AB0684 EFFECTIVENESS AND SAFETY OF MONO-OR COMBINATION THERAPY WITH SARILUMAB IN RHEUMATOID ARTHRITIS: 24-MONTH, SINGLE-ARM, GERMAN PROSARA STUDY
Authors: E. Feist, P. M. Aries, S. Zinke, K. Krüger, C. Barrionuevo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Biological disease-modifying antirheumatic drugs (bDMARDs) are effective in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic DMARD (csDMARD) therapy<sup>1</sup>. Sarilumab, an interleukin 6 receptor inhibitor (IL-6Ri), has demonstrated treatment effectiveness in RA in routine care in the USA<sup>2</sup> and elsewhere<sup>3</sup>, but few data are available for long-term use in such a setting. <h3>Objectives:</h3> This study aimed to assess the effectiveness, safety and, patient-reported outcomes of sarilumab in daily clinical practice in patients with RA over a prolonged observation period. <h3>Methods:</h3> This prospective, non-interventional, multi-center, open label, single-arm study (PROSARA) was conducted from March 2018 to February 2023 at 78 sites in Germany. Adult patients with moderate to severe RA, with prior RA therapy and treated for the first time with sarilumab (mono or combination therapy) (150 mg/ 200 mg Q2W) were enrolled. Clinical effectiveness of sarilumab was assessed at 12 and 24 months using clinical disease activity index (CDAI), simplified disease activity index (SDAI), disease activity score in 28 joints (DAS28) based on both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (DAS28<sub>CRP/ESR</sub>), and health assessment questionnaire disability index (HAQ-DI) score. Influence of prior RA treatment on effectiveness was determined using logistic regression. Safety was assessed by frequency of adverse event (AE), serious AE (SAE), adverse drug reaction (ADR), AE/SAE leading to study drug withdrawal. All analyses for patients (baseline, effectiveness, and safety population) initiating sarilumab close to baseline (BL) (±14 days) were presented to ensure a meaningful interpretation due to potential deviation in the start of sarilumab from the date of BL visit. <h3>Results:</h3> A total of 584 patients (76.9% female, mean±SD age: 58.6 ± 11.5 years, median time since diagnosis: 91 months [~7.6 years; IQR: 39–187]) were included in the BL and safety population, of whom 541 patients had at least 1 BL and 1 corresponding post-BL effectiveness assessment documented. The safety analysis population included patients who were administered ≥1 dose of study medication. At BL, 54.5% of patients started sarilumab as monotherapy, while 30.7% received sarilumab in combination with csDMARD, (mainly methotrexate, 89.9%), data for the remaining patients unknown. Disease activity showed a clinically relevant improvement in all assessed parameters (Table 1). At 24 months, the majority of patients were in DAS28 remission (DAS28<sub>CRP</sub>; 61.4% and DAS28<sub>ESR</sub>; 72.4%), whereas 28.4% and 28.0% of patients were in CDAI and SDAI remission, respectively. DAS28 remission was not significantly associated with prior RA treatment (except for DAS28<sub>CRP</sub> remission for TNFi). Mean improvement of 0.3 points was observed in the HAQ-DI score after 12 and 24 months of therapy onset (Table 1). About 47.6% of the patients discontinued the study prematurely due to lack (27.5%) or loss (20.5%) of effectiveness or intolerance (24.9%). SAEs (175) were reported in 104 patients of the safety population (Table 2). Most frequent SAEs were musculoskeletal and connective tissue disorders (3.9%), surgical and medical procedures (2.6%), and infections and infestations (2.4%). Most frequent serious ADRs were musculoskeletal and connective tissue (1.4%) and blood and lymphatic system disorders (0.7%). There was one death, not related to study drug. <h3>Conclusion:</h3> In daily clinical practice in Germany, sarilumab showed sustained improvement in various effectiveness parameters in RA and sarilumab was well tolerated with no new safety signals. These data are consistent with results of similar clinical trials with sarilumab in patients with RA. <h3>REFERENCES:</h3> [1] Bonek K, et al. <i>Cells</i>. 2021;10(2):323 [2] Curtis JR, et al. <i>Rheumatol Ther</i>. 2023;10(4):1055–1072 [3] Kameda H, et al. <i>Mod Rheumatol</i>. 2023 <h3>Acknowledgements:</h3> The non-interventional study PROSARA was funded by Sanofi Deutschland GmbH and Regeneron Pharmaceuticals, Inc. Medical writing support for this abstract was provided by Sambuddha Das, PhD., of Sanofi. <h3>Disclosure of Interests:</h3> Eugen Feist Reports grants and personal fees from Sanofi during the conduct of the study; grants and personal fees from Roche, Abbvie, BMS, Lilly outside the submitted work, Peer Malte Aries Reports personal fees from Abbvie, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB, Janssen, Medac, Sanofi, Silke Zinke Reports personal fees from Abbvie, GSK, UCB, Lilly, Janssen, Sanofi, Klaus Krüger Reports personal fees from Sanofi, Christian Barrionuevo Is employee of Sanofi Deutschland GmbH.