomide, 
dapsone, 
hydroxychloroquine, other) (start and end date, dose at starting date, 
current dose, maximum dose) 
 
Targeted biologic therapy (adalimumab, etanercept, abatacept, tocilizumab, 
infliximab, other) (start and end date, dose at starting date, current dose) 
 
Janus Kinase inhibitors (start and end date, dose at starting date, current 
dose) 
o Treatments at diagnosis and inclusion visit: antiplatelet agents, statins, 
antiosteoporotic treatments, antihypertensive (start date, treatment name). 
o Other significant concomitant treatments (start and end date, indication) 

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o Treatments for comorbidities related to GC intake (start and end date, indication) 
No safety data will be collected. Physicians will report adverse event as per usual French 
process, if appropriate. 
 
5.3.2 
 Questionnaires 
Four paper questionnaires will be completed by the patient and one will be completed by the 
physician. All questionnaires will be returned in the pre-paid reply envelope to the CRO ITEC 
Services, in charge of the data entry. 
 
5.3.2.1 
Self-assessment patient questionnaires:  
 SF-36 (McHorney, Ware, et Raczek 1993; Ware et Sherbourne 1992): The SF-36 
questionnaire is a generic health status instrument evaluating 8 dimensions through 36 
questions: physical functioning, bodily pain, role limitations due to physical health 
problems, role limitations due to personal or emotional problems, emotional well-being, 
social functioning, energy/fatigue, and general health perceptions. An additional item 
provides an indication of perceived change in health (Annexe 15.1). 
 EQ5D-3L (Brooks 1996; EuroQol Group 1990; Rabin et al. 2014): The EQ-5D 
questionnaire is a generic health status instrument composed of 5 questions and a VAS. 
The questions explore 5 dimensions: mobility, self-care, usual activities, pain/discomfort 
and anxiety/depression. Each dimension has 3 levels: no problems, some problems, 
extreme problems. The visual analogue scale evaluates the perceived health state 
(Annexe 15.2).  
 FACIT-fatigue (Webster, Cella, et Yost 2003): FACIT-Fatigue is an instrument that 
measures overall fatigue and its effects on the general functioning and daily activities 
through 13 questions. Completion of the questionnaire should be based on a 7-day recall 
period. Each question has 5 levels: not at all, a little bit, somewhat, quite a bit, very much. 
Lower scores indicate greater fatigue (Annexe 15.3). 
 Patient global arteritis activity VAS: This VAS measures global arteritis activity on a scale 
of 100 mm labelled with “no disease activity” (symptom-free and no arteritis symptoms) at 
the extreme left and with “maximum disease activity” (maximum arteritis disease activity) 
at the extreme right. The patient will be asked to indicate his/her disease activity by drawing 
a line on the scale (Annexe 15.4). 
 
5.3.2.2 
Physician questionnaire:  
 Physician global arteritis activity VAS: This VAS measures global arteritis activity, as 
described above. The physician will be asked to indicate the patient disease activity by 
drawing a line on the scale. 
 

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6 
ENDPOINTS 
6.1 
Primary endpoints 
The endpoints of the primary objective To describe medical practices in patients with GCA in 
terms of patient journey, diagnostic methods and specific GCA treatments since diagnosis are:   
 Patient journey (Proportions of each physicians who referred the patient, Proportions of 
each physicians who followed the patient for his/her GCA, Time between GCA 
signs/symptoms and diagnosis) 
 Proportions of each diagnostic method used 
 Previous and on-going specific GCA treatments since diagnosis 
 
6.2 
Secondary endpoints 
The endpoints of the objective To describe comorbidities related to GCs and associated 
treatments are:  
 Comorbidities related to GCs 
 Treatments in patients with comorbidities related to GCs 
 
The endpoints of the objective To describe GCA characteristics in terms of GCA duration, 
initial presentation, clinical form and GCA activity:  
 Proportion of incident patients: patients with a diagnosis of GCA ≤ 6 weeks from inclusion  
 Proportion of prevalent patients: patients with a diagnosis of GCA > 6 weeks from inclusion. 
 GCA duration  
 Initial presentation: Proportions of patients with cranial GCA, PMR, extracranial GCA, 
elevated ESR/CRP and general signs. 
 Clinical form: Proportion of patient with relapse and number of relapse, Distribution of GCs-
dependence, Proportions of patients with GCA complications 
 Proportions of each clinical signs/symptoms of GCA activity 
 Score of the physician and patient global arteritis activity VAS  
 
The endpoints of the objective To describe the health status of GCA patients are: 
 PRO scores: Total and detailed scores of the SF-36 questionnaire, detailed scores of the 
EQ5D-3L questionnaire, Total and detailed scores of the FACIT-Fatigue questionnaire 

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The endpoints of the objective To describe physician and patient characteristics are: 
 Demography, medical specialty, number of years of practice, type of practice and number 
of GCA diagnosis within the previous year for physicians,  
 Demography for patients 
 Significant past and current comorbidities of GCA patients and associated concomitant 
treatments 
 
7 
STATISTICAL METHODS  
7.1 
Rationale for the number of patients and physicians 
7.1.1 
Number of patients required 
Not applicable in a descriptive observational study 
7.1.2 
Number of physicians 
Not applicable 
 
7.2 
Statistical analyses 
The analysis will be performed by ITEC Services in accordance with this section and with the 
Statistical Analysis Plan (SAP) that supplements it. 
 
7.2.1 
General statistical methods 
The statistical analysis will be performed using SAS® software, version 9.3 or upper.  
A SAP describing the planned statistical analysis in detail with Tables, Figures and Listings 
(TFLs) templates will be developed as a separate document. This SAP will be finalised and 
validated before each database freeze by CPF. 
The descriptive summary statistics will be:  
 for quantitative parameters: mean, standard deviation, median, first and third quartiles, 
minimum and maximum, filled and missing data;  
 for qualitative parameters: frequency, percentage per modality, filled and missing data 
As this is a descriptive study, no statistical testing will be performed. However, 2 sided 95% 
confidence intervals will be calculated for every relevant proportion / mean.  
 
7.2.2 
Study populations 
Three populations will be defined for the analyses: 

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 Population of Physicians: all the specialists who have included at least one patient meeting 
the eligibility criteria for the study 
 Total Population: all included patients  
 Analysis Population: all included patients meeting the inclusion and non-inclusion criteria  
The number of potential exclusions from the patient population used for analysis and the 
reasons for these exclusions will be described. The patient disposition will be described. 
 
7.2.3 
Analysis of the physician and patient populations 
The analyses of the primary and secondary objectives will be performed on the Analysis 
Population. 
7.2.3.1 
Analyses of primary objectives:  
To describe medical practices in patients with GCA, the following endpoints will be described 
on the analysis population: 
Patient journey  
 Proportions of each physician who referred the patient 
 Proportions 
of 
each 
physician 
who 
follows 
the 
patient 
for 
his/her 
GCA 
(internist/rheumatologist) 
 Time between signs/symptoms and diagnosis: described as quantitative variable and as 
qualitative variable. (early diagnosis / diagnosis in the standard time / late diagnosis) 
The 3 endpoints will be described overall and by subgroups: the first 2 endpoints will be 
described by time between signs/symptoms and diagnosis (qualitative variable) and the 1st and 
3rd endpoints will be described by type of physicians who follows the patient.  
 
Diagnostic mean 
 Proportions of each diagnostic method used  
The diagnostic mean will be described overall, by time between signs/symptoms and diagnosis 
(qualitative variable), and by type of physicians who follows the patient. 
 
Previous and on-going specific GCA treatments since diagnosis 
 Previous and on-going specific GCA treatments since diagnosis  
Treatments will be coded using the WHO Drug medicine dictionary (ATC codes). They will be 
described overall and by type of physician who follows the patient. 
 

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7.2.3.2 
Analyses of secondary objectives 
The analysis of the secondary objectives will be performed on the analysis population.  
Description of comorbidities related to GCs and associated treatments 
 Current and past comorbidities of GCA patients (comorbidities related to GCs) will be 
coded using the medical dictionary MedDRA®. They will be described overall and by type 
of physicians who follows the patient. 
 Treatments in patients with comorbidities related to GCs will be coded using the WHO Drug 
medicine dictionary (ATC codes). They will be described overall and by type of physician 
who follows the patient. 
 
Description of GCA characteristics 
 Time between diagnosis and inclusion will be described as quantitative variable and as 
qualitative variable (patient newly diagnosed or not: incident or prevalent case) 
 Proportion of incident patients: patients with a diagnosis of GCA ≤ 6 weeks from inclusion  
 Proportion of prevalent patients: patients with a diagnosis of GCA > 6 weeks from inclusion. 
 
The following endpoints will be described overall and by type of patient (prevalent/incident), by 
time between signs/symptoms and diagnosis (qualitative variable), and by type of physicians 
who follows the patient: 
 GCA duration  
 Initial presentation: proportions of patients with cranial GCA, PMR, extracranial GCA, 
ESR/CRP, general signs 
 Clinical form  
o Proportion of patients with relapse and number of relapse, 
o Proportion of patients with recurrence and number of recurrences, 
o Dose of GCs-dependence  
o Proportion of patients with GCA complications. 
Analysis of potential factors associated to relapse will be performed using logistic regression. 
The associated factors will be defined in the SAP. 
 GCA activity 
o Proportions of each clinical signs/symptoms of GCA activity 

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o Scores of the patient and physician global arteritis activity VAS (quantitative 
variable) 
The concordance between the scores of the patient and physician global arteritis activity VAS 
will be evaluated using the kappa coefficient. 
The potential factors associated with the increase of the global arteritis activity will be studied. 
 
Description of the health status of GCA patients 
 SF-36 questionnaire 
The SF-36 is a self-report, 36 item survey measuring health-related quality-of-life. The SF-36 
consists of eight scaled scores. A score ranging from 0 (indicating the worse health status) to 
100 (indicating the best health status) is assigned for each domain. Scores and missing data 
of the SF-36 were handled according to the user’s manual. The score for each item of SF-36 
will be presented (in quantitative) as well as the total score for each domain. 
 
 EQ5D-3L questionnaire 
The EQ5D-3L consists of five questions relating to five dimensions of health. Respondents 
indicate which of a possible three statements best describe their current health state for each 
dimension. Each dimension has 3 levels: no problems, some problems, extreme problems. 
Respondents are asked to repeat this process for the five dimensions by indicating one level 
for each dimension, giving rise to scores ranging from 1 to 3, with scores of 3 on each 
dimension indicating the most severe impairment. Binary variables will be computed for each 
dimension dichotomising the levels into ‘No problems’ (level 1) and ‘Problems’ (levels 2 and 
3). Perceived current health state will be measured by asking respondents to indicate their 
current health state on a VAS with endpoints labelled 0 ‘Worst imaginable health state’ and 
100 ‘Best imaginable health state. The score for each item of EQ5D-3L will be presented (in 
qualitative variable at 2 and 3 modalities for 5 dimensions and in quantitative for VAS). 
 
 FACIT-Fatigue 
FACIT-Fatigue is a patient-reported rating scale consisting of 13 items that yields a summed 
total score ranging between 0 and 52 (52= less fatigue).  
The score for each items of FACIT-Fatigue will be presented (in qualitative variable) as well as 
the total score (quantitative variable). 
 
Description of physician and patient characteristics 
 Description of physicians 
The analysed data will be recorded by the physician in the eCRF. 

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The population of physicians in the study will be described overall, in terms of demographic 
parameters (geographic location, number of years of practice, year of medical school 
graduation), medical specialty, status of the health institution (public hospital, private hospital, 
both hospital and office-based, other) and number of GCA diagnosis within the previous year. 
 
 Description of patients 
Demographic data (age, gender, smoking status) and body mass index will be described 
overall and by type of physician who follows the patient. 
Current and past comorbidities of GCA patients (significant past and concomitant diseases) 
will be coded by the medical dictionary MedDRA®. They will be described overall and by type 
of physician who follows the patient. 
Treatments will be coded using the WHO Drug medicine dictionary (ATC codes). They will be 
described overall and by type of physician who follows the patient. 
 
7.2.4 
Schedule for data analysis 
The final analyses will be performed after the database lock and are planned for January 2019. 
 
8 
DATA MONITORING AND CONTROL 
8.1 
Centralised monitoring and controls 
Monitoring of the study will be performed by ITEC Services, which will ensure, through regular 
communication (follow-up telephone calls and/or sending out newsletters) that the study is 
being conducted in accordance with the protocol and the regulatory requirements. 
Monitoring visits will be conducted in 10% of active sites. The objective of these visits will be 
to validate the existence of the patients included in the study, and to check that the data 
reported in the CRF are consistent with the available source data. Monitoring visits will be 
described in the study monitoring guide and a monitoring report will be prepared after each 
visit. 
The first questionnaires from each site will be monitored upon reception to ensure that the 
completion method is correct and that a follow up training is not necessary. 
A specific Freephone number will be available for physicians having any questions related to 
the study. 
Requests for corrections will be sent by Data Management for missing or erroneous CRF data 
on a regular basis, according to the Data Management Plan of the study. They will be 
transmitted to the Epidemiology Research Associate, who will manage the resolution with the 
physician through the eCRF, followed by emails and phone calls if necessary.  
The monitoring procedures will be validated by CPF.  

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In addition, a Data Review Meeting will take place prior to the final statistical analysis. 
Decisions made during this meeting will be validated by the study Scientific Committee. 
 
8.2 
Audit and on-site inspections 
Prior to the start of the study, the investigator is required to confirm his/her agreement to 
conduct the study in accordance with the protocol and to give access to all relevant data and 
records to CPF monitors, auditors, and designated agents of CPF, IRBs/IECs, and regulatory 
authorities as required.  
If an inspection of the site is requested by a regulatory authority, the investigator must inform 
CPF immediately that this request has been made. 
 
9 
LIMITATIONS OF THE STUDY 
In order to extrapolate study results to the entire population, potential bias must be detected a 
priori and controlled as much as possible. 
In this cross-sectional study, the description of patient management can be subject to selection 
bias during the recruitment of the study population (if the source population is not 
representative of the target population; if the active physician and included patient samples 
are not representative of the source population) (see also Section 7.1). 
 
9.1 
Bias in selection of the physicians and the patients during recruitment 
9.1.1 
Pre-inclusion controls 
9.1.1.1 
Selection of physicians 
 
The physician selection method described in Section 3.4 should ensure the sample is 
representative.  
 
9.1.1.2 
Patient selection 
The patients included should be selected in a consecutive manner by the participating 
physicians once the study has been initiated and the selection criteria have been verified. In 
order to encourage inclusions in a consecutive manner, this obligation will be highlighted: 
 in the financial contract signed by the physician, 
 during regular follow-up contacts with the physicians during the recruitment period 
(telephone calls and/or Newsletters). 
 
9.1.2 
Post-inclusion controls 
At the end of the inclusion period, the characteristics of the physicians who are active in the 
study will be compared to those of the physicians in the source list, on the basis of the available 

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data. Any significant differences in these parameters will be discussed with the members of 
the study Scientific Committee. 
The distribution of included patients will be compared to the distribution of the specialists who 
are active in the study (geographic distribution and distribution by clinical practice facility). 
In addition, the patient and GCA characteristics at baseline will be discussed with the study 
Scientific Committee and compared to the data available in the literature at this time. 
 
10 
REPORTING OF ADVERSE REACTIONS 
This is a non-interventional epidemiological study. It does not aim to identify or quantify any 
safety risk related to an authorised medicine. Therefore, no safety data will be collected and 
no reporting of adverse reactions is expected in this study. 
Physicians will report adverse event as per usual French process, if appropriate. 
 
11 
STUDY DISCONTINUATION 
Planned study duration is 4 months (recruitment period and data collection). Given the cross-
sectional nature of the study, no study discontinuation is expected. If the patient withdraws 
her/his consent after the unique visit, all data generated until study discontinuation and the 
reasons for not completing the study will be collected.  
 
12 
ETHICAL AND LEGAL CONSIDERATIONS 
12.1 
Regulatory framework of the study 
This non-interventional study is conducted in accordance with Article L. 1121-1 of the French 
Code of Public Health defining non-interventional studies as "all the acts are practised and 
products used in the usual way, with no risk and constraint for the patient". 
This study does not result in any changes to the patient’s usual medical care, does not cause 
physical or psychological harm and does not require particular follow-up visits for subjects 
entering the study. The use of study drug is consistent with the marketing authorisation as 
referred to Article L.5121-8 of the French Code of Public Health (CSP). 
In this context, the study is not subject to the regulations applicable to interventional research. 
Competent Authority (French National Agency for Medicines and Health Products Safety - 
ANSM) authorisation is not required but a positive opinion from the French Ethics Committee 
will be mandatory before the start of the study. 
The study will comply with the MR003 methodology reference, in which case there is no 
specific regulatory procedures (check of the MR 003 applicability should be documented). 

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The study has been designed and shall be implemented in accordance with applicable 
regulation, including: 
 The French Code of Public Health (pharmacovigilance, the anti-gift law, transparency, 
Jardé law, etc), 
 regulations on the protection of personal data, 
 the Declaration of Helsinki, 
 "The ENCePP Code of Conduct for Scientific Independence and Transparency in the 
Conduct of Pharmacoepidemiological and Pharmacovigilance Studies, ENCePP, Rev.3 
editorial amendment 14 July 2016, 
 "Guide on Methodological Standards in Pharmacoepidemiology", European Network of 
Centers for Pharmacoepidemiology and Pharmacovigilance (ENCePP), EMA/95098/2010, 
Rev. 6 July 2017, 
 "Guideline on good Pharmacovigilance practices: Module VI – Collection, management 
and submission of reports of suspected adverse reactions to medicinal products (Rev 2) ", 
EMA, HMA, Rev.2 28 July 2017, 
 "Good Epidemiological Practice (GEP)", International Epidemiological Association (IEA), 
November 2007 
 "Guidelines for Good Pharmacoepidemiology Practices (GPP)", International Society for 
Pharmacoepidemiology (ISPE), June 2015 
 "STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) 
guidelines" (Vandenbroucke, et al 2008) 
 the Recommendations of Ethics and Good Practices in Epidemiology (French version - 
2007), ADELF, ADEREST, AEEMA, EPITER. 
 
12.2 
Responsibility and insurance by CHUGAI PHARMA FRANCE 
In France, since this study does not fall within the framework of biomedical research, no 
insurance is required. 
 
12.3 
Submission of the study contracts and protocol 
Before the start of the study, the study protocol, the patient information form and all the other 
relevant documents will be submitted to the competent authorities in accordance with 
applicable legislation. All ethical and legal obligations must be met before the first patient is 
included in the study. 
 

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12.3.1 
Ethics Committee 
Pursuant to Law No. 2012-300 of March 5, 2012 on research involving humans (known as "Loi 
Jardé"), the study will be submitted to an Ethics Committee. 
 
12.3.2 
Protection of personal data 
In accordance with Article 54 of Act No 78-17 of January 6, 1978 as amended, the processing 
of personal data for this non-interventional study is in accordance with Decision No 2016-263 
of July 21, 2016 on the approval of a reference methodology for the processing of personal 
data used in medical research (MR-003), published in the OJ on August 14, 2016. CPF has 
signed a commitment to be compliant with reference methodology MR003 (02.03.2018 / n°: 
2158700 v 0). 
 
12.3.3 
Submission of financial agreements to Medical Council  
According to the Act on various social measures (DMOS - amended by the law of March 4, 
2002), Article L. 4113-6 of the French Code of Public Health (CSP) prohibits companies 
"benefiting, producing or marketing products covered by compulsory social security schemes" 
from offering or providing direct or indirect benefits to healthcare professionals or associations 
representing or defend the interests of them. Article L. 4113-6 of the French Code of Public 
Health allows exemption if: 
 an agreement with the healthcare professionals exists, 
 the purpose of this agreement relates to research activities, 
 this agreement is submitted for approval to the competent National Medical Council, which 
evaluate adequacy of the fees. 
Therefore, the site agreements will be submitted to the French National Council of Physicians 
to seek a positive opinion. 
 
12.3.4 
Sunshine act 
In accordance with Article L. 1453-1 of the French Code of Public Health (Article 2 of Law No 
2011-2012 of 29 December 2011 on the Strengthening of Health Protection for Medicinal and 
Health Products) and Decree no. ° 2013-414 of May 21, 2013, CPF will disclose any 
agreements with healthcare professionals and healthcare institutions; as well as any transfers 
of values on the Ministry of Health dedicated website: https://www.entreprises-
transparence.sante.gouv.fr.   
  
12.4 
Protocol amendment(s) 

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Neither the physician nor CPF is permitted to amend the study protocol without obtaining the 
written agreement of the other party. Once the study has started, amendments should only be 
made in exceptional circumstances. The amendments then become an integral part of the 
study protocol. 
In accordance with local laws, the competent authorities will be informed of any subsequent 
amendment to the protocol. 
Any significant change relating to the protocol will be the subject of a written report, including 
a description of the reasons for this change, particularly those made in relation to the quality 
of the study or at the request of the Sponsor or study Scientific Committee. 
The amendments made to the study protocol will be submitted for an opinion to the French 
Ethics Committee. 
 
12.5 
Information for patients and confidentiality of the collected data 
Before entering the study, the physician must inform the patient, using a vocabulary that the 
patient can understand, of the nature and objective(s) of the study and of the right to object to, 
access and correct his/her data. The physician will give the patient an information form. 
The physician must ensure that the confidentiality of the patient data is strictly maintained and 
that their identity is protected from unauthorised parties. 
The patient data collected in the eCRF and the paper questionnaires will be registered in coded 
form. The patients will be identified using a number made up of 4 digits: 3 digits for the 
investigator and 1 digits for the inclusion order number. The physician will maintain a patient 
identification table with patient’s identity and corresponding study number. The physician will 
be bound by professional secrecy and no one else will have access to it. This table will be 
stored by the physician in a secure manner. At the end of the study, the physician will be 
responsible for destroying this table. Names of patients will never be sent to the sponsor. 
The physician must keep study documents in a safe location.  
It must be possible to find all the information completed in the eCRF in the source data, stored 
in the patient's medical file. 
 
12.6 
Rationale for the use of personal data  
The use of indirectly personally identifiable data is crucial in this study since it will allow quality 
control. Physicians may be requested written corrections for missing or inconsistent data 
essential to the study. 
 
12.7 
Financial agreement with the physicians 
The physician and ITEC Services (appointed by CPF) will sign a specific financial agreement 
prior to the study, detailing all the responsibilities incumbent upon CPF and the physician, in 

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relation to the study. Compensation will be provided for each patient included; the terms and 
conditions of payment will be specified in the financial agreement.  
 
12.8 
Delegation of duties by the physician 
The physician must ensure that all persons collaborating in the study have all the necessary 
information concerning the protocol, any potential amendments, as well as their duties and 
functions in the study. 
 
12.9 
Archiving 
The key documents, as listed below, must be stored by the physician in a secure location that 
allows quick access if necessary. By signing the protocol, the investigator agrees to store these 
for a period of 5 years. However, a longer period could possibly be imposed by new regulatory 
requirements.  
Key documents include, in particular:  
 all the source documents, 
 patient information form  
 the patient identification list (i.e. the list of codes linking each patient number to the patient's 
identity).  
The complete list of essential documents to be stored by the investigator for the purposes of 
the study will be provided by ITEC Services during the study set-up. 
After the end of the study and at the end of the planned storage period, the physician has the 
responsibility to destroy the study documents (including the patient information forms and the 
patient identification list) and to inform the sponsor of this destruction. 
Originals of all the study documents will be stored by CPF, except the patient identification list 
and the originals of the information forms which should never be sent to CPF or ITEC Services.  
 
13 
DOCUMENTATION AND USE OF THE STUDY RESULTS 
13.1 
Documentation of the study results 
13.1.1 
Documents completed by the physician 
ITEC Services, appointed by CPF, will provide each physician, in a timely manner, with a 
sufficient quantity of all the documents needed to collect the study data. 
The physician will enter into the eCRF all data collected from medical files as part of the 
protocol. The method for completing and correcting the eCRFs will be explained to the 
physician during the study initiation. 

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The physician must complete the eCRF as soon as possible after collecting the information, 
and preferably on the day of the visit. 
The physician will also complete a questionnaire as described in Section 5.3.2.   
 
13.1.2 
Documents completed by the patient 
After having been informed of the study by the physician, and if he/she agrees to participate, 
the patient will be asked to complete the 4 self-assessment questionnaires described in 
Section 5.3.2.  
 
13.1.3 
Study report 
ITEC Services will produce a final study report in collaboration with CPF. The complete report 
(statistical and clinical) will be validated by the lead physician for the project at CPF and by the 
study Scientific Committee.  
 
13.2 
Use of the study results 
All the information related to the operations of CPF and as yet unpublished scientific data 
provided by CPF is confidential and remains the sole property of CPF. The physician 
undertakes to use this information solely for the conduct of the study and not for any other 
reason, except with prior written agreement of CPF. 
Any publication of the study results should comply with the publication rules of CPF. 
The results of the study may be published or communicated orally during scientific conferences 
by members of the Scientific Committee after prior agreement has been obtained from CPF 
and the learned societies or cooperative groups that may be involved (scientific partnership).   
In accordance with article L1122-1 of the Public Health Code in France, the patients may ask 
to be informed of the study results by his/her physician. 
 
 
 

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14 
BIBLIOGRAPHICAL REFERENCES  
 
Babigumira, Joseph B., Meng Li, Denise M. Boudreau, Jennie H. Best, et Louis P. Garrison. 
2017. « Estimating the Cost of Illness of Giant Cell Arteritis in the United States ». 
Rheumatology and Therapy 4 (1): 111‑19. https://doi.org/10.1007/s40744-017-0052-
8. 
Bienvenu, B., K. H. Ly, M. Lambert, C. Agard, M. André, Y. Benhamou, B. Bonnotte, et al. 
2016a. « Management of Giant Cell Arteritis: Recommendations of the French Study 
Group for Large Vessel Vasculitis (GEFA) ». La Revue De Medecine Interne 37 (3): 
154‑65. https://doi.org/10.1016/j.revmed.2015.12.015. 
———. 2016b. « Management of Giant Cell Arteritis: Recommendations of the French Study 
Group for Large Vessel Vasculitis (GEFA) ». La Revue De Medecine Interne 37 (3): 
154‑65. https://doi.org/10.1016/j.revmed.2015.12.015. 
Brooks, R. 1996. « EuroQol: The Current State of Play ». Health Policy (Amsterdam, 
Netherlands) 37 (1): 53‑72. 
Dasgupta, Bhaskar, Frances A. Borg, Nada Hassan, Leslie Alexander, Kevin Barraclough, 
Brian Bourke, Joan Fulcher, et al. 2010. « BSR and BHPR Guidelines for the 
Management of Giant Cell Arteritis ». Rheumatology (Oxford, England) 49 (8): 
1594‑97. https://doi.org/10.1093/rheumatology/keq039a. 
EuroQol Group. 1990. « EuroQol--a New Facility for the Measurement of Health-Related 
Quality of Life ». Health Policy (Amsterdam, Netherlands) 16 (3): 199‑208. 
Evans, J. M., W. M. O’Fallon, et G. G. Hunder. 1995. « Increased Incidence of Aortic 
Aneurysm and Dissection in Giant Cell (Temporal) Arteritis. A Population-Based 
Study ». Annals of Internal Medicine 122 (7): 502‑7. 
Kötter, Ina, Jörg C. Henes, Annette D. Wagner, Jan Loock, et Wolfgang L. Gross. 2012. 
« Does Glucocorticosteroid-Resistant Large-Vessel Vasculitis (Giant Cell Arteritis 
and Takayasu Arteritis) Exist and How Can Remission Be Achieved? A Critical 
Review of the Literature ». Clinical and Experimental Rheumatology 30 (1 Suppl 70): 
S114-129. 
Mahr, Alfred D., Juan A. Jover, Robert F. Spiera, César Hernández-García, Benjamin 
Fernández-Gutiérrez, Michael P. Lavalley, et Peter A. Merkel. 2007. « Adjunctive 
Methotrexate for Treatment of Giant Cell Arteritis: An Individual Patient Data Meta-
Analysis ». Arthritis and Rheumatism 56 (8): 2789‑97. 
https://doi.org/10.1002/art.22754. 
McHorney, C. A., J. E. Ware, et A. E. Raczek. 1993. « The MOS 36-Item Short-Form Health 
Survey (SF-36): II. Psychometric and Clinical Tests of Validity in Measuring Physical 
and Mental Health Constructs ». Medical Care 31 (3): 247‑63. 
Mukhtyar, C., L. Guillevin, M. C. Cid, B. Dasgupta, K. de Groot, W. Gross, T. Hauser, et al. 
2009. « EULAR Recommendations for the Management of Large Vessel Vasculitis ». 
Annals of the Rheumatic Diseases 68 (3): 318‑23. 
https://doi.org/10.1136/ard.2008.088351. 
Muratore, Francesco, Giulia Pazzola, Nicolò Pipitone, Luigi Boiardi, et Carlo Salvarani. 
2014. « Large-Vessel Involvement in Giant Cell Arteritis and Polymyalgia 
Rheumatica ». Clinical and Experimental Rheumatology 32 (3 Suppl 82): S106-111. 
PNDS. 2017. « Protocole national de diagnostic et de soins (PNDS): Artérite à Cellules 
Géantes (Horton) », juillet. https://www.has-
sante.fr/portail/jcms/c_2789359/fr/arterite-a-cellules-geantes-horton. 

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Proven, Anne, Sherine E. Gabriel, Carlos Orces, W. Michael O’Fallon, et Gene G. Hunder. 
2003. « Glucocorticoid Therapy in Giant Cell Arteritis: Duration and Adverse 
Outcomes ». Arthritis and Rheumatism 49 (5): 703‑8. 
https://doi.org/10.1002/art.11388. 
Pugnet, Grégory, Laurent Sailler, Jean-Pascal Fournier, Robert Bourrel, Jean-Louis 
Montastruc, et Maryse Lapeyre-Mestre. 2016. « Predictors of Cardiovascular 
Hospitalization in Giant Cell Arteritis: Effect of Statin Exposure. A French 
Population-Based Study ». The Journal of Rheumatology 43 (12): 2162‑70. 
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Rabin, Rosalind, Claire Gudex, Caroline Selai, et Michael Herdman. 2014. « From 
Translation to Version Management: A History and Review of Methods for the 
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Outcomes Research 17 (1): 70‑76. https://doi.org/10.1016/j.jval.2013.10.006. 
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2007). Disponible sur : http://adelf.isped.u-bordeaux2.fr/. » s. d. 
Stone, John H., Micki Klearman, et Neil Collinson. 2017. « Trial of Tocilizumab in Giant-
Cell Arteritis ». The New England Journal of Medicine 377 (15): 1494‑95. 
https://doi.org/10.1056/NEJMc1711031. 
Vandenbroucke, Jan P, Erik von Elm, Douglas G Altman, Peter C Gøtzsche, Cynthia D 
Mulrow, Stuart J Pocock, Charles Poole, James J Schlesselman, et Matthias Egger. 
2007. « Strengthening the Reporting of Observational Studies in Epidemiology 
(STROBE): explanation and elaboration ». Epidemiology (Cambridge, Mass.) 18 (6): 
805‑35. https://doi.org/10.1097/EDE.0b013e3181577511. 
Ware, J. E., et C. D. Sherbourne. 1992. « The MOS 36-Item Short-Form Health Survey (SF-
36). I. Conceptual Framework and Item Selection ». Medical Care 30 (6): 473‑83. 
Webster, Kimberly, David Cella, et Kathleen Yost. 2003. « The Functional Assessment of 
Chronic Illness Therapy (FACIT) Measurement System: Properties, Applications, and 
Interpretation ». Health and Quality of Life Outcomes 1 (décembre): 79. 
https://doi.org/10.1186/1477-7525-1-79. 
Zöller, B., X. Li, J. Sundquist, et K. Sundquist. 2013. « Occupational and Socio-Economic 
Risk Factors for Giant Cell Arteritis: A Nationwide Study Based on Hospitalizations 
in Sweden ». Scandinavian Journal of Rheumatology 42 (6): 487‑97. 
https://doi.org/10.3109/03009742.2013.793777. 
 
 
 
 
 
 
 

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15 
APPENDICES 
15.1 
Appendix 1: 36-Item Short Form Survey Instrument (SF-36)  
 
 
 

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15.2 
Appendix 2: EuroQol-5 Dimensions - 3 Level version (EQ-5D-3L)  
 
 

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15.3 
Appendix 3: FACIT Fatigue Scale  
 
 
 
15.4 
Appendix 4: Global Arteritis Activity Scale (VAS) 
Could you please indicate the arteritis activity by placing a vertical mark on the line between 
"no disease activity" and "maximum disease activity"? 
 
 
 
 
 
 
Maximum disease 
activity 
No 
disease 
activity