Study and Monitoring of Early Undifferentiated Arthritis (ESPOIR)

• ClinicalTrials.gov Identifier: NCT03666091
• Recruitment Status: Active, not recruiting
• First Posted: September 11, 2018
• Last Update Posted: October 26, 2022
• Sponsor: Societe Francaise de Rhumatologie
• Collaborators: Amiens University Hospital; University Hospital, Bordeaux; University Hospital, Brest; University Hospital, Lille; University Hospital, Montpellier; Saint Antoine University Hospital; Pitié-Salpêtrière Hospital; Hôpital Cochin; Bicetre Hospital; Bichat Hospital; University Hospital, Rouen; University Hospital, Strasbourg, France; University Hospital, Toulouse; University Hospital, Tours
• Information provided by (Responsible Party): Societe Francaise de Rhumatologie

Tracking Information

• First Submitted Date: August 31, 2018
• First Posted Date: September 11, 2018
• Last Update Posted Date: October 26, 2022
• Actual Study Start Date: November 13, 2002
• Actual Primary Completion Date: April 19, 2005 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2021)

• Remaining in the cohort. [ Time Frame: 20 years ]
  Presence of the patient at the visit.
• Prescription of synthetic or biologic disease-modifying antirheumatic drugs (DMARD). [ Time Frame: 20 years ]
  Number of patients treated or not.
• Patient disability evaluation. [ Time Frame: 20 years ]
  Evaluation by Health Assessment Questionnaire Disability Index (HAQ-DI). The following categories are assessed by the HAQ-DI: dressing and grooming, arising, eating, walking, hygiene, reach, grip, common daily activities. The patients report the amount of difficulty they have in performing some of these activities. Each question asks on a scale ranging from 0 to 3. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment.
• Change in Disease Activity (levels of activity or remission) [ Time Frame: 20 years ]
  1. Disease Activity Score (DAS28). The DAS28 provides an absolute indication of RA disease activity on a scale of 0.49 to 9.07 A DAS28 value >5.1 corresponds to a high disease activity, A DAS28 value between 3.2 and 5.1 corresponds to a moderate disease activity, A DAS28 value between 2.6 and 3.2 corresponds to a low disease activity, A DAS28 value < 2.6 corresponds to remission.
  2. Physician and patient activity VAS. Scales from 0 to 100. A high value indicates extreme activity.
• Quality of life assessed by EQ-5D-3L/ EUROQOL [ Time Frame: 20 years ]
  The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems.The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The EQ VAS records the respondent's self-rated health (0-100).
• Quality of life assessed by MOS-SF-36/ MOS 36-Item Short-Form Health Survey [ Time Frame: 15 years (from baseline to 15 years) ]
  MOS-SF-36/ MOS 36-Item Short-Form Health Survey contains 8 health concepts: 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. It also includes a single item that provides the perceived change in health. Each dimension has a scale (0-100). Low score=poor quality of life.
• Quality of life assessed by AIMS2-SF/Arthritis Impact Measurement Scales 2 Short Form [ Time Frame: 14 years (from baseline to 14 years) ]
  AIMS2-SF/Arthritis Impact Measurement Scales 2 Short Form contains 26 items : upper-extremity functioning, lower-extremity functioning, affect, symptoms, social interaction, and role. Scores are summed and converted to a range of 0-10. Higher scores=poorer health.
• Radiographic damage evaluation [ Time Frame: 20 years ]
  Structural joint damage was assessed radiographically and expressed as change in Total Sharp Score (TSS) and its components.The SHS method evaluates, in each hand, 16 areas for erosions and 15 areas for JSN, and, in each foot, 6 areas for erosions and 6 areas for JSN. The erosion score per hand joint can range from 0 to 5. JSN and joint subluxation or luxation are combined in a single score, from 0 to 4. The maximal score for erosion and JSN are 160 and 120, respectively, for the hands and 120 and 48, respectively, for the feet. The maximal total SHS is 448.

Original Primary Outcome Measures (submitted: September 7, 2018)

• Remaining in the cohort [ Time Frame: 20 years ]
  Presence of the patient at the visit
• Prescription of synthetic or biologic disease-modifying antirheumatic drugs (DMARD) [ Time Frame: 20 years ]
  Number of patients treated or not
• Patient disability evaluation [ Time Frame: 20 years ]
  Evaluation by Health Assessment Questionnaire (HAQ)
• Change in Disease Activity (levels of activity or remission) [ Time Frame: 20 years ]
  Disease Activity Score (DAS28)
• Change in Disease Activity (levels of activity or remission) [ Time Frame: 20 years ]
  Physician and patient activity VAS
• Quality of life evaluation [ Time Frame: 20 years ]
  Evaluation by EQ5D
• Quality of life evaluation [ Time Frame: 20 years ]
  Evaluation by SF-36
• Quality of life evaluation [ Time Frame: 20 years ]
  Evaluation by AIMS2-SF
• Radiographic damage evaluation [ Time Frame: 20 years ]
  Structural joint damage was assessed radiographically and expressed as change in Total Sharp Score (TSS) and its components.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study and Monitoring of Early Undifferentiated Arthritis
• Official Title: Etude et Suivi Des POlyarthrites Indifférenciées Récentes

Brief Summary

The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, ESPOIR, in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis.

The primary objective is to set-up a multicentre cohort of early arthritis (less than 6 months) in France that could serve as a database to studies of various natures.

Specific objectives are in the following domains:

• diagnosis: to help determine among clinical, biological, radiographic and immunogenetics those parameters allowing for the earliest diagnosis classification as possible, in order to target early therapy;
• prognosis: to identify early those patients at risk of severe disease by investigating among clinical, biological, genetic and sociologic factors;
• medico-economic: to identify the costs and their determinants at various disease stage;
• pathologic: to collect a databank of sera, DNA, RNA to allow for studies of transcriptomes and other genomics.

Secondary objectives are twofold:

• to monitor adverse events, particularly rare drug adverse events, in collaboration with other international studies
• to allow access to the data collected in this cohort study in order to facilitate new projects submitted to and approved by the scientific committee.

Detailed Description

All patients were referred to each regional center every 6 months during the first 2 years, then every year. Procedures were set up to avoid patients lost to followup as much as possible. At baseline and at each visit, we recorded data for a set of clinical and biological variables recommended for the management of early arthritis. At each visit, rheumatoid arthritis was classified according to the 1987 American College of Rheumatology (ACR) criteria and retrospectively to the 2010 ACR/European League Against Rheumatism (EULAR) criteria.

At each visit, patients completed function and quality-of-life self-administered questionnaires including the Health Assessment Questionnaire-Disability Index (HAQ-DI), Arthritis Impact Measurement Scales version 2 short form, a medico economic questionnaire, and globally assessed disease, pain at rest and pain during motion on a visual analog scale (VAS). Patients underwent radiographs of the hand and wrist (face) and foot (face and oblique). Radiographs were stored in the radiological coordinating center (Brest) and then were evaluated by the van der Heijde-modified Sharp score. Serum, DNA, urine, were collected at baseline. Serum and urine were also obtained at each follow-up visit. They were then sent and stored in adequate and definite conditions in the biological coordinating centre (Paris-Bichat).

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Serum at baseline, 6, 12, 18, 24, 36, 60, 120, 180 and 240 months / Urine at baseline, 24 and 36 months / DNA

• Sampling Method: Non-Probability Sample
• Study Population: A total of 814 patients with early arthritis were included be- tween November 2002 and april 2005.One patient removed his consent form. All the centres were active and each regional centre recruited between 35 and 83 patients.
• Condition: Early Rheumatoid Arthritis or Early Undiffentiated Arthritis
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• Vittecoq O, Guillou C, Hardouin J, Gerard B, Berenbaum F, Constantin A, Rincheval N, Combe B, Lequerre T, Cosette P. Validation in the ESPOIR cohort of vitamin K-dependent protein S (PROS) as a potential biomarker capable of predicting response to the methotrexate/etanercept combination. Arthritis Res Ther. 2022 Mar 21;24(1):72. doi: 10.1186/s13075-022-02762-5.
• Kumaradev S, Roux C, Sellam J, Perrot S, Pham T, Dugravot A, Molto A. Socio-demographic determinants in the evolution of pain in inflammatory rheumatic diseases: results from ESPOIR and DESIR cohorts. Rheumatology (Oxford). 2022 Apr 11;61(4):1496-1509. doi: 10.1093/rheumatology/keab562.
• Roubille C, Coffy A, Rincheval N, Dougados M, Flipo RM, Daures JP, Combe B. Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis. Rheumatology (Oxford). 2021 Aug 2;60(8):3738-3746. doi: 10.1093/rheumatology/keaa850.
• Valdeyron C, Soubrier M, Pereira B, Constantin A, Morel J, Gaudin P, Combe B, Gremeau AS, Dejou-Bouillet L, Pouly JL, Sapin V, Oris C, Brugnon F. Impact of disease activity and treatments on ovarian reserve in patients with rheumatoid arthritis in the ESPOIR cohort. Rheumatology (Oxford). 2021 Apr 6;60(4):1863-1870. doi: 10.1093/rheumatology/keaa535.
• Mouterde G, Gamon E, Rincheval N, Lukas C, Seror R, Berenbaum F, Dupuy AM, Daien C, Daures JP, Combe B. Association Between Vitamin D Deficiency and Disease Activity, Disability, and Radiographic Progression in Early Rheumatoid Arthritis: The ESPOIR Cohort. J Rheumatol. 2020 Nov 1;47(11):1624-1628. doi: 10.3899/jrheum.190795. Epub 2019 Dec 15.
• Lukas C, Mary J, Debandt M, Daien C, Morel J, Cantagrel A, Fautrel B, Combe B. Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: data from the ESPOIR cohort. Arthritis Res Ther. 2019 Nov 15;21(1):243. doi: 10.1186/s13075-019-2020-x.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 7, 2018): 813
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2025
• Actual Primary Completion Date: April 19, 2005 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• patients aged over 18 and under 70
• clinical diagnosis of rheumatoid arthritis as certain or probable
• clinical diagnosis of undifferentiated arthritis potentially becoming rheumatoid arthritis
• at least 2 inflammatory joints since 6 weeks : a swollen joint has to be observed in two articular sites and be present since at least 6 weeks
• arthritis starting since less than 6 months
• never prescribed DMARDS, corticoids, except if less than 2 weeks or except intra-articular injection less than 6 weeks before inclusion
• corticosteroids could be tolerated if prescribed for duration less than 2 weeks in the month before the inclusion with an average dose less than 20 mg per day and stopped two weeks before inclusion

Exclusion Criteria:

• patients aged less than 18 years or aged more than 70 years
• pregnant women
• undifferentiated rheumatism with no potential chance to become rheumatoid arthritis
• other inflammatory rheumatisms clearly defined

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03666091
• Other Study ID Numbers: P030717
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Societe Francaise de Rhumatologie
• Original Responsible Party: Same as current
• Current Study Sponsor: Societe Francaise de Rhumatologie
• Original Study Sponsor: Same as current

Collaborators

• Amiens University Hospital
• University Hospital, Bordeaux
• University Hospital, Brest
• University Hospital, Lille
• University Hospital, Montpellier
• Saint Antoine University Hospital
• Pitié-Salpêtrière Hospital
• Hôpital Cochin
• Bicetre Hospital
• Bichat Hospital
• University Hospital, Rouen
• University Hospital, Strasbourg, France
• University Hospital, Toulouse
• University Hospital, Tours

Investigators

• Principal Investigator: Bernard COMBE, MD, PHD; Montpellier University Hospital rheumatology department

• PRS Account: Societe Francaise de Rhumatologie
• Verification Date: October 2022