AB0758 CIRCULATING ADIPOKINES AND RESPONSE TO TREATMENT IN EARLY RHEUMATOID ARTHRITIS – DATA FROM THE RANDOMIZED NORD-STAR TRIAL
Authors: G. K. Vasileiadis, Y. Zhang, T. Fatima, R. F. Van Vollenhoven, J. Lampa, B. Gudbjornsson, D. Nordström, G. Grondal, K. Hørslev-Petersen, K. Lend, M. S. Heiberg, M. Lund Hetland, M. Nurmohamed, T. Uhlig, T. Sokka-Isler, A. Rudin, C. Maglio
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Adiponectin, leptin, and resistin are adipokines whose circulating levels are increased in people with rheumatoid arthritis (RA) compared to healthy controls. A few studies in small cohorts have investigated the role of these adipokines as biomarkers of response to anti-rheumatic treatment in RA, with inconsistent results. <h3>Objectives:</h3> We aimed to determine if baseline levels of adiponectin, leptin, and resistin are associated with future response to anti-rheumatic treatment in people with untreated early RA. <h3>Methods:</h3> This post-hoc analysis of the NOrdic Rheumatic Diseases Strategy Trials and Registries (NORD-STAR) trial included data from 341 individuals from Sweden with untreated newly diagnosed RA (1, 2). Participants were randomized at baseline into 4 treatment arms: methotrexate combined with prednisolone (1), certolizumab (2), abatacept (3), or tocilizumab (4). Participants were followed for up to 48 weeks. Clinical and laboratory measurements were performed at baseline, and at 8-, 12-, 24-, and 48-week follow-up. Adipokines were measured in plasma at baseline with ELISA. The primary outcome for this report is the difference in remission according to the Clinical Disease Activity Index (CDAI ≤2.8) over time up to 48 weeks stratified by median adipokine levels. <h3>Results:</h3> As illustrated in Table 1, at baseline, participants with adiponectin levels above the median had lower BMI, higher age, and were more frequently women, whereas participants with leptin levels above the median had a higher BMI and were more frequently women. Baseline levels of adiponectin and leptin were not associated with markers of RA activity (Table 1). At baseline, participants with higher resistin levels had higher c-reactive protein (CRP) levels (29±36 vs 17±22 mg/L; p&lt;0.001), swollen joint count (9±5 vs 8±5; p=0.03), and higher Disease Activity Score of 28 joints based on CRP (5.3±1.0 vs 5.0±1.1; p=0.03) compared to participants with lower resistin (Table 1). Participants with baseline adipokine levels above the median and those with adipokine levels below the median had similar mean CDAI and changes in CDAI throughout follow-up for up to 48 weeks (Figure 1A and B). Kaplan-Meier curves for CDAI remission showed no difference in the likelihood of achieving remission between participants with high vs low adiponectin and those with high vs low resistin at baseline (Figure 1C). Participants whose baseline leptin levels were above the median had a reduced likelihood of achieving remission compared to those whose baseline leptin levels were below the median (Figure 1C). However, cox proportional hazards models adjusted for sex, baseline age, body mass index (BMI), smoking, and CDAI did not show any effect of baseline adiponectin, leptin, and resistin levels on the likelihood of achieving CDAI remission (adiponectin: HR 1.08, 95% CI 0.80-1.45, p=0.62; leptin: HR 0.89, 95% CI 0.64-1.26, p=0.52; resistin: HR 0.86, 95% CI 0.65-1.13, p=0.26). <h3>Conclusion:</h3> Baseline adiponectin, leptin, and resistin levels are not associated with the likelihood of achieving CDAI remission over 48 weeks in this large trial of first-line treatments in early RA. Our results underscore the importance of adjusting for confounders when studying the effects of adipokines on RA outcomes, as circulating adipokine levels are highly dependent on other factors, such as BMI and sex. <h3>REFERENCES:</h3> [1] Hetland ML, et al. BMJ (Clinical research ed). 2020;371:m4328. [2] Østergaard M, et al. Ann Rheum Dis. 2023;82(10):1286-95. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Georgios K. Vasileiadis: None declared, Yuan Zhang: None declared, Tahzeeb Fatima: None declared, Ronald F. van Vollenhoven: None declared, Jon Lampa: None declared, Bjorn Gudbjornsson Lectures fees from Novartis and Nordic Pharma, Consulting fee from Novartis, Dan Nordström Personal consultancy fees from BMS, Lilly, MSD, Novartis, Pfizer and UCB, Personal study grant from MSD, outside current work, Gerdur Grondal: None declared, Kim Hørslev-Petersen: None declared, Kristina Lend: None declared, Marte S Heiberg: None declared, Merete Lund Hetland Research grants from AbbVie, iogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk to institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz paid to institution; participation on a Data Safety Monitoring Board or Advisory Board from Abbvie paid to institution. Chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. Co-chair of EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylarthritis based on secondary data and is partly funded by Novartis., Michael Nurmohamed: None declared, Till Uhlig Personal fees from Galapagos, Lilly, Pfizer, UCB outside the submitted work., Tuulikki Sokka-Isler Research grant from Amgen paid to the institution, honoraria from Nordic Pharma, Anna Rudin: None declared, Cristina Maglio: None declared.