POS0474 ULTRASOUND REMISSION RATES AFTER 1 YEAR ARE HIGH IN EARLY RA PATIENTS ON INDUCTION TREATMENT: RESULTS FROM THE RANDOMIZED NORD-STAR TRIAL
Authors: M. S. Heiberg, Y. Kisten, A. Kazemi, H. Rezaei, E. Af Klint, M. K. A. Ljosa, E. Brodin, D. Stevens, G. Bakland, L. F. Karoliussen, P. Bolton-King, J. Lindqvist, K. Lend, J. Lampa, T. Uhlig, M. Lund Hetland, A. Rudin, D. Nordström, B. Gudbjornsson, M. T. Nurmohamed, M. Østergaard, G. Grondal, T. Sokka-Isler, H. B. Hammer, R. F. Van Vollenhoven, E. Haavardsholm
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The randomized controlled NORD-STAR trial demonstrated remission rates of 40-60% in patients with early rheumatoid arthritis (RA) at 24 and 48 weeks according to the Clinical Disease Activity Index (CDAI) when treated early with methotrexate in combination with prednisolone (active conventional therapy (ACT)), certolizumab pegol (CZP), abatacept (ABA) or tocilizumab (TCZ) (1, 2). However, clinical remission criteria reflect in part subjective measures of pain and well-being and not necessarily inflammatory activity. Ultrasound is an imaging tool that aims to measure joint and tendon inflammation objectively. In the NORD-STAR trial, a subset of patients in Norway and Sweden was assessed by ultrasound of joints and tendons. <h3>Objectives:</h3> To compare ultrasound remission rates at week 48 in patients receiving active conventional treatment versus each of the three biological treatments in early RA and explore the effect of conventional and biological DMARDs on ultrasound-measured inflammation. <h3>Methods:</h3> NORD-STAR is an investigator-initiated, randomized, blinded-assessor study. Treatment-naïve early RA patients with moderate-severe disease activity were randomized 1:1:1:1 to methotrexate combined with: 1) oral prednisolone (tapered quickly; discontinued at week 36); 2) CZP; 3) ABA or 4) TCZ. Patients in Norway (all 5 sites) and at Karolinska University Hospital in Sweden were assessed with ultrasound of joints/tendons and ultrasound scores were calculated according to the USRA9 score, including assessment of 8 joints (MCP 1-3, PIP 2-3, radiocarpal, MTP2-3) and 1 tendon (extensor carpi ulnaris) bilaterally with a 0-3 score for grey scale and power Doppler, respectively. Ultrasound remission was defined as Doppler sum score=0. Remission rates (w48) were assessed without imputation of missing values and compared between treatment arms using logistic regression adjusted for multiple testing by the Dunnett's procedure and adjusted for age, gender, center, anti-CCP status at baseline and baseline value for the dependent variable. <h3>Results:</h3> Of the total of 812 patients in the NORD-STAR trial, 239 patients were included in the ultrasound analyses (Norway n=114, Sweden n=125). Patient characteristics were well balanced across the treatment arms. The patients were representative for the whole NORD-STAR population (1,2). Ultrasound remission rates at week 48 were 74 % for ACT, 94 % for CZP, 90 % for ABA and 87 % for TCZ (Table 1, Figure 1). <b>In the primary analysis</b> (adjusted logistic regression), ultrasound remission rates were higher with borderline statistical significance for CZP vs ACT, OR (95%CI) 5.46 (1.33, 22.52) p=0.05and ABA vs ACT OR 4.51 (1.27, 16.00) p=0.06 and not significant for TCZ vs ACT, OR 2,26 (0.71, 7.19) p=0.40. More patients achieved ultrasound remission compared to clinical remission in all treatment arms at 48 weeks. Patients in ultrasound remission, but not in clinical remission (n=56) had higher tender joint counts (8.5 vs 0.6), patient's global (28.1 vs 4.8) and physician's global (10.8 vs 1.3) scores than patients who were in both ultrasound and clinical remission. Swollen joint count (1.0 vs 0.1), ESR (9.3 vs 10.7) and CRP (2.6 vs 2.5) were similar in both groups. <h3>Conclusion:</h3> A large proportion of patients with early RA achieved ultrasound remission in the NORD-STAR trial. Higher remission rates were achieved in the biologic treatment arms compared to active conventional treatment which is in line with the clinical results. Substantially more patients achieved ultrasound remission than CDAI remission. <h3>REFERENCES:</h3> [1] Hetland et al. BMJ 2020;371:m4328. [2] Østergaard M et al. Ann Rheum Dis. 2023;82(10):1286-1295. <b>Table 1.</b> Demographics/baseline (BL) characteristics and 48 weeks results. Values are mean (SD), if not otherwise indicated. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Marte S Heiberg: None declared, Yogan Kisten: None declared, Amirhossein Kazemi: None declared, Hamed Rezaei: None declared, Erik af Klint: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, David Stevens: None declared, Gunnstein Bakland UCB, Lars Fridtjof Karoliussen: None declared, Pernille Bolton-King: None declared, Joakim Lindqvist: None declared, Kristina Lend: None declared, Jon Lampa: None declared, Till Uhlig: None declared, Merete Lund Hetland MLH received research grants from AbbVie, Biogen, BMS, Celtrion, Eli Lily, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis; and institution pay from Pfizer, Medac, AbbVie and Sandoz; chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; cochairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis., Anna Rudin: None declared, Dan Nordström DCN received consulting fees from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB' meeting support from Pfizer; advisory board participation fee from Novartis; and other service fee by BMS., Bjorn Gudbjornsson: None declared, Michael T Nurmohamed MTN received research grants from AbbVie, BMS, Pfizer, Galapagos, Amgen and Eli Lily. BG received consulting fee from Novartis and honorary lecture payment from Novartis and Nordic-Pharma., Mikkel Østergaard MØ received the study drug from BMS and UCB; research grants from Abbvie, BMS, Merck, Novartis and UCB; speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB; and consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB., Gerdur Grondal: None declared, Tuulikki Sokka-Isler: None declared, Hilde Berner Hammer: None declared, Ronald F. van Vollenhoven RFvV received the study drug from BMS and UCB; research grants from BMS, GSK, UCB and AstraZeneca; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB; expert fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB; and advisory board fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB., Espen Haavardsholm: None declared.