Validation of New Systemic Lupus Erythematosus Classification Criteria

Martin Aringer¹, Karen Costenbader², Ralph Brinks³, Dimitrios Boumpas⁴, David Daikh⁵, David Jayne⁶, Diane L. Kamen⁷, Marta Mosca⁸, Rosalind Ramsey-Goldman⁹, Josef S. Smolen¹⁰, David Wofsy¹¹, Betty Diamond¹², Søren Jacobsen¹³, W. Joseph McCune¹⁴, Guillermo Ruiz-Irastorza¹⁵, Matthias Schneider¹⁶, Murray Urowitz¹⁷, George Bertsias¹⁸, Bimba Hoyer¹⁹, Nicolai Leuchten¹, Chiara Tani²⁰, Sara K. Tedeschi²¹, Zahi Touma²², Branimir Anic²³, Florence Assan²⁴, Tak Mao Chan²⁵, Ann E. Clarke²⁶, Peggy Crow²⁷, László Czirják²⁸, Andrea Doria²⁹, Winfried Graninger³⁰, Bernadett Halda-Kiss²⁸, Sarfaraz A. Hasni³¹, Peter M. Izmirly³², Michelle Jung³³, Gabor Kumanovics²⁸, Xavier Mariette²⁴, Ivan Padjen²³, JM Pego-Reigosa³⁴, Juanita Romero-Díaz³⁵, Iñigo Rúa-Figueroa³⁶, Raphaele Seror³⁷, Georg Stummvoll³⁸, Yoshiya Tanaka³⁹, Maria Tektonidou⁴⁰, Carlos Vasconcelos⁴¹, Edward M Vital⁴², Daniel J. Wallace⁴³, Sule Yavuz⁴⁴, Raymond P. Naden⁴⁵, Thomas Dörner⁴⁶ and Sindhu Johnson⁴⁷, ¹Medicine III, University Medical Center and Faculty of Medicine TU Dresden, Dresden, Germany, ²Rheumatology, Immunology and All, Brigham & Women's Hospital, Boston, MA, ³Department of Rheumatology & Hiller Research Unit, Heinrich-Heine University, Düsseldorf, Germany, ⁴University of Athens, Athens, Greece, ⁵Rheumatology, UCSF and VA Medical Center, San Francisco, CA, ⁶Department of Medicine, University of Cambridge, Cambridge, United Kingdom, ⁷Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, ⁸Rheumatology Unit, University of Pisa, Pisa, Italy, ⁹FSM, Northwestern University, Chicago, IL, ¹⁰Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria, ¹¹University of California San Francisco, San Francisco, CA, ¹²Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research, Manhasset, NY, ¹³University of Copenhagen, Copenhagen, Denmark, ¹⁴Int Med/ Rheum, University of Michigan, Ann Arbor, MI, ¹⁵Autoimmune Diseases Research Unit, BioCruces, Hospital Universitario Cruces, Baracaldo, Spain, ¹⁶Department and Hiller Research Center for Rheumatology, Heinrich-Heine University, Duesseldorf, Germany, ¹⁷University of Toronto Lupus Research Program, Toronto Western Hospital, Toronto, ON, Canada, ¹⁸Department of Rheumatology, Clinical Immunology and Allergy, University of Crete, School of Medicine, Heraklion, Greece, ¹⁹University of Schleswig-Holstein, Kiel, Germany, ²⁰University of Pisa, Pisa, Italy, ²¹Rheumatology Immunology & Allergy, Brigham & Women's Hospital, Boston, MA, ²²University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ²³Department of Internal Medicine, University Hospital Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia, ²⁴Université Paris Sud, Paris, France, ²⁵University of Hong Kong, Hong Kong, Hong Kong, ²⁶Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ²⁷Department of Medicine, Hospital for Special Surgery, New York, NY, ²⁸Rheumatology and Immunology, University of Pécs, Pécs, Hungary, ²⁹University and Azienda Ospedaliera of Padova, Padova, Italy, ³⁰Rheumatology and Immunology, Medical University of Graz, Graz, Austria, ³¹Lupus Clinical Research Program, Office of the Clinical Director, NIH/NIAMS, Bethesda, MD, ³²NYU Langone Health, New York, NY, ³³University of Calgary, Calgary, AB, Canada, ³⁴Complexo Hospitalario Universitario de Vigo, Vigo, Spain, ³⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico, ³⁶Rheumatology Division, Hospital Doctor Negrin, Las Palmas GC, Spain, ³⁷Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France, Paris, France, ³⁸Rheumatology, Medical University Vienna, Vienna, Austria, ³⁹University of Occupational and Environmental Health, Kitakyushu, Japan, ⁴⁰Rheumatology Unit, 1st Dept. of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Athens University Medical School, Athens, Greece, ⁴¹Centro Hospitalar do Porto, University of Porto, Porto, Portugal, ⁴²University of Leeds, Leeds, United Kingdom, ⁴³Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁴⁴Department of Rheumatology, Marmara University, Istanbul, Turkey, ⁴⁵New Zealand Ministry of Health, New Zealand Ministry of Health, Auckland, New Zealand, ⁴⁶Charité Universitätsmedizin Berlin, Berlin, Germany, ⁴⁷Rheumatology, Mount Sinai Hospital and University Health Network, Toronto, ON, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: SLE and classification criteria

Session Information

Date: Wednesday, October 24, 2018

Title: 6W010 ACR Abstract: SLE–Clinical V: Biomarkers, Criteria, & Outcomes (2928–2933)

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose: Correct classification of patients with systemic lupus erythematosus (SLE) is critical for clinical trials and clinical and translational science. The ACR 1997 criteria were criticized for their suboptimal sensitivity. The Systemic Lupus International Cooperating Clinics (SLICC) 2012 criteria increased sensitivity, but at the price of reduced specificity. This and further advances in the field led to the current four phase SLE criteria project. Following an item generation phase and item reduction via a Delphi and a nominal group exercise (1), the provisional criteria were derived from a multicriteria decision analysis exercise (2). These criteria were hence simplified and validated in a large international cohort.

Methods: A large international cohort of 2,321 patients was collected from 23 SLE expert centers, contributing up to 100 patients with SLE and with non-SLE, each. Diagnoses were verified by 3 independent reviewers for 1,193 SLE and 1,059 non-SLE patients. 501 randomly selected SLE and 500 non-SLE patients formed the derivation cohort. All other patients with confirmed SLE or non-SLE diagnosis formed the validation cohort. Sensitivity and specificity were compared to the ACR 1997 and the SLICC 2012 criteria.

Results: The criteria were fine-tuned and simplified, using ANA of ≥1:80 as entry criterion and a classification threshold of 10. Items can only be counted for classification if there is no more likely cause, and at least one clinical item must be present.

Renal	Class III/IV nephritis	10	Class II/V nephritis	8	Proteinuria ≥0.5 g/day	4
Specific antibodies	Anti-Sm or Anti-dsDNA	6
Muco-cutaneous	ACLE	6	SCLE or DLE	4	Alopecia or oral ulcers	2
Serosa	Acute pericarditis	6	Effusion	5
Musculo-skeletal	Arthritis	6
CNS	Seizures	5	Psychosis	3	Delirium	2
Blood	Autoimmune hemolysis or thrombocytopenia	4	Leukopenia	3
Complement	Low C3 and C4	4	Low C3 or C4	3
Anti-phospholipid	Anti-Cardiolipin or anti-β2-GPI or lupus anticoagulant	2
Constitutional	Fever	2

Sensitivity was close to the SLICC 2012 criteria, specificity maintained at the level of the ACR 1997 criteria. This performance was independently confirmed in the validation cohort.

	ACR 1997 criteria	SLICC criteria	New criteria
Derivation
Sensitivity	84.63	96.81	98.00
Specificity	95.20	90.00	96.40
Validation
Sensitivity	82.76	96.70	96.12
Specificity	93.38	83.62	93.38

Conclusion: The novel set of criteria reached the goal of improved sensitivity close to the SLICC 2012 criteria, while maintaining the specificity of the ACR criteria.

Funding note: This project is jointly supported by the ACR and EULAR, but the final criteria have not yet been reviewed or approved by either organization.

References: (1) Aringer et al. Ann Rheum Dis 2017;76 (S2):4; (2) Tedeschi et al. Arthritis Rheumatol 2017; 69 (S10):#1589

Disclosure: M. Aringer, None; K. Costenbader, Alkermes, 1,Cel-Sci Corp, 1,Merck & Co., 2,AstraZeneca, 5,NIH, 2,Lupus Foundation of America, 6,Pfizer, Inc., 9,GlaxoSmithKline, 5, 9; R. Brinks, None; D. Boumpas, None; D. Daikh, None; D. Jayne, None; D. L. Kamen, None; M. Mosca, None; R. Ramsey-Goldman, None; J. S. Smolen, None; D. Wofsy, None; B. Diamond, None; S. Jacobsen, None; W. J. McCune, None; G. Ruiz-Irastorza, None; M. Schneider, None; M. Urowitz, None; G. Bertsias, None; B. Hoyer, None; N. Leuchten, None; C. Tani, None; S. K. Tedeschi, None; Z. Touma, None; B. Anic, None; F. Assan, None; T. M. Chan, None; A. E. Clarke, Bristol-Myers Squibb, 5,AstraZeneca, 5,Exagen Diagnostics, 5,AstraZeneca, 9,Celgene Corporation, 9; P. Crow, None; L. Czirják, None; A. Doria, None; W. Graninger, None; B. Halda-Kiss, None; S. A. Hasni, None; P. M. Izmirly, None; M. Jung, None; G. Kumanovics, None; X. Mariette, None; I. Padjen, None; J. Pego-Reigosa, None; J. Romero-Díaz, None; I. Rúa-Figueroa, None; R. Seror, None; G. Stummvoll, None; Y. Tanaka, None; M. Tektonidou, None; C. Vasconcelos, None; E. M. Vital, None; D. J. Wallace, None; S. Yavuz, None; R. P. Naden, None; T. Dörner, None; S. Johnson, Roche, Bayer, Boehringer, BMS, NIH, Merck, 9.

To cite this abstract in AMA style:

Aringer M, Costenbader K, Brinks R, Boumpas D, Daikh D, Jayne D, Kamen DL, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Diamond B, Jacobsen S, McCune WJ, Ruiz-Irastorza G, Schneider M, Urowitz M, Bertsias G, Hoyer B, Leuchten N, Tani C, Tedeschi SK, Touma Z, Anic B, Assan F, Chan TM, Clarke AE, Crow P, Czirják L, Doria A, Graninger W, Halda-Kiss B, Hasni SA, Izmirly PM, Jung M, Kumanovics G, Mariette X, Padjen I, Pego-Reigosa J, Romero-Díaz J, Rúa-Figueroa I, Seror R, Stummvoll G, Tanaka Y, Tektonidou M, Vasconcelos C, Vital EM, Wallace DJ, Yavuz S, Naden RP, Dörner T, Johnson S. Validation of New Systemic Lupus Erythematosus Classification Criteria [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/validation-of-new-systemic-lupus-erythematosus-classification-criteria/. Accessed .

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