POS0374 CLINICAL IMPACT OF SIGNS OF CALCIUM PYROPHOSPHATE DEPOSITION DISEASE (CPPD) ON RADIOGRAPHS OF HANDS AND WRISTS IN A REAL-WORLD COHORT OF PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

Background: Calcium pyrophosphate deposition disease (CPPD) is a common cause of arthropathy over the age of 60. Although most often presenting as acute mono- or oligoarticular arthritis, CPPD can also manifest as a chronic polyarticular disease. Chronic CPPD diagnosis is frequently uncertain, and may be mistaken for seronegative rheumatoid arthritis (RA), particularly in populations with multiple concurrent causes of arthralgia. Only two retrospective cohort studies [1, 2] have addressed the prevalence of CPPD in RA cohorts and the clinical evolution of these patients. However, neither study examined the potential role of specific hand joint narrowing in CPPD diagnosis or treatment response. Objectives: We aimed to explore whether, in a cohort of patients with early non erosive RA, the presence of specific hand and wrist joint narrowing suggestive of CPPD is associated with specific epidemiological, clinical, serological and radiological features and whether it influences clinical outcomes over the first 60 months. Methods: We retrospectively analyzed data from all RA patients enrolled in the Early Undifferentiated Polyarthritis (EUPA) [3] cohort between July 1998 and November 2023. EUPA inclusion criteria required a baseline SJC66 ≥ 3 and a symptom duration of one to twelve months. Patients with confirmed crystal-induced arthritis, connective tissue disease or vasculitis were excluded. For this analysis, only patients fulfilling the 1987 and/or 2010 RA classification criteria were included, while those with at least one erosion on hand and foot radiographs, as determined by the Sharp-van der Heijde score, were excluded. Baseline and final visit (if available) radiographs of hands and wrists were reviewed by two independent evaluators for confirmation in patients with at least one narrowing suggestive of CPPD (i.e., bilateral radiocarpal, second or third metacarpophalangeal (MCP), scaphotrapeziotrapezoid (STT) joints without first carpometacarpal (CMC) involvement) or chondrocalcinosis, and no typical RA erosions. Descriptive analyses compared patient characteristics with and without CPPD-suggestive radiological signs. Continuous variables were analyzed using Student's t-test or the Mann-Whitney test, depending on data distribution, while categorical variables were assessed with the Chi-square test or Fisher Exact test. Time-dependent outcomes between CPPD-positive and CPPD-negative groups were evaluated using generalized estimating equations for dichotomous outcomes or linear mixed models with repeated measures. Multivariable models were adjusted for baseline variables, including age, sex, BMI, smoking status, and seropositivity. Results: At baseline, 388 of 966 patients were included, with 70 (18%) exhibiting at least one radiologic sign suggestive of CPPD. Prevalence was numerically higher among seronegative (20%) compared to seropositive patients (15%), but this difference was not statistically significant (p=0.16). Compared to patients without CPPD signs, the CPPD group was older (mean 68.9 vs 55.8 years, p<0.001) and had a higher rate of RDCI score ≥ 1 (72.9% vs. 47.5%, p<0.001). No other baseline differences in sociodemographic, clinical and serological characteristics, patient and physician reported outcomes, or treatments were observed between groups (Table 1). Over 60 months, patients with at least one specific narrowing suggestive of CPPD at baseline were significantly more likely to develop narrowing scores ≥5 (RR 7.86, 95% CI [5.28–11.71], p< 0.001). They were also more likely to have an M-HAQ score ≥1 (RR: 1.43, 95% CI [1.02–2], p=0.04) and an RDCI score ≥1 (RR: 1.44, 95% CI [1.21–1.70], p< 0.001) (Figure 1). However, in multivariable analysis, the significance for HAQ and RDCI outcomes disappeared. No significant differences were observed for other outcomes (i.e. SDAI, CDAI, erosions, SJC66, TJC68, pain and fatigue). These patients were more likely to be on active conventional disease modifying drugs (DMARD) therapy (RR: 1.12, 95% CI [1.04–1.20], p=0.002) and to exhibit a swollen wrist (RR: 1.2, 95% CI [1–1.43], p=0.049) (Figure 1), without differences in other joints. Stratification by seropositivity yielded similar results, though the significance for DMARD use was lost in seropositive patients, as was the significance for wrist swelling in both groups. In multivariable analyses, CPPD-suggestive patients were more intensely treated with csDMARDs and biologics with prednisone (Adjusted RR=1.16 (1.08-1.25), p<0.001) and without prednisone (Adjusted RR=1.17 (1.08-1.26), p<0.001). Exploratory analyses comparing patients with one versus multiple joint narrowings revealed no significant differences. Attempts to apply the 2023 ACR/EULAR classification criteria for CPPD were unsuccessful, as no patients met the classification thresholds. Conclusion: This study suggests that patients with at least one radiologic sign suggestive of CPPD in the hands have a clinical course similar to that of other RA patients, regardless of their seropositivity status. These patients tend to be older and have more comorbidities but appeared to have comparable disease activity and outcomes (except for joint narrowing). However, these patients may require more intensive RA treatment, including prednisone. Radiological signs of CPPD in RA may reflect concomitant or preexisting conditions, but their presence should not deter physicians from managing these patients as typical RA cases. Further research is needed to enhance our understanding of this topic and its clinical implications. REFERENCES: [1] Paalanen K et al. Clin Exp Rheumatol. 2020;38:99-106 [2] Krekeler M et al. RMD Open 2022;8:e002383 [3] Carrier N et al. J Rheumatol. 2024 Nov 1:jrheum.2024-0560 Acknowledgements: We thank the staff rheumatologists Dr. Guylaine Arsenault, Dr. Lyne Bissonnette, Dr. Alessandra Bruns and Dr. Pierre Dagenais for their contribution to the recruitment and follow up of EUPA patients. We also thank our dedicated research assistants Chantal Guillet, Noémie Poirier and Christine Rosa for their long-term contribution to the EUPA study. Funding The EUPA cohort was supported by the Canadian Institutes for Health Research MOP-110959 and by The Arthritis Society Grants 00/201 and RG06/108. AJBF, PL, AM, SR and GB are part of the Centre de recherche clinique du Centre hospitalier universitaire de Sherbrooke (CRCHUS) of the Centre intégré universitaire de santé et de services sociaux de l'Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie-CHUS), which received a team grant from the Fonds de Recherche du Québec – Santé (FRQ-S). Disclosure of Interests: Coralie Tremblay: None declared, Nathalie Carrier: None declared, Hugues Allard-Chamard Abbvie, Amgen, Astrazeneca, BMS, Celltrion, Eli Lilly, Hoffmann-La Roche, Fresenius Kabi, GSK, Janssen Novartis, Mantra Pharma, Pfizer, Sobi, Abbvie, Amgen, Astrazeneca, BMS, Celltrion, Eli Lilly, GSK, Hoffmann-La Roche, Janssen Novartis, Pfizer, Clinical studies: Abbvie, BMS, Daiichi Sankyo, Eli Lilly, Neomed, Novartis, Pfizer, Sanofi, Vielabio, Xencor, Eli Lilly, Fresenius Kabi, Pfizer, Javier Marrugo: None declared, Sophie Roux: None declared, Gilles Boire Orimed Pharma, Viatris Canada, Abbvie Canada, Janssen Canada, Eli Lilly Canada, Mylan Canada, Novartis Canada, Pfizer Canada, Sanofi Canada– Advisory board, Otsuka Canada– Advisory board, Teva Canada, Viatris Canada, Canadian Institutes for Health Research MOP-110959, The Arthritis Society Grant 00/201, The Arthritis Society Grant RG06/108, Fonds de recherche en santé du Québec (FRSQ), BMS Canada – unrestricted research grant, Canadian ArTritis CoHort (CATCH), Biocon Canada– unrestricted research grant, Pfizer Canada– unrestricted research grand, Ariel Masetto: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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