1604: First and Recurrent Thrombosis Risk After 4,454 Patient-Years of Follow-Up: Prospective Results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”)
Hospital for Special Surgery New York, NY, United States
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Jonathan Thaler1, Yasaman Ahmadzadeh2, Danieli Andrade3, leslie skeith4, Maria Tektonidou5, Savino Sciascia6, Vittorio Pengo7, Jose Pardos-Gea8, Guillermo Ruiz-Irastorza9, Chary Lopez-Pedrera10, H Michael Belmont11, Kello Nina12, Paul R. Fortin13, Denis WAHL14, Maria Gerosa15, Guilherme De Jesús16, Zhuoli Zhang17, Tatsuya Atsuma18, Maria Efthymiou19, D. Ware Branch20, Laura Andreoli21, Esther Rodriguez almaraz22, Michelle Petri23, Giulia Pazzola24, Ricard Cervera25, Bahar Artim Esen26, Hui Shi27, Jason Knight27, Guillermo Pons-Estel28, Rohan Willis29, Ali Duarte-Garcia30, Maria Laura Bertolaccini31, Hannah Cohen32, Doruk Erkan1 and On Behalf Of APS ACTION33, 1Hospital for Special Surgery, New York, NY, 2Roger Williams Medical Center, Providence, RI, 3University of São Paulo, São Paulo, Brazil, 4University of Calgary, Calgary, AB, Canada, 5Joint Academic Rheumatology Program, First Department of Propedeutic and Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 6University of Turin, Torino, Italy, 7Department of Cardiac-Thoracic-Vascular Sciences and Public Health University of Padova, Padova, Italy, 8Vall d'Hebron University Hospital, Barcelona, Spain, 9Hospital Universitario Cruces, Barakaldo, Spain, 10IMIBIC - Reina Sofia Hospital, Córdoba, Spain, 11NYU School of Medicine, New York, NY, 12Northwell Health, Brooklyn, NY, 13Centre ARThrite - CHU de Québec - Université Laval, Quebec City, QC, Canada, 14University of Lorraine, Nancy, France, 15University of Milan, Milano, Italy, 16Universidade do Estado do Rio de Janeiro, Rio De Janeiro, Brazil, 17Peking University First Hospital, Rheumatology and Immunology Department, Beijing, China, 18Hokkaido University, Department of Rheumatology, Endocrinology and Nephrology, Sapporo, Japan, 19University College London, London, United Kingdom, 20University of Utah, Salt Lake City, UT, 21University of Brescia, Brescia, Italy, 22Hospital Universitario 12 de Octubre, Madrid, Spain, 23Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Timonium, MD, 24Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia, Reggio Emilia, Italy, 25Hospital Clínic de Barcelona, Barcelona, Spain, 26Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 27University of Michigan, Ann Arbor, MI, 28CREAR, Rosario, Argentina, 29University of Texas Medical Branch, Galveston, TX, 30Mayo Clinic, Rochester, MN, 31King's College London, London, United Kingdom, 32University College London Hospitals NHS Foundation Trust, London, United Kingdom, 33on behalf of APS ACTION, New York, NY
Background/Purpose: The APS ACTION Registry was created to study the natural course of disease over 10 years in persistently antiphospholipid antibody (aPL)-positive patients with or without other systemic autoimmune diseases (SAID). The primary objective of this study was to update the incident first and recurrent thrombosis risk in registry-enrolled patients, previously reported in 2021 as 1.02 and 2.09 per 100 pt-y, respectively (Arthritis Rheumatol.2021;73[suppl 9]).
Methods: A web-based data capturing system is used to store patient demographics, history, and medications. The inclusion criteria are positive aPL according to the Updated Sapporo Classification Criteria, tested within one year prior to enrollment. Follow-up occurs every 12±3m with clinical data and blood collection. In this prospective analysis, based on patients who completed 1- to 10-year follow-up visits, we report the incident thrombosis risk in persistently aPL-positive patients with and without a history of thrombosis. Secondarily, we compare baseline clinical and laboratory characteristics of patients with vs without new thrombosis.
Results: As of April 2023, 1,166 patients were enrolled; 22 patients with a prior history of transient ischemic attack and no prior imaging-confirmed thrombosis were excluded. Five other patients were excluded due to incomplete data. Of the remaining 1,139 patients; a) 606 had aPL/APS without SAID, including aPL without APS classification (n=125), thrombotic APS (TAPS, n=357), obstetric APS (OAPS, n=57), and TAPS+OAPS (n=67); and b) 533 patients had aPL/APS associated with SAID, including aPL without APS (n=164), TAPS (n=269), OAPS (n=35), and TAPS+OAPS (n=65). Mean follow-up (enrollment to first new thrombosis or most recent follow-up) was 3.67 years (1401 pt-y) and 4.03 years (3053 pt-y) for those without and with a history of thrombosis, respectively. Based on 14 first events in 14 patients, and 88 recurrent events in 65 patients (Table 1), the incident thrombosis risk was 1.00 and 2.13 per 100 pt-y in patients without and with a history of thrombosis, respectively. Baseline characteristics were similar between aPL-positive patients with (n=14) or without (n=368) first thrombosis, and between APS patients with (n=65) or without (n=692) recurrent thrombosis, except: a) obesity, renal failure, and direct oral anticoagulant use were more common in APS patients with recurrent thrombosis than in those without (p=0.02, 0.01, and 0.005, respectively); and b) smoking history was more common in patients with first thrombosis than in those without (p=0.05) (Table 2). Table 3 describes patient characteristics at the time of new events.
Conclusion: Based on 4,454 pt-y of follow-up, the incident thrombosis risk in persistently aPL-positive patients remains relatively low. Secondary analysis revealed possible differences in medications and cardiovascular risk factors at enrollment between patients with and without thrombosis during follow-up, but these results should be interpreted with caution given the large number of covariates analyzed (multiplicity). Future Cox proportional hazards analysis will help better define the risk and protective factors for thrombosis in persistently aPL-positive patients.
Table 1: Frequencies and Types of New Thrombotic Events Since the Inception of APS ACTION Registry
Table 2: Baseline Clinical and Laboratory Characteristics of Patients With vs Without Thrombosis Since the Inception of APS ACTION Registry
Table 3: Clinical and Laboratory Characteristics of Patients (at the time of events) with First and Recurrent Thrombotic Events Since the Inception of APS ACTION Registry
J. Thaler: None; Y. Ahmadzadeh: None; D. Andrade: None; l. skeith: CSL Behring, 5, Leo Pharma, 6; M. Tektonidou: None; S. Sciascia: None; V. Pengo: Werfen group, Milan, Italy, 6; J. Pardos-Gea: Roche, 6; G. Ruiz-Irastorza: None; C. Lopez-Pedrera: None; H. Belmont: Alexion, 6, Aurinia, 6; K. Nina: None; P. Fortin: AbbVie, 1, AstraZeneca, 1, 6, GlaxoSmithKlein(GSK), 1, 6, Roche-Genentech, 1; D. WAHL: None; M. Gerosa: None; G. De Jesús: GlaxoSmithKlein(GSK), 5, UCB, 1; Z. Zhang: None; T. Atsuma: AbbVie, 5, 6, Alexion, 5, 6, Astellas, 5, 6, Boehringer-Ingelheim, 2, Bristol-Myers Squibb, 6, Chugai, 5, 6, Daiichi Sankyo, 5, 6, Eisai, 5, 6, Eli Lilly, 5, 6, Gilead, 5, 6, GSK, 2, 5, Merck Sharp & Dohme, 2, 6, Mitsubishi Tanabe Pharma, 5, 6, Otsuka, 5, 6, Pfizer, 5, 6, Sanofi/Genzyme, 2, 6, Takeda, 5, 6, UCB, 5, 6; M. Efthymiou: Alexion, 1, Immune Tolerance Network (ITN), 1; D. Branch: UCB Pharmaceuticals, 5; L. Andreoli: None; E. Rodriguez almaraz: None; M. Petri: Alexion, 1, Amgen, 1, AnaptysBio, 1, Annexon Bio, 1, Argenx, 1, Arhros-Focus Med/Ed, 6, AstraZeneca, 1, 5, Aurinia, 1, 5, 6, Axdev, 1, Biogen, 1, Boxer Capital, 2, Cabaletto Bio, 2, Caribou Biosciences, 2, CVS Health, 1, Eli Lilly, 1, 5, Emergent Biosolutions, 1, Exagen, 5, Exo Therapeutics, 2, Gilead Biosciences, 2, GlaxoSmithKlein(GSK), 1, 5, 6, Horizon Therapeutics, 2, Idorsia Pharmaceuticals, 2, IQVIA, 1, Janssen, 1, 5, Kira Pharmaceuticals, 2, MedShr, 6, Merck/EMD Serono, 1, Momenta Pharmaceuticals, 2, Nexstone Immunology, 2, Nimbus Lakshmi, 2, Proviant, 2, Sanofi, 2, Sinomab Biosciences, 2, Thermofisher, 5, UCB, 2; G. Pazzola: None; R. Cervera: None; B. Artim Esen: None; H. Shi: None; J. Knight: Jazz Pharmaceuticals, 2; G. Pons-Estel: GlaxoSmithKlein(GSK), 1, 5, 6, Janssen, 1, 5, 6, Novartis, 1, 6, Pfizer, 5, 6, Werfen/Inova, 5, 6; R. Willis: None; A. Duarte-Garcia: None; M. Bertolaccini: None; H. Cohen: argenx, 1, Roche, 1, Technoclone (paid to University College London Hospital (UCLH) Charity), 6, UCB Biopharma (paid to UCLH Charity), 2; D. Erkan: Abbvie, 1, ACR/EULAR, 5, APS ACTION, 12, Executive Committee Co-chair, Argenx, 1, Aurinia, 6, Chugai, 1, Exagen, 5, GSK, 5, 6, NIH-NIAID, 5, Up-To-Date, 9; O. Of APS ACTION: None.