THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Research attempts to clarify concepts of 
incomplete lupus and low disease activity

Karen Costenbader, MD, MPH
Karen Costenbader, MD, MPH

Major gaps exist in understanding how to best diagnose patients with lupus, how to use the classification criteria in clinical trials, and how to measure improvement and remission in the clinical setting. The Tuesday morning session Lupus: Early Diagnosis & Treat to Target will feature a pair of experts who will review these concepts, providing practical guidance to clinicians to help improve patient care. 


The session, which takes place from 9:00 – 10:00 am in the Thomas Murphy Ballroom 3 & 4, Building B in the Georgia World Congress Center, includes Karen Costenbader, MD, MPH, Director of the Lupus Program at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, discussing the development of the new classification criteria for lupus, including the concept of “incomplete lupus” as it pertains to identifying patients who may not meet all of the classification criteria.


“The idea of incomplete lupus is actually a very old concept and is an example of a plethora of confusing nomenclature — pseudo lupus, occult lupus, potential lupus, possible lupus, just to name a few — that we have historically used for cases involving patients below the threshold for SLE classification by the older 1997 criteria,” Dr. Costenbader said. “There’s a big heterogeneity in lupus and in lupus presentation — that’s why there are so many words that we use for these people. We think that if they have early symptoms, they may be developing into lupus.”


A key goal in developing the updated lupus classification criteria, she said, is to provide increased sensitivity and specificity for people with various durations of symptoms and distinguish between those people who fall under the umbrella of lupus-like conditions and early lupus patients who might be actually evolving into classic viable disease.


“Symptom duration is important in being able to separate people who might have incomplete or possible lupus, but have been stable for many years, from people in whom symptoms are just starting but accumulating rapidly and who may be at much higher risk of developing lupus in the future,” Dr. Costenbader said. “Moving forward, we need more study on what happens to people below the threshold for classification over time to develop a better understanding of the development of lupus. If we can identify these early pre-lupus patients and increase our understanding of the heterogeneity of pre-lupus, it will help to provide greater precision medicine opportunities and to develop new medications, new drug targets, and then to test these medications in the right populations.”


Eric Morand, MD, PhD
Eric Morand, MD, PhD

In another presentation, Eric Morand, MD, PhD, Head of Rheumatology at Monash Health and Professor of Medicine at Monash University, Australia, will review the concept of low disease activity in lupus and the implications of this concept for clinical practice.


“Achieving treatment breakthroughs in lupus has been very challenging and the field has seen very few,” Dr. Morand said. “The case has been made that endpoints used in research is a significant part of the reason for this failure because the endpoints that we’ve been using are all more than 20 years old and, in many cases, have not been subject to rigorous validation.”


That issue led to the development of a collaborative group of researchers, now known as the Asia-Pacific Lupus Collaboration, who set out to produce and validate a measure of low disease activity in lupus that could be used in trials and clinical practice.


“We established a process to generate a definition of a lupus low disease activity state (LLDAS) and to do that in the most robust and evidence-based way we could,” Dr. Morand said. “We then tested this in a small retrospective study and found it to have good performance characteristics. After we published it, it was tested retrospectively by many other groups in their cohorts and found to have extremely consistent performance characteristics, which was reassuring.”


The research group recently published the results in a validation study involving more than 1,700 patients in multiple countries and centers in the Asia-Pacific region, who were enrolled prospectively for the purpose of validating the LLDAS measure.


“The results of that study showed that attaining the lupus low disease activity state was powerfully protective against adverse outcomes, including damage accrual and flare,” Dr. Morand said. “Therefore, we think that the low disease activity endpoint is now formally validated and fit for purpose for use in clinical practice and in clinical trials, which means that a treat-to-target approach in lupus can be studied. We believe this opens a new chapter in using evidence-based measures to test new treatments and new treatment strategies in lupus.”