Prognostic Evaluation of Inflammatory Polyarthritis of Recent Onset(EUPA)
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.
|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|
- 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 ]
- Role of psychosocial determinants as predictors of severe outcomes [ Time Frame: At 12, 18, 30, 42 and 60 months ] [ Designated as safety issue: No ]
- 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
|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)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00512239
|Contact: Gilles Boire, MD, MSc||(819) 564-5261||Gilles.Boire@USherbrooke.ca|
|Centre hospitalier universitaire de Sherbrooke||Recruiting|
|Sherbrooke, Quebec, Canada, J1H 4N4|
|Contact: Gilles Boire, MD, MSc (819) 564-5261 Gilles.Boire@USherbrooke.ca|
|Principal Investigator:||Gilles Boire, MD, MSc||Centre Hospitalier Universitaire de Sherbrooke|