Pos0024 prediction of spontaneous improvement in patient reported outcome scores in osteoarthritis using markers of joint tissue turnover

Background Osteoarthritis (OA) is a chronic disease characterized by pain and disability. There is no modifying treatment approved for OA today. This may be attributed to the difficulty generating a robust response based on patient-reported outcomes (PROs) linked to the drug mode of action. There is a need in drug development to test and validate biomarkers that objectively relate to PROs or even predict changes in PROs. Biomarkers of cartilage and bone turnover are associated with structural and symptomatic progression. 1 In addition, recent findings suggest that a subset of OA patients have elevated serum levels of C-reactive protein metabolites (CRPM), which is predictive of radiographic progression. 2,3 Objectives This explorative study aimed to investigate the association between PROs and markers of joint tissue formation and degradation in patients with either high or low levels of CRPM. In particular, whether levels could predict spontaneous improvement in PROs. Methods 146 knee OA patients, 62% women, from the NYU cohort were included. 4 Mean (SD) age, 62.5 (10.1); BMI, 26.6 (3.6); 32% NSAID users; and 67.6% w. radiographic OA (KL≥2). PROs were recorded at baseline (BL) and 2 years (FU), and the current investigation was: WOMAC pain, stiffness, and function. The mean (SD) for WOMAC pain, stiffness, and function were 35.4 (22.9), 40.8 (25.7), and 41.7 (28.3) mm on a 100 mm scale. Twenty-one healthy individuals were included as a reference. Eight serum biomarkers of type I, II, III, and IV collagen degradation (C1M, C2M, C3M, C4M) and formation (PRO-C1, PRO-C2, PRO-C3, and PRO-C4) as well as the inflammatory biomarker CRPM, were assessed at baseline. LN-transformed data was adjusted for race, Sec, age, BMI, and NSAID use when comparing OA to controls and in the predictive model. Marked symptomatic (S) OA was defined as ≥40 mm in either of the WOMAC scores at BL and improvement as 20 mm decreased in any of the scores from BL to FU. Results There was no difference in mean marker levels between controls and OA patients. Only C2M correlated with the WOMAC scores at baseline in the ALL population (p <0.001). This correlation was maintained in both the high and low CRPM groups. A high correlation was observed between the PROs and PRO-C4, C1M and C3M, but only in the high CRPM group. Next, we investigated whether the markers could predict symptomatic improvement in patients with marked SOA. A combination of C4M, Age and BMI was predictive of pain improvement in the ALL population (Table 1). Interestingly the predictors were different in the low vs. high CRPM group; PRO-C2, PRO-C3, PRO-C4 and Sex predicted a 20 mm decrease in WOMAC pain in the low group, while C2M alone predicted an improvement in the high CRPM group. Moreover, C2M predicted an improvement in stiffness in the CRPM high, but not in the low CRPM group. C1M and C3M predicted a 20 mm decrease in function only in the high CRPM group. Conclusion Levels of the joint tissue markers weew subtle compared to controls. However, the markers, together with sex and BMI, could predict symptomatic improvement. This may provide novel insight into the link between tissue turnover and PROs. References [1]Kraus, V. B. et al. Predictive validity of biochemical biomarkers in knee osteoarthritis: Data from the FNIH OA Biomarkers Consortium. Ann. Rheum. Dis. 76 , 186–195 (2017). [2]Alexander, L. C. et al. A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis. Arthritis Res. Ther. 23 , 226 (2021). [3]Bay-Jensen, A. C. et al. Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis. Sci. Rep. 11 , (2021). [4]Attur, M. et al. Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis. Osteoarthr. Cartil. 23 , 1915–1924 (2015). Disclosure of Interests Mukundan Mukundan: None declared, Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, Jonathan Samuels: None declared, Morten Karsdal Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, Steven Abramson: None declared