Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune disease with a host of manifestations and a range of severity. Two major rheumatology associations have developed and validated SLE classification criteria in the past: the American College of Rheumatology (ACR) in 1982 with an update in 1997, and the Systemic Lupus International Collaborating Clinics (SLICC) in 2012.

Brigham and Women’s Hospital rheumatology investigators Sara K. Tedeschi, MD, MPH, and Karen H. Costenbader, MD, MPH, have been integrally involved in a multiphase, international effort sponsored by the European League Against Rheumatism (EULAR) and the ACR to develop new SLE classification criteria. The goal is to develop a scoring system that is both highly sensitive and highly specific for SLE, allowing researchers to identify patients with SLE with a high degree of likelihood who can be evaluated in clinical studies, without including patients whose diseases mimic SLE. The new system is intended to be user-friendly in the form of a website or phone app, and relatively easy to use for busy SLE investigators.

In 2014, EULAR and ACR jointly commissioned a 12-member SLE Classification Criteria Steering Committee, on which Dr. Costenbader serves, to develop the new SLE classification criteria system. The multinational project has involved over 150 lupus centers and clinical experts. Rather than requiring a minimum number of criteria be present for SLE classification, the new system will assign different weights to each criterion and will calculate a score for each patient based on the combination of criteria fulfilled. The first phase included item generation (the development of a long list of potential classification criteria), followed by criteria reduction through Delphi and nominal group technique exercises. Drs. Tedeschi and Costenbader orchestrated the third, data-driven phase, and with co-authors they recently published a manuscript describing this process. This work was also presented at the EULAR 2017 Annual Congress and the ACR 2017 Annual Scientific Meetings.

As Drs. Tedeschi and Costenbader discuss in their manuscript, Phase III started with a literature review of the sensitivity and specificity of candidate criteria for SLE. Part of the challenge in interpreting these data is the use of different comparator populations in the various studies, which affects specificity. Dr. Tedeschi presented the literature review results to the SLE Classification Criteria Steering Committee at EULAR 2016. Through iterative discussions over the next five months, criteria definitions and the rank-ordering of criteria were refined and finalized. Criteria were organized into seven clinical and three immunologic groups, or “domains”, containing related criteria arranged in order of ascending importance for SLE classification. Using the new SLE classification system, patients can receive points for only one criterion per domain. An international SLE Expert Panel (9 North Americans, 8 Europeans) was assembled and provided with 167 real patient cases for evaluation, a sample of which was then scored to test the usability of the system.

To determine criteria weights during an in-person meeting at ACR 2016, the SLE Expert Panel participated in a multicriteria decision analysis exercise. This exercise posed a series of pairwise decisions comparing two patients with different criteria in two domains. Experts anonymously voted for the combination of criteria more likely to be SLE; votes were discussed until consensus was reached for each pairwise comparison. Using these decisions, a software program calculated criteria weights and assigned a score to each of the remaining patient cases. Experts reviewed the patient case scores and found that the calculated weights for arthritis and cutaneous criteria were inconsistent with expert opinion on the intended weights for those two domains. The SLE Expert Panel subsequently reached consensus on a preliminary threshold score for SLE classification using re-calculated criteria weights.

The fourth and final phase of SLE classification criteria development is currently underway.  This phase involves validation of the preliminary weights and threshold established in Phase III and will be conducted using a larger, international sample of patients with SLE and those with conditions mimicking SLE.

Hundreds of international SLE experts have contributed to the development of the new EULAR/ACR SLE Classification Criteria in a data-driven process. The new criteria system is expected to have greater sensitivity and specificity for classifying SLE for clinical studies than prior sets of classification criteria. Ultimately, this system will result in greater similarity between patients enrolled in SLE clinical studies, and clinicians and researchers will more easily be able to compare and meaningfully assess the results of SLE research studies.