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Prognostic Evaluation of Inflammatory Polyarthritis of Recent Onset (EUPA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00512239
Recruitment Status : Recruiting
First Posted : August 7, 2007
Last Update Posted : April 25, 2019
The Arthritis Society, Canada
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Gilles Boire, Université de Sherbrooke

Brief Summary:

Inflammatory joint diseases are major causes of invalidity and morbidity. Rheumatoid arthritis (RA), the most frequent of chronic arthritides, affects close to 1% of the Canadian population. Direct and indirect costs of RA represent close to 1% of the gross national product. Recent evidence suggest that initiation of early (e.g., during the first 3-12 months of disease) aggressive treatment decreases both mortality and long term invalidity in RA and other chronic arthritides. However, a significant proportion of patients with early polyarthritis (EPA) have a benign evolution, even if they fulfill criteria for RA. On the contrary, most patients whose arthritis persist for more than 12 months have a progressive and destructive disease. Currently available clinical, serological and genetic markers of severity in arthritic patients perform poorly in EPA patients to identify those patients whose arthritis is likely to persist and thus who deserve an aggressive treatment.

The Investigators propose a prospective and longitudinal study to define the contribution of detection of rheumatoid arthritis-specific autoantibodies (RASA), either alone or in combination with other markers of severity, in the prognostic evaluation of patients presenting with EPA. Availability of such an effective serological tool to establish prognosis in individual patients would improve therapeutic decisions in clinical practice. The same prognostic tools would represent very powerful instruments to subset patients into more homogeneous groups in clinical trials, increasing their power.

Condition or disease
Rheumatoid Arthritis Inflammatory Arthritis

Detailed Description:

Inflammatory polyarthritides are major causes of invalidity and morbidity. Treatment of rheumatoid arthritis (RA), the most common and most severe of these diseases, is clearly more effective when initiated early using aggressive therapeutic protocols. The recent availability of very effective but extremely costly biologic agents may further improve our treatment strategies. Specific arthritides (e.g., RA) were defined using sets of criteria that are unable to define prognosis and cannot be used to select which patients, early in the course of their disease, should be treated aggressively. A number of putative prognostic markers of severity are available, including anti-Sa and anti-Cyclic Citrullinated peptides (Anti-CCP) antibodies (Abs), whose presence is highly specific to RA. Anti-Cit Abs might characterize one of the severe subsets of RA, both clinically and pathogenically. However, these markers are not yet demonstrated to risk-stratify patients with arthritis of recent onset.

Objectives. Our PRIMARY objectives are to evaluate the sensitivity, specificity, and positive likelihood ratios (+LR) of anti-Sa Abs to identify among patients with early polyarthritis (EPA) in the first 12 months of disease (median 4 months) those that will, at 18, 30, 42 and 60 months into disease : 1- have persistent arthritis; 2- satisfy American College of Rheumatology (ACR) criteria for RA; 3- have developed a SEVERE disease (as defined by their Sharp/van der Heijde radiological score or their modified Health Assessment Questionnaire (M-HAQ) score, as well as by our composite index that includes both scores).

In particular, we want to evaluate the size of the ADDITIONAL independent contribution of anti-Sa Abs to predict severe disease, when added to markers of poor prognosis in established RA (e.g., immunoglobulin M (IgM) Rheumatoid Factor (RF), "shared epitope", persistent high C-Reactive Protein (CRP) levels).

Our SECONDARY objectives are to evaluate the sensitivity, specificity, and +LR : 1- of anti-CCP and anti-Sa Abs (individually and in sets) to identify among patients with EPA those who will develop a SEVERE disease after 18, 30, 42, and 60 months; 2- of novel genetic markers to identify among patients with EPA those that will develop a SEVERE disease after 18, 30, 42, and 60 months; 3- of anti-Sa and anti-CCP Abs to identify among patients with EPA those patients who will require more intensive anti-rheumatic treatment (DMARD combinations and/or biologics) at 18, 30, 42 and 60 months; and 4- of serum and urine markers of cartilage degradation and regeneration to identify among patients with EPA those that will develop a SEVERE disease after 18, 30, 42, and 60 months.

Methods. We set up a single-center longitudinal observational study (LOS) planned to include 390 consecutive EPA patients observed over 5 years. EPA is defined as synovitis affecting 3 or more joints for more than one month and less than 12 months, with few specific exclusions. At inclusion, and at each pre-defined time points after disease onset, extensive (but focused) demographic, clinical, serological, radiological and genetic data are collected, without interference with their treatment. Treating physicians and patients remain uninformed about the status of the patients regarding research data (genomic data, anti-Sa and anti-CCP Abs). About 250 such patients will have been included at the time of renewal. Loss to follow up (up to V4 in some patients) at each visit is about 5% and is mostly found in patients in remission. Data collected are used to verify whether patients have reached predefined outcomes including remission, persistence of arthritis, persistence of arthritis fulfilling RA criteria, DMARD use, and SEVERE disease.

Discussion. We have now assembled a large cohort of patients with EPA that are thoroughly reassessed at regular intervals, allowing stratification of patients using outcome measures that have been set in advance. The information gained from this study may have very significant therapeutic and economic implications.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: Early Prediction of Patient-related and Radiological Outcomes in Patients With Recent-onset Inflammatory Polyarthritis (EPA) Using Established and Novel Independent Predictors
Actual Study Start Date : November 1999
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : September 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

EUPA cohort
Consecutive adult patients presenting to receive rheumatological care at the Sherbrooke University Hospital Centre (CHUS) with an immune-mediated inflammatory arthritis affecting at least 3 joints for a duration of more than 4 and less than 52 weeks.

Primary Outcome Measures :
  1. Role of anti-Sa antibodies as predictor of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months after symptom onset ]

Secondary Outcome Measures :
  1. Role of psychosocial determinants as predictors of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months ]

Other Outcome Measures:
  1. Genetic and epigenetic predictors of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months from symptom onset ]

Biospecimen Retention:   Samples With DNA
Serum, genomic DNA and RNA from peripheral blood, PBMC used for in vitro osteoclastogenesis

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with recent-onset inflammatory polyarthritis with an immune cause (excluding infection, crystal-induced) and without characteristics diagnostic for connective tissue diseases or systemic vasculatidies

Inclusion Criteria:

  • Early Rheumatoid arthritis
  • Early Inflammatory Arthritis

Exclusion Criteria:

  • Refusal or inability to consent
  • Infectious arthritis
  • Microcrystalline arthritis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00512239

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Contact: Gilles Boire, MD, MSc (819) 564-5261

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Canada, Quebec
Centre hospitalier universitaire de Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1H 4N4
Contact: Gilles Boire, MD, MSc    (819) 564-5261   
Sponsors and Collaborators
Gilles Boire
The Arthritis Society, Canada
Canadian Institutes of Health Research (CIHR)
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Principal Investigator: Gilles Boire, MD, MSc Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Additional Information:

Publications of Results:

Other Publications:
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Responsible Party: Gilles Boire, MD, Université de Sherbrooke Identifier: NCT00512239    
Other Study ID Numbers: EUPA97-04
CIHR MOP-110959 ( Other Grant/Funding Number: Canadian Institutes for Health Research )
First Posted: August 7, 2007    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Anonymized data to be shared following individual agreements
Keywords provided by Gilles Boire, Université de Sherbrooke:
Early Rheumatoid Arthritis
Early inflammatory arthritis
Anti-Sa antibodies
Anti-CCP antibodies
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases