Sindhu Johnson, MD, PhD, on the 2019 EULAR/ACR Classification Criteria for SLE
Classification criteria are used to identify homogeneous groups of patients for inclusion in research studies and clinical trials.
The previous classification criteria for lupus—the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria1—addressed mucocutaneous and neuropsychiatric manifestations, defined SLE as an autoantibody disease, and more, in an effort to improve clinical relevance, ensure that individuals meet methodology requirements, and incorporate new insight regarding the immunology of SLE.
Still, the understanding of SLE has advanced over time, prompting an update to the classification criteria for SLE.
Rheumatology Consultant caught up with Sindhu Johnson, MD, PhD, director of the Toronto Scleroderma Program at University Health Network in Ontario, Canada, and coauthor of the new criteria,2 about how the criteria have changed over time and how it will impact overall management of the condition.
Rheumatology Consultant: What prompted development of the new classification criteria for SLE?
Sindhu Johnson: SLE is a heterogeneous condition with a wide variety of presentations. The ACR and EULAR have long identified the need for classification criteria to help identify more homogeneous groups of patients for inclusion in research studies. There had been two widely used criteria sets in the past. At the initiation of this project, the feeling was that it would be ideal if there was one set of criteria that everyone could use. At the same time, there had been shifts in our understanding and thinking about lupus since the publication of the previous two criteria sets. We wanted a criteria set that had a very high specificity, as well as one that would be useful in classifying early disease.
RHEUM CON: How do the new criteria differ from the 2012 criteria?
SJ: First, antinuclear antibodies have always been identified as an important feature of lupus. In clinical practice, it is often used as a screening test. In the new EULAR/ACR criteria, antinuclear antibodies have been repositioned as an entry criterion. This means that they need to have been present at any point in time for one to apply the new criteria set. Second, the criteria have been weighted. This is a reflection of physician thinking in that some disease manifestations are weighted more heavily than others when we try to classify a patient. Third, once we achieved the weight, we recognized that there is a hierarchy within each domain in that if there are a number of features within the domain, we should only include the most heavily weighted criteria. Lastly, we found it within the domain of lupus nephritis that not all lupus nephritis is considered equal, and some forms are weighted more heavily. Together, the new criteria set has been found to have a higher specificity than the 2012 SLICC criteria. Our criteria set is simplified in that some of the lower-frequency items—that is, items that occur less frequently in clinical practice—are not included. However, a novel feature such as fever is included in the criteria set. This is so because we found that fever is an important criterion among patients who present early in their disease.
RHEUM CON: What are the most important changes to the criteria that rheumatologists should know about?
SJ: Classification criteria are not diagnostic criteria. The diagnosis of lupus is still in the hands of the trained physician. This criteria set is not the complete list of all the manifestations of lupus. A patient may present with other features that are not included in this list. The classification criteria should not preclude a diagnosis. Most importantly, payers should not use classification criteria as a justification to withhold (payment for) treatment from patients who need it. The structure and format of the new criteria are more reflective of the way clinicians currently think about lupus. It also has an excellent balance of sensitivity and specificity. This reduces the risk of misclassification—that is, appropriately identifying those who have the disease and not identifying someone as having lupus when they do not. Finally, these criteria may be useful for identifying patients with early disease. We hope this will lead to clinical trials looking at prevention or management of patients early on in the disease course.
RHEUM CON: Will the criteria change again in the future?
SJ: Criteria sets should reflect changes in our understanding of the disease. On the horizon, I would imagine that with advancing knowledge we will be able to include proteomics, metabolomics, and genomics data. Hopefully, we can one day include molecular or biological classification of disease. We strongly considered this during the development of this criteria set; however, we are not quite there yet. I fully expect that in the future we will be able to include molecular or biological classification of lupus.
RHEUM CON: What are the key takeaway messages from the new criteria for rheumatologists?
SJ: This is the largest international lupus classification project. The development and validation of this criteria set involved over 200 investigators from a variety of medical specialties and methodologies, patient advocates, and more than 4000 patients. These criteria reflect a paradigm shift in lupus classification for identifying patients for inclusion in research studies. We believe it is a more accurate reflection of the way clinicians think about lupus, particularly the use of an entry criterion, the weighting of criteria, and the hierarchical nature of the criteria. We also think that attribution is a critical component of this criteria set; the criteria should only be included if it is best explained by lupus and not explained better by another disease.
- Petri M, Orbai A-M, Alarcón GS, et al. Derivation and validation of Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi:10.1002/art.34473.
- Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151-1159. doi:10.1136/annrheumdis-2018-214819.