MedicalResearch.com Interview with:
Pr Gilles Boire, M.D., M. ScService de rhumatologie
Département de médecine
Faculté de médecine et des sciences de la santé
Université de Sherbrooke
MedicalResearch.com: What is the background for this study?
Response: Rheumatoid arthritis (RA) patients are heterogeneous at initial presentation, in response to treatments and according to their outcomes. No clinical features and very few biomarkers, except autoantibodies such as anti-Cyclic Citrullinated Peptides/Proteins (CCP), identify patients with divergent prognostic trajectories.
To help improve early prognostic classification, we initiated 20 years ago the single center longitudinal observational Early Undifferentiated PolyArthritis (EUPA) study of consecutive patients presenting with recent-onset inflammatory polyarthritis, 90% of which fulfill classification criteria for RA at baseline. Our registry includes 739 very early RA patients (median symptom duration 3.6 months), rapidly treated to joint remission (i.e. 0/66 swollen joint) and followed over 5 years. Each patient visit is linked to biosamples and to sequential radiographs scored according to the modified Sharp/van der Heijde method. As we had the clinical impression that clinical features of recruited patients were evolving, we compared patients from 3 periods (1998-2004; 2005-2010; 2011-2017).
MedicalResearch.com: What are the main findings?
Response: Our main observations include a constant decrease of current smoking (from 22.4 to 12.3%), paralled by a constant decrease in titers of IgM Rheumatoid Factor (RF) and anti-CCP2 antibodies, translating into a very significant decrease of RF positivity (47.8 to 36.7%) and a decrease of seropositive (either Rheumatoid Factor (RF) or anti-CCP2) patients from 53.5 to 44.1% over these 20 years. Globally, the patients reported a decrease in the impact of disease (Patient Global Assessment of Disease activity) and lower levels of acute phase reactants, translating into lower Simple Disease Activity Index (SDAI) scores. Interestingly, the prevalence of HLA DR shared epitope (62.2-64.9%), current smoking (18.8-25.3%), concomitant comorbidities (cardiovascular 33.0-40.7%; cancer 3.0-6.2%) and RF positivity (79.0-86.0%) was not different among anti-CCP2 positive patients across different periods. However, among anti-CCP2 negative patients, current smoking (20.6 to 8.6%) and RF positivity (21.4 to 13.5%) significantly decreased while cardiovascular (44.8% to 59.5%) and cancer (4.1 to 12.8%) comorbidities increased. Shared epitope prevalence was consistently similar to or lower among seronegative patients (30.3 to 41.7%) than among population controls (38.4%).
MedicalResearch.com: What should readers take away from your report?
Response: In the recent years, compared to previous decades, patients presenting with a clinical diagnosis of RA are more and more likely to be seronegative (especially for RF); they also present with lower (and frequently normal) levels of acute phase reactants and with lower scores of disease activity, but with an increasing prevalence of cardiovascular and cancer comorbidities. The decrease in seropositive RA appears to parallel the decrease in current smoking, while the increase in seronegative RA occurs in slightly older patients with more evidence of pre-existent comorbidities, suggesting the impact of distinct mediators of disease contributing to immune senescence.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The major focus of research on seropositive RA during the last decades has revealed a strong link between genetics (HLA DR shared epitope) and the environment (mostly tobacco smoking) translating into the production of autoantibodies and typical features of seropositive RA. The currently used treatment strategies were developed for, and mostly shown to be effective among seropositive RA patients.
A similar level of investment in research on seronegative RA is now required, in order to delineate new biomarkers of the disease and to address the immune senescence that appears to contribute to seronegative RA development, together with other chronic diseases.
Disclosures: Bristol Myers Squibb Canada (BMS) funded this specific analysis.
The EUPA study was designed and performed by Sherbrooke rheumatologists without any input from third parties, including BMS. Funding for EUPA was obtained from public granting agencies, including The Arthritis Society and the Canadian Institutes for Health Research (CIHR). This specific analysis was performed in Sherbrooke by EUPA personnel without any sharing of individual data with third parties, including BMS.
ACR/ARPH 2018 ABSTRACT NUMBER: 2983
Nathalie Carrier1, Sophie Roux2, Ariel Masetto2, Artur J deBrum Fernandes3, Patrick Liang4, Meryem Maoui5 and Gilles Boire
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