The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) — a tool commonly used to determine disease activity in systemic lupus erythematosus patients — misses nearly two of out three patients with clinically meaningful changes in disease activity, a Portuguese study found.
The study, “Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36–month prospective cohort study of 334 patients,” was published in the journal Lupus.
The SLE Disease Activity Index (SLEDAI) is a global scoring index that encompasses the sum of 24 weighted clinical and laboratory variables. SLEDAI-2K and Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI versions are the most widely used disease activity measures, both in research and in clinical practice.
These are important not only to monitor patients’ responses to treatment, but also for determining if a therapy is effective in clinical trials. However, SLEDAI scores patients irrespective of their symptoms’ severity; for example, a patient with two active joints will have the same score as one with 20 active joints. SLEDAI also fails to score severe lupus manifestations, such as anemia, pneumonitis (lung inflammation), or gastrointestinal symptoms.
This, together with its “inability to demonstrate clinically meaningful improvements in recent trials, despite a positive clinical impression of efficacy, has raised the debate about the performance of SLEDAI in detecting clinically meaningful changes in SLE disease activity,” researchers explained.
So, investigators set out to determine how SLEDAI-2K performed in detecting meaningful disease activity changes in a clinical practice setting. They included 334 patients (mean age 45 years), who had been diagnosed for an average of 11 years.
Participants were followed for 36 months, visited their rheumatologist at least twice each year, and were assessed through the Physician Global Assessment (PGA) score and the SLEDAI-2K index. A clinically meaningful change — improvement or worsening of disease activity — was defined as a 0.3-point difference in PGA and a 4-point difference in SLEDAI-2K.
At study start, the two disease activity scores were in good agreement, researchers reported. However, while 24% of patients had meaningful improvements in disease activity during follow-up, and 15% experienced disease activity worsening according to PGA assessment, the SLEDAI-2K index failed to identify 70% and and 65% of these cases.
These findings demonstrate that “SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity,” being “inadequate for use in clinical practice and research,” researchers wrote.
Collectively, the data showed that SLEDAI-2K index “failed to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening,” they said.
Because most clinical trials in lupus use an improvement of four or more points in the SLEDAI score as a measure of effectiveness — called SLE Responder Index 4 (SRI4) — the findings “have major implications in the interpretation of clinical trials applying SRI4 as the primary endpoint,” researchers explained.
“There is a need for more sensitive SLE disease activity measures in clinical practice and research,” they concluded.