Editor’s note: This commentary relates to the story, “.”
While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.
Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence () The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.
We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.
By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.
Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.
Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.