Prognostic Evaluation of Inflammatory Polyarthritis of Recent Onset(EUPA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Université de Sherbrooke
Sponsor:
Collaborators:
The Arthritis Society, Canada
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Gilles Boire, Université de Sherbrooke
ClinicalTrials.gov Identifier:
NCT00512239
First received: August 6, 2007
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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.

We 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
Rheumatoid Arthritis
Inflammatory Arthritis

Study Type: Observational [Patient Registry]
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Université de Sherbrooke:

Primary Outcome Measures:
  • Role of anti-Sa antibodies as predictor of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months after symptom onset ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Role of psychosocial determinants as predictors of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Genetic and epigenetic predictors of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months from symptom onset ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum, genomic DNA and RNA from peripheral blood, PBMC used for in vitro osteoclastogenesis


Estimated Enrollment: 1000
Study Start Date: November 1999
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
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 ACR criteria for RA; 3- have developed a SEVERE disease (as defined by their Sharp/van der Heijde radiological score or their 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., IgM RF, "shared epitope", persistent high 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. Preliminary analysis of a subset of 136 patients at 18 months shows that anti-Sa Abs present at inclusion give the highest +LR (2 to 4 X) for pre-defined severe disease outcomes. Positive LR of that magnitude are likely to be helpful in the clinical evaluation of an individual EPA patient.

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.

  Eligibility

Ages Eligible for Study:   16 Years to 90 Years
Genders Eligible for Study:   Both
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

Criteria

Inclusion Criteria:

  • Early Rheumatoid arthritis
  • Early Inflammatory Arthritis

Exclusion Criteria:

  • Refusal or inability to consent
  • Infectious arthritis
  • Microcrystalline arthritis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512239

Contacts
Contact: Gilles Boire, MD, MSc (819) 564-5261 Gilles.Boire@USherbrooke.ca

Locations
Canada, Quebec
Centre hospitalier universitaire de Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1H 4N4
Contact: Gilles Boire, MD, MSc    (819) 564-5261    Gilles.Boire@USherbrooke.ca   
Sponsors and Collaborators
Gilles Boire
The Arthritis Society, Canada
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Gilles Boire, MD, MSc Centre Hospitalier Universitaire de Sherbrooke
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilles Boire, MD, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT00512239     History of Changes
Other Study ID Numbers: EUPA97-04, CIHR MOP-110959
Study First Received: August 6, 2007
Last Updated: October 30, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Université de Sherbrooke:
Early Rheumatoid Arthritis
Early inflammatory arthritis
Biomarkers
Autoantibodies
Anti-Sa antibodies
Anti-CCP antibodies

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014