First and Recurrent Thrombosis Risk after 1897 Patient-Years of Follow-up: Prospective Results from Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

Ecem Sevim¹, Ozan Unlu², Danieli Andrade³, Alessandra Banzato⁴, Maria Tektonidou⁵, Amaia Ugarte⁶, Maria Gerosa⁷, Hannah Cohen⁸, David Branch⁹, Guilherme Ramires de Jesus¹⁰, Angela Tincani¹¹, Paul R. Fortin¹², Michelle Petri¹³, Ignasi Rodriguez¹⁴, Jason S Knight¹⁵, Tatsuya Atsumi¹⁶, Rohan Willis¹⁷, Robert Roubey¹⁸ and Doruk Erkan¹⁹, ¹Rheumatology, Hospital for Special Surgery, New York, NY, ²Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, USA., New York, NY, ³Rheumatology, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil, ⁴Department of Cardiac Thoracic and Vascular Sciences, Clinical Cardiology, Thrombosis Centre, University of Padova, Padova, Italy, ⁵Rheumatology Unit, 1st Dept. of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Athens University Medical School, Athens, Greece, ⁶Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Biscay, Spain, ⁷Istituto Ortopedico Gaetano Pini, University of Milan, Milano, Italy, ⁸Haemostasis Research Unit, Department of Haematology, University College London, London, United Kingdom, ⁹Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT, ¹⁰Obstetrics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, ¹¹University and Spedali Civili of Brescia, Brescia, Italy, ¹²Medicine, CHU de Québec - University of Laval, Quebec, QC, Canada, ¹³Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁴Rheumatology, Hospital Clinica, Barcelona, Spain, ¹⁵University of Michigan, Ann Arbor, MI, ¹⁶Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, ¹⁷301 University Blvd, Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, TX, USA, Galveston, TX, ¹⁸Rheumatology, Allergy, and Immunology, Department of Medicine and Thurston Arthritis Research Center, Division of Rheumatology, Allergy and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, ¹⁹Rheumatology, Hospital for Special Surgery- Weill Cornell Medicine, New York, NY

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Anticoagulation, antiphospholipid antibodies and thrombosis

Session Information

Date: Sunday, October 21, 2018

Title: 3S079 ACR Abstract: Antiphospholipid Syndrome (851–856)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: APS ACTION Registry was created to study the natural course of disease over 10 years in persistently antiphospholipid antibody (aPL)-positive patients with/without other systemic autoimmune diseases (SAIDx). Previously, we reported the annual recurrent and first thrombosis risk in persistently aPL-positive patients as 2.63% and 1.68%, respectively (Arthritis Rheumatol 2017;69:sup10).

Methods: A web-based data capture system is used to store patient demographics and aPL-related history. The inclusion criteria are positive aPL based on the laboratory section of the Updated Sapporo APS Classification Criteria, tested ≥2 within 1 year prior to enrollment. Patients are followed every 12±3 months and receive advice on cardiovascular disease and thrombosis prevention at each visit. Based on patients who completed 1, 2, 3, 4, and 5 year follow-up visits, we report the incident thrombosis risk in persistently aPL-positive patients with/without a history of thrombosis. We also compare the characteristics of patients with/without new thrombosis.

Results: As of 5/2018, 735 patients were included: aPL/APS without SAIDx: 472 (no APS: 87; thrombotic APS [TAPS]: 272; obstetric APS [OAPS]: 51; and TAPS+OAPS: 62]; and aPL/APS with SAIDx: 263 [no APS: 72; TAPS: 136; OAPS: 19; and TAPS+OAPS: 36]). Of 735 patients, 572, 473, 396, 264, and 71 completed 1, 2, 3, 4, and 5 year follow-up visits, respectively. Mean follow up was 2.6 years (1308 patient-years [pt-y]) and 2.54 years (589 pt-y) for those with and without a history of thrombosis, respectively. Based on 45 recurrent events in 36 patients, and 9 initial events since the inception of the registry (Table), the incident thrombosis risk was 2.75 and 1.53 per 100 pt-y in patients with and without history of thrombosis, respectively. Demographics, concomitant lupus diagnosis, aPL-profile, medications, and non-aPL thrombosis risk factors were not different between APS patients with (n: 36) or without (n: 376) recurrent thrombosis, and between aPL-positive patients with (n: 9) or without (n: 184) initial thrombosis except: APS patients with recurrence (vs those without recurrence), were younger (40.6+13.2 vs 45.71, p 0.04) and more likely to receive direct oral anticoagulants (3/36 [8%] vs 9/376 [2%], p 0.04) or no antiplatelet/anticoagulants (6/36 [17%] vs 15/376 [4%], p 0.001).

Conclusion: Based on approximately 2000 patient years of follow-up, the incident thrombosis risk in persistently aPL-positive patients remains relatively low (2.75 and 1.53 per 100 pt-y in patients with and without history of thrombosis, respectively) and commonly associated with LA- and/or triple aPL-positivity as well as non-aPL thrombosis risk factors and sub-therapeutic international normalized ratios. Future cox proportional analysis of APS ACTION registry will better determine the risk of thrombosis in persistently aPL-positive patients based on different risk profiles.

Table: Clinical and Laboratory Characteristics of Patients with Recurrent and Initial Events Since the Inception of AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”)

N (%)

# of APS Patients with Recurrent Events

n: 36

# of aPL-positive Patients with Initial Events

n: 9

Mean age (registry entry) (± SD)

40.58 ± 13.20

38± 14.47

Female

27 (75%)

8 (89%)

Other Autoimmune Diseases

9 (25%)

3 (33%)

aPL Profile

· Triple aPL-positive

· Double aPL-positive

· Single aPL positive (aCL or aβ₂GPI)

· Single aPL positive (LA)

· LA-positive with/without aCL/aβ₂GPI

17 (47%)

10 (28%)

1 (3%)

8 (22%)

31 (86%)

2 (22%)

3 (33%)

2 (22%)

6 (67%)

N (%)

# of Recurrent Events

n: 45*

# of Initial Events

n: 9

New Events

· Venous Thrombosis

· Arterial Thrombosis

· Microthrombosis

23 (51%)

19 (42%)

3 (7%)

5 (56%)

3 (33%)

1 (11%)

Antiplatelet & Anticoagulant Treatment

· VKA Only

· LMWH Only

· VKA + Antiplatelet Agent

· LMWH + Antiplatelet Agent

· Antiplatelet Agent only

· None

21 (47%)

6 (13%)

5 (14%)

3 (9%)

2 (4%)

5 (11%)

–

4 (44%)

5 (56%)

Other Treatments

· Hydroxychloroquine

· Statin

· Direct Oral Anticoagulants

17 (38%)

13 (29%)

3 (9%)

3 (33%)

1 (11%)

–

Non-aPL Risk Factors at the Time of Events

· Sub-therapeutic INR (<2)**

· CVD Risk Factors***

· Immobilization/surgery

· Homozygous MTHFR Polymorphism

· Estrogen-containing OCP Use

19/26 (73%)

33 (73%)

8 (18%)

1/15 (7%)

1 (7%)

–

4 (44%)

3 (33%)

–

LA: lupus anticoagulant; aCL: anticardiolipin antibody; aβ₂GPI: anti-β2-glycoprotein-I antibody; VKA: vitamin K antagonists; LMWH: low-molecular weight heparin; INR: international normalized ratio; CVD: cardiovascular disease; OCP: oral contraceptive pill. *: 2 events in 2 patients, 3 in 2 patients, and 4 in 1 patient; **: unknown in one patient, mean INR in 19 patients = 1.58; ***: CVD Risk Factors: Hypertension, Hyperlipidemia, Diabetes Mellitus, Obesity, Current Smoking, Family History of Early CVD, and Renal Failure

Disclosure: E. Sevim, None; O. Unlu, None; D. Andrade, None; A. Banzato, None; M. Tektonidou, None; A. Ugarte, None; M. Gerosa, None; H. Cohen, None; D. Branch, None; G. Ramires de Jesus, None; A. Tincani, Bristol-Myers Squibb, 2,UCB, Inc., 5; P. R. Fortin, None; M. Petri, None; I. Rodriguez, None; J. S. Knight, None; T. Atsumi, None; R. Willis, None; R. Roubey, None; D. Erkan, None.

To cite this abstract in AMA style:

Sevim E, Unlu O, Andrade D, Banzato A, Tektonidou M, Ugarte A, Gerosa M, Cohen H, Branch D, Ramires de Jesus G, Tincani A, Fortin PR, Petri M, Rodriguez I, Knight JS, Atsumi T, Willis R, Roubey R, Erkan D. First and Recurrent Thrombosis Risk after 1897 Patient-Years of Follow-up: Prospective Results from Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository (“Registry”) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/first-and-recurrent-thrombosis-risk-after-1897-patient-years-of-follow-up-prospective-results-from-antiphospholipid-syndrome-alliance-for-clinical-trials-and-international-networking-aps-action-cli/. Accessed .

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