New ACR, EULAR Criteria Distinguish Lupus From Imitators

Damian McNamara

November 09, 2017

SAN DIEGO — New classification criteria for systemic lupus erythematosus (SLE), designed to more accurately identify patients for inclusion in clinical trials, demonstrate improved sensitivity and specificity, experts presenting a preview of the criteria said here at the American College of Rheumatology (ACR) 2017 Annual Meeting.

"SLE is a heterogeneous disease, a disease without a gold standard for diagnosis," said Sindhu Johnson, MD, PhD, from the University of Toronto.

Patients can present with skin, joint, lung, or kidney problems, which can make it difficult to distinguish from other conditions, she explained.

The new criteria — the result of an international collaboration between the ACR and the European League Against Rheumatism (EULAR) — promote earlier identification of lupus, allow researchers to study more homogenous groups of patients, and could drive the development of more effective treatments.

The criteria also recognize that a global consensus on lupus is warranted. "We are moving toward more international collaboration studies," Dr Johnson said during a news conference at the meeting.

Complicated Criteria

The criteria start with a requirement that patients have antinuclear antibody levels of at least 1:80 on a HEp-2 immunofluorescence assay, said Karen Costenbader, MD, from Brigham and Women's Hospital in Boston, during a standing-room only session.

There are 10 domains: seven clinical and three immunologic. Each domain contains multiple items, but only the most heavily weighted one counts toward the scoring for that domain, she explained.

For example, "in early cohort studies, we realized fever may be able to differentiate lupus from other conditions," said Dr Johnson. "But kidney involvement is very important, so fever is weighted far less than kidney involvement."

Patients with a score of at least 10 are considered to have systemic lupus erythematosus. "It sounds a bit cumbersome," Dr Costenbader acknowledged.

"It is a somewhat complicated system, but we're in 2017, so we'll go to an app or a website," she said. "You will not have to memorize the new criteria," she assured the audience. "That is the good news."

The weighting of different items is a new feature for lupus classification. Previous ACR criteria treated all items equally. So too does the Systemic Lupus International Collaborating Clinics (SLICC) criteria, except that lupus nephritis is three times more influential than other items.

"Interestingly," after looking at the data, "it would appear that a number of classic lupus manifestations do distinguish SLE from mimickers — notably, kidney disease, oral ulcers, pleuritis, and alopecia," said Dr Johnson. But nonclassic manifestations that are generally considered to be less specific, such as arthralgia, fever, and fatigue, "also differentiate early SLE from conditions that closely mimic it."

The criteria are based not only on expert opinion and data, but also on patient experience, she added. In fact, because one of the goals of the new classification system is to distinguish lupus from mimickers earlier in the course of disease, the investigators asked patients what symptoms they had when they first developed systemic lupus erythematosus.

But classification criteria are not the same as diagnostic criteria, Dr Johnson emphasized.

Classification Is Not Diagnosis

The diagnosis of systemic lupus erythematosus "still rests in the hands of clinicians." Dr Costenbader said. "We're relying on your clinical acumen here."

The new criteria, which emphasize clinical judgment, stipulate that symptoms only be attributed to lupus when there is no better explanation. In other words, if infection, malignancy, an endocrine disorder, or something else more likely explains a patient's presentation, it is not considered lupus.

At this point, the take-home message for clinicians is that these criteria "should be there to guide them. These are telling us about a phenotype of patients," said news conference moderator Bryant England, MD, from the University of Nebraska Medical Center in Omaha.

"What is needed are clinical trials to identify the same phenotypes, so when we say 'red', you know a red is red," he told Medscape Medical News. "Of course, you can't replace the clinician."

Diagnosis should remain individualized to guide therapy and prognosis, said Martin Aringer, MD, from the Technical University Dresden in Germany, who is the EULAR lead on the new criteria.

"Classification is an absolute requirement for SLE clinical trials, and for clinical and translational studies, if we want to develop new drugs," he pointed out.

"ACR criteria have been great, and still are. The SLICC criteria have advanced the field and are absolutely right still. So improvement on both was a real challenge for us," Dr Aringer told Medscape Medical News.

"When we tested the criteria in the derivation cohort, we had a sensitivity of 98% and a specificity of 97%," Dr Johnson reported. This sensitivity is better than previous criteria and "more accurately reflects our understanding of this disease."

An "Unbelievable Amount of Work"

These are the first classification criteria jointly developed by the ACR and EULAR, although the two organizations have conferred on clinical guidance that addresses rheumatoid arthritis, gout, and other conditions. The multidisciplinary, multinational effort took 4 years to complete.

"This has been an unbelievable amount of work," said Dr England. The criteria "are very well thought out and methodologically sound." And "it's phenomenal how they incorporated patients."

The 12 experts on the steering committee from North America and Europe "started from scratch" and used a four-phase approach to identify criteria. They then reduced the number of items from 145 to 40, assigned different weights to each criterion, and tested the draft instrument in a randomly selected "derivation cohort" of 500 patients and 500 control subjects. Participants were recruited from 36 international centers, which were each asked to contribute up to 100 patients and 100 control subjects (with mimicker conditions). The committee amassed data on more than 2200 patients.

"We are now in the final stages of open consultation," said Dr Johnson. "If you have any comments, feel free to contact Dr Arigner, myself, or anyone on the steering committee over the next 2 weeks," she told the audience.

The steering committee still has untouched data on more than 1000 patients in reserve for final validation. The final version of the criteria will likely be presented at the EULAR meeting in June 2018, Dr Johnson added.

The development of the SLE classification criteria was jointly funded by the ACR and EULAR. Dr Johnson, Dr Costenbader, Dr England, and Dr Aringer have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2017 Annual Meeting. Presented November 7, 2017.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Damian McNamara @MedReporter

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