November 10-15

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ACR Convergence 2023

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Home // EULAR, ACR work together on new SLE classification criteria

EULAR, ACR work together on new SLE classification criteria


5 minutes

The ACR is collaborating with the European League Against Rheumatism (EULAR) to develop new classification criteria for systemic lupus erythematosus (SLE).

SLE is challenging to diagnose and treat, with an array of symptoms and signs that are not specific to the disease. Additionally, SLE is among a spectrum of lupus diseases, complicating classification and research.

It is important to note that the new criteria are for the purposes of clinical trials and research only.

Karen H. Costenbader, MD, MPH
Karen H. Costenbader, MD, MPH

“However, it is hoped that if they improve classification of patients as SLE for the purposes of clinical trials of new therapies and clinical research into the causes and outcomes of SLE, in the long term, they will help to improve SLE patient care and outcomes,” said Karen H. Costenbader, MD, MPH, Lupus Program Director in the Division of Rheumatology, Immunology and Allergy at Brigham and Women’s Hospital, Boston.

Dr. Costenbader will be one of three experts who will present EULAR/ACR Classification Criteria Update for SLE on Tuesday morning at 7:30 am in Room 6 C. The symposium will provide an overview of the focus, limitations, and unmet needs of previous SLE classification criteria, highlight the development and validation of the new criteria, and demonstrate their use in real cases.

Martin Aringer, MD, PhD
Martin Aringer, MD, PhD

Also presenting will be Martin Aringer, MD, PhD, Chief of the Division of Rheumatology at University Medical Center Carl Gustav Carus, Technical University of Dresden, Germany.

The 1982 ACR Criteria for the Classification of SLE were updated in 1997 with the addition of antiphospholipid antibodies. More recently, Dr. Aringer said, the 2012 Systemic Lupus International Collaborating Clinics (SLICC) Criteria for SLE Classification introduced two new concepts.

“For the first time with the SLICC criteria, patients were required to be positive for autoantibodies, namely for anti-nuclear antibodies (ANA) or antibodies to double-stranded DNA,” he said. “Secondly, if patients were autoantibody-positive, the SLICC classification criteria could be fulfilled by lupus glomerulonephritis on histology without any other items.”

To understand whether autoantibodies should be required in the classification of SLE, several members of the ACR-EULAR steering committee conducted a rigorous systematic review of the literature and meta-regression analysis that was published earlier this year in Arthritis Care & Research. It was found that an antinuclear antibody titer of >= 1:80 by immunofluorescence on human epithelial type 2 cells had very good sensitivity (98.4% (95% confidence interval [CI] 97.6-99.0%)) for correctly capturing SLE. Consequently, this has been proposed as an “entry criterion,” meaning an individual could not be considered for classification of SLE without it.

Dr. Aringer offers some classical scenarios: “One is a young woman presenting with new onset polyarthritis, no evidence of rheumatoid arthritis, and additional symptoms like myalgias and oral ulcers. If she is ANA negative, it is unlikely that she has SLE. If she turns out to be ANA positive, and several additional features in laboratory tests, such as leukocytopenia, low complements, or antibodies to double-stranded DNA or Sm are present, she would reach the threshold for SLE classification. If she had nephritis, turning out to be class III or IV lupus nephritis, the weight of this item would be sufficient to classify her disease as SLE with positive ANA and the oral ulcers (or any of the laboratory markers) only. A typical case of acute onset SLE, with malar rash, serositis, fever, and laboratory features and a positive ANA >= 1:80 would be classified as SLE.”

Of course, it is hoped that the criteria will translate to more research, drug development, and ultimately, better patient outcomes, the presenters note.

“This is a work in progress, and the final criteria system has yet to be established,” Dr. Costenbader said, noting that “practicality and feasibility” were among the criteria development steering committees’ central goals.

“We hope that these classification criteria will be utilized in all kinds of clinical practices worldwide for conducting clinical research and enrolling subjects into trials,” she said. “Thus, cutting-edge biomarker assays that might be very useful in distinguishing SLE and among SLE subtypes could not be included as they are not widely available. We envision having the new criteria system on a very accessible easy-to-use app that could be used to see whether a person meets classification criteria for SLE for research.”

Sindhu Johnson, MD, PhD
Sindhu Johnson, MD, PhD

Also during this symposium, Sindhu Johnson, MD, PhD, Rheumatologist and Clinical Epidemiologist at the University of Toronto, will discuss the rigorous process of developing the new SLE classification criteria.

“In this multi-phased endeavor, we have employed a balanced use of data-driven and expert-based methods, which also includes the patient perspective,” she said. “Through Delphi and nominal group technique consensus methods; patient cross-sectional survey; multi-criteria decision analysis; establishment of a multi-center early SLE cohort; and separate derivation and validation cohorts—more than 150 investigators and more than 3,000 patients have contributed to this work to date.”

Dr. Johnson also notes that the criteria are intended only for the classification of SLE, not the multiple other types of lupus that fall under the lupus spectrum of diseases.

It is a challenge to develop classification criteria that will define a relatively homogeneous population of individuals with SLE, which is a very heterogeneous autoimmune disease, to a very high degree of certainty, but it is extremely important as the new classification criteria are intended for use in clinical trials where subjects may be exposed to potentially toxic new therapies. Separate classification criteria are underway for cutaneous lupus for the purposes of clinical trials and studies.