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Rheumatoid ArthritisEUPANCT00512239

Prognostic Evaluation of Inflammatory Polyarthritis of Recent Onset

An observational study of Rheumatoid Arthritis and Inflammatory Arthritis, run by Gilles Boire at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Rheumatoid Arthritis, Inflammatory Arthritis
How many people
1,000 participants
Where
1 siteCanada
Study dates
Jul 1998to Dec 2035
How long will I take part?
10 Years
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • Early Rheumatoid arthritis
  • Early Inflammatory Arthritis

Who cannot join

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Gilles Boire, MD, MSc contact

(819) 564-5261

Gilles.Boire@USherbrooke.ca

Canada1 site, 1 recruiting
  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 4N4

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

    Recruiting

Other trials in Canada

About this study

Official title: Early Prediction of Patient-related and Radiological Outcomes in Patients With Recent-onset Inflammatory Polyarthritis (EPA) Using Established and Novel Independent Predictors

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.

Read the 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.

Keywords
Early Rheumatoid Arthritis, Early inflammatory arthritis, Biomarkers, Autoantibodies, Anti-Sa antibodies, Anti-CCP antibodies
Medical subject headings
Arthritis, Rheumatoid, Arthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00512239
Study groupRoleWhat they receive
EUPA cohortConsecutive 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Role of anti-Sa antibodies as predictor of severe radiographical damage

    Proportion of patients who have detectable damage (that is a score of least 5, the minimally detectable difference) on radiographs of hands, wrists and feet according to Sharp score modified by van der Heijde (0-448; higher scores indicative of more damage)

    Measured: At 60 months after symptom onset

Secondary outcomes (3)
  1. Role of anti-Sa antibodies as predictor of the use of advanced therapy

    Proportion of patients who use advanced therapies (biologics and Jak inhibitors) at the time of the visit

    Measured: At baseline and annually over 60 months after symptom onst

  2. Role of anti-Sa antibodies as predictor of persistent disease activity

    Proportion of patients who fail to reach remission in disease activity at the time of the visit according to Simple Disease Activity Index (SDAI; 0.1-96; a higher score means higher disease activity; a score below 3.3 indicates remission)

    Measured: At inclusion and annually over 60 months after symptom onset

  3. Role of psychosocial determinants as predictors of severe outcomes

    Proportion of participants who fail to reach remission at the time of the visit according to Simple Disease Activity Index (SDAI)

    Measured: At baseline and annually over 60 months after symptom onset

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2007 (estimated)
  2. Study startJul 1998
  3. Primary completionDec 2030 (estimated)
  4. Study completionDec 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
1,000 participants (estimated)
Target duration
10 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT00512239
Sponsor's protocol ID
EUPA97-04
Other IDs
CIHR MOP-110959
Acronym
EUPA
Status last verified
Mar 2025
First submitted
6 Aug 2007
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Anonymized data to be shared following individual agreements

Publications

  • Maksymowych WP, Boire G, van Schaardenburg D, Wichuk S, Turk S, Boers M, Siminovitch KA, Bykerk V, Keystone E, Tak PP, van Kuijk AW, Landewe R, van der Heijde D, Murphy M, Marotta A. 14-3-3eta Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis. J Rheumatol. 2015 Sep;42(9):1587-94. doi: 10.3899/jrheum.141385. Epub 2015 Jul 15.

    PubMed 26178283
  • Leblanc-Trudeau C, Dobkin PL, Carrier N, Cossette P, de Brum-Fernandes AJ, Liang P, Masetto A, Boire G. Depressive symptoms predict future simple disease activity index scores and simple disease activity index remission in a prospective cohort of patients with early inflammatory polyarthritis. Rheumatology (Oxford). 2015 Dec;54(12):2205-14. doi: 10.1093/rheumatology/kev272. Epub 2015 Jul 25.

    PubMed 26209789
  • Challener GJ, Jones JD, Pelzek AJ, Hamilton BJ, Boire G, de Brum-Fernandes AJ, Masetto A, Carrier N, Menard HA, Silverman GJ, Rigby WFC. Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis. J Rheumatol. 2016 Feb;43(2):273-281. doi: 10.3899/jrheum.150179. Epub 2015 Dec 15.

    PubMed 26669911
  • Carrier N, Marotta A, de Brum-Fernandes AJ, Liang P, Masetto A, Menard HA, Maksymowych WP, Boire G. Serum levels of 14-3-3eta protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis. Arthritis Res Ther. 2016 Feb 1;18:37. doi: 10.1186/s13075-016-0935-z.

    PubMed 26832367
  • Boire G, Cossette P, de Brum-Fernandes AJ, Liang P, Niyonsenga T, Zhou ZJ, Carrier N, Daniel C, Menard HA. Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis. Arthritis Res Ther. 2005;7(3):R592-603. doi: 10.1186/ar1719. Epub 2005 Mar 17.

    PubMed 15899046
  • Guzian MC, Carrier N, Cossette P, de Brum-Fernandes AJ, Liang P, Menard HA, Boire G. Outcomes in recent-onset inflammatory polyarthritis differ according to initial titers, persistence over time, and specificity of the autoantibodies. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1624-32. doi: 10.1002/acr.20288. Epub 2010 Jul 8.

    PubMed 20617532
  • Carrier N, Cossette P, Daniel C, de Brum-Fernandes A, Liang P, Menard HA, Boire G. The DERAA HLA-DR alleles in patients with early polyarthritis: protection against severe disease and lack of association with rheumatoid arthritis autoantibodies. Arthritis Rheum. 2009 Mar;60(3):698-707. doi: 10.1002/art.24353.

    PubMed 19248090
  • Dobkin PL, Liu A, Abrahamowicz M, Carrier N, de Brum-Fernandes AJ, Cossette P, Boire G. Predictors of pain for patients with early inflammatory polyarthritis. Arthritis Care Res (Hoboken). 2013 Jun;65(6):992-9. doi: 10.1002/acr.21923.

    PubMed 23281243
  • Maksymowych WP, van der Heijde D, Allaart CF, Landewe R, Boire G, Tak PP, Gui Y, Ghahary A, Kilani R, Marotta A. 14-3-3eta is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage. Arthritis Res Ther. 2014 Apr 21;16(2):R99. doi: 10.1186/ar4547.

    PubMed 24751211
  • Jones JD, Hamilton BJ, Challener GJ, de Brum-Fernandes AJ, Cossette P, Liang P, Masetto A, Menard HA, Carrier N, Boyle DL, Rosengren S, Boire G, Rigby WF. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels. Arthritis Res Ther. 2014 Apr 25;16(2):R103. doi: 10.1186/ar4552.

    PubMed 24766912
  • Carrier N, Marrugo J, Paudel ML, Roux S, Allard-Chamard H, de Brum-Fernandes AJ, Liang P, Boire G. Longitudinal changes in patient characteristics as drivers of clinical outcomes in the Early Undifferentiated PolyArthritis (EUPA) cohort. Rheumatology (Oxford). 2026 Jan 8;65(1):keaf650. doi: 10.1093/rheumatology/keaf650.

    PubMed 41358962

Questions about this trial

What is this clinical trial studying?

An observational study of Rheumatoid Arthritis and Inflammatory Arthritis, run by Gilles Boire at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gilles Boire, MD, MSc ((819) 564-5261, Gilles.Boire@USherbrooke.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Role of anti-Sa antibodies as predictor of severe radiographical damage (time frame: At 60 months after symptom onset). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00512239, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.

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