New definition is a great step forward
An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.
Dr. Helena Assunção
A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.
But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.
To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.
“It is not easy to apply,” Dr. Assunção said.
The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).
In contrast, the LLDAS is defined as:
- A SLEDAI-2k score of 4 or less with no major organ involvement
- No new disease activity
- A physician global assessment of the patient of 1 or less on a 0-3 scale
- Maintenance on a prednisolone dosage of 7.5 mg/day or less
- Maintenance on a standard immunosuppressive regimen
A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).
Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.
Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.
The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”
Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.
Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.
The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.
The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.
SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.