Clinical and Laboratory Characteristics of Persistently Antiphospholipid Antibody Positive Patients: Retrospective Results from Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

Ecem Sevim¹, Diane F. Zisa², Danieli Andrade³, Vittorio Pengo⁴, Maria Tektonidou⁵, Amaia Ugarte⁶, Maria Gerosa⁷, Lanlan Ji⁸, Maria Efthymiou⁹, Guilherme Ramires de Jesus¹⁰, David Branch¹¹, Cecilia Nalli¹², Savino Sciascia¹³, H. Michael Belmont¹⁴, Paul R. Fortin¹⁵, Michelle Petri¹⁶, Esther Rodriguez-Almaraz¹⁷, Rosana Quintana¹⁸, Jason S Knight¹⁹, Rohan Willis²⁰, Tatsuya Atsumi²¹, Maria Laura Bertolaccini²², Doruk Erkan²³ and Medha Barbhaiya²⁴, ¹Rheumatology, Hospital for Special Surgery, New York, NY, ²Department 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, ⁴Azienda Ospedaliera of Padova, 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, ⁸Rheumatology and Immunology, Peking University First Hospital, Beijing, China., Beijing, China, ⁹Haemostasis Research Unit, Department of Haematology, University College London, London, United Kingdom, ¹⁰Obstetrics, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, ¹¹Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT, ¹²Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy, ¹³Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Torino, Italy, ¹⁴Medicine, NYU Langone Health, New York, NY, ¹⁵Medicine, CHU de Québec - University of Laval, Quebec, QC, Canada, ¹⁶Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁷Hospital Universitario 12 de Octubre, Madrid, Spain, ¹⁸Argentina, GLADEL, Rosario, Argentina, ¹⁹University of Michigan, Ann Arbor, MI, ²⁰301 University Blvd, Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, TX, USA, Galveston, TX, ²¹Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, ²²King's College London, London, United Kingdom, ²³Rheumatology, Hospital for Special Surgery- Weill Cornell Medicine, New York, NY, ²⁴Rheumatology, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: antiphospholipid antibodies and antiphospholipid syndrome

Session Information

Date: Sunday, October 21, 2018

Title: Antiphospholipid Syndrome Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: APS ACTION Registry was created to study long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients with/without other systemic autoimmune diseases (SAIDx). The primary objective of this analysis was to report the baseline demographic, clinical, and laboratory characteristics of aPL-positive patients enrolled since 2012. Secondly, we analyzed the association between aPL-profiles and aPL-related events at baseline.

Methods: A web-based data capture system is used to store patient demographics and aPL-related medical history. Inclusion criteria are positive aPL, based on the Updated Sapporo APS Classification Criteria, tested at least twice within one year prior to enrollment (IgA aCL/aβ₂GPI included whenever available). Patients are followed every 12±3 months with clinical data and blood collection. For this analysis, aCL and aβ₂GPI IgG/M/A positivity was defined as a titer of ≥40 U, based on local enrollment tests, and criteria and non-criteria (NC) aPL manifestations were retrieved (Table). To test the association between aPL profiles and clinical outcomes, we used chi-square test or Fisher’s exact test for categorical variables.

Results: As of 12/2017, 714 patients were enrolled from 26 centers worldwide (mean age at entry: 45 ± 13y; female: 530 [74%]; white: 460 [64%]; and other SAIDx: 257 [36%]). Historically, 161 (23%) had aPL-positivity without APS; 393 (55%) thrombotic APS (TAPS); 66 (9%) obstetric APS (OAPS); and 94 (13%) TAPS+OAPS. 48% and 63% of TAPS patients had arterial and venous thrombosis, respectively (14% both); 1% had catastrophic APS. 81 of 161 (50%) and 263 of 553 (48%) of patients without and with clinical APS classification, respectively, had ≥1 NC aPL manifestation. Livedo (p=0.002) and skin ulcers (p=0.047) were more frequent in patients with TAPS+OAPS and TAPS (with/without OAPS), respectively (vs aPL-positive patients without APS). Based on inclusion aPL, 585 (82%) patients were tested for all three aPL; 222/585 (38%) were triple aPL-positive. Thrombosis, pregnancy morbidity, and NC aPL manifestation rates were similar across different aPL profiles except (Table): a) ≥3 consecutive (pre)embryonic losses and cardiac valve disease differed when compared between triple-, double-, and single aPL-positive patients; and b) livedo was higher in isolated LA-positive patients compared to triple aPL-positive patients.

Conclusion: In our international aPL-positive cohort, at baseline: a) one-fourth of patients do not fullfill clinical APS classification critera; b) almost half have at least one non-criteria aPL manifestation; c) livedo and skin ulcers are more common in thrombotic APS patients; and d) there is no association between the aPL-related criteria events and aPL profile. Future prospective registry analysis, accounting for potential confounders and using standardized core laboratory aPL test results, will help clarify aPL risk profiles.

Baseline Clinical Characteristics of 714 Patients Included in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”) Between 2012-2018, by Antiphospholipid Antibody (aPL) Profile

Baseline Clinical Characteristics

P¹

LA only

Positivity

(134)

Triple* aPL

Positivity

(222)

Double* aPL

Positivity

(176)

Single* aPL

Positivity

(179)

P²

Any Vascular thrombosis

– Arterial Thrombosis

– Venous Thrombosis

– Small Vessel Thrombosis

Transient Ischemic Attacks

Catastrophic APS

0.29

0.51

0.93

0.47

0.53

0.52

100 (75%)

40 (30%)

70 (52%)

6 (4%)

9 (7%)

1 (1%)

154 (69%)

68 (31%)

107 (48%)

13 (6%)

19 (9%)

2 (1%)

114 (65%)

60 (34%)

66 (38%)

10 6%)

17 (10%)

2 (1%)

122 (68%)

51 (29%)

82 (46%)

7 (4%)

12 (7%)

0.61

0.24

0.10

0.62

0.60

0.38

Any Pregnancy Morbidity

– ≥ 1 Fetal Death ≥ 10^th w

– ≥ 1 Preterm Delivery <34^thw

– ≥ 1 Pre-Emb/Emb Loss < 10^th w

– ≥ 3 Pre-Emb/Emb Loss < 10^th w

0.22

0.33

0.21

0.22

0.17

51 (38%)

26 (37%)

11 (16%)

31 (44%)

9 (13%)

58 (26%)

35 (60%)

19 (33%)

28 (48%)

5 (9%)

60 (34%)

31 (52%)

18 (30%)

31 (52%)

3 (5%)

64 (36%)

34 (53%)

12 (19%)

38 (59%)

11 (17%)

0.64

0.60

0.20

0.50

0.041

Any Non-Criteria Manifestation

– Livedo Reticularis/Racemosa

– Persistent Thrombocytopenia

– Persistent Hemolytic Anemia

– Cardiac Valve Disease

– Skin Ulcers

– aPL-associated Nephropathy**

0.78

0.032

0.05

0.70

0.06

0.77

0.50

70 (52%)

23 (17%)

8 (6%)

8/112 (7%)

5 (4%)

2 (2%)

116 (52%)

21 (9%)

54 (24%)

14 (6%)

26/181 (14%)

7 (3%)

96 (55%)

24 (14%)

31 (18%)

5 (3%)

14/149 (9%)

7 (4%)

4 (2%)

87 (49%)

24 (13%)

27 (15%)

9 (5%)

9/152 (6%)

7 (4%)

2 (1%)

0.40

0.34

0.051

0.28

0.037

0.89

0.41

*Triple (LA+aCL+aβ₂GPI), double (two tests based on LA, aCL, or aβ₂GPI), and single (LA, aCL, or aβ₂GPI); ** Biopsy-proven.

p¹: comparison between triple aPL and LA only positivity; p²: comparison between triple, double, and single aPL positivity.

Note: Among 585 patients, only one patient included in the registry because of isolated IgA positivity; and b) only three patients switched groups because of IgA (groups were determined based on the highest isotype titer).

Disclosure: E. Sevim, None; D. F. Zisa, None; D. Andrade, None; V. Pengo, None; M. Tektonidou, None; A. Ugarte, None; M. Gerosa, None; L. Ji, None; M. Efthymiou, None; G. Ramires de Jesus, None; D. Branch, None; C. Nalli, None; S. Sciascia, None; H. M. Belmont, None; P. R. Fortin, None; M. Petri, None; E. Rodriguez-Almaraz, None; R. Quintana, None; J. S. Knight, None; R. Willis, None; T. Atsumi, None; M. L. Bertolaccini, None; D. Erkan, None; M. Barbhaiya, RRF, 2.

To cite this abstract in AMA style:

Sevim E, Zisa DF, Andrade D, Pengo V, Tektonidou M, Ugarte A, Gerosa M, Ji L, Efthymiou M, Ramires de Jesus G, Branch D, Nalli C, Sciascia S, Belmont HM, Fortin PR, Petri M, Rodriguez-Almaraz E, Quintana R, Knight JS, Willis R, Atsumi T, Bertolaccini ML, Erkan D, Barbhaiya M. Clinical and Laboratory Characteristics of Persistently Antiphospholipid Antibody Positive Patients: Retrospective 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/clinical-and-laboratory-characteristics-of-persistently-antiphospholipid-antibody-positive-patients-retrospective-results-from-antiphospholipid-syndrome-alliance-for-clinical-trials-and-international/. Accessed .

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