Less Stringent SLE Remission Definitions May Be Insufficiently Distinct From LLDAS

Researchers assessed the attainability and effect of the Definitions of Remission in Systemic Lupus Erythematosus (SLE) compared with the lupus low disease activity state in patients with SLE.

The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) criteria vary widely in terms of attainability and utility, depending on their stringency, according to study results published in The Lancet Rheumatology. Among the DORIS definitions of remission, all but 2 definitions were associated with significantly reduced damage accrual, but similar protective effects as lupus low disease activity state (LLDAS); LLDAS was found to be more readily attainable than any remission definition.

Researchers sought to evaluate the attainability and effect on disease outcomes of the DORIS definitions of remission compared with LLDAS in patients with SLE. Primary outcome measure was accrual of irreversible organ damage; secondary outcome was the occurrence of disease flares.

The prospective multicenter cohort study included data from 1707 patients with SLE aged ≥18 years, recruited between May 2013 and December 2016 from 13 international centers of the Asia Pacific Lupus Collaboration and who fulfilled either the 1997 American College of Rheumatology (ACR) criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria. Patients with <2 visits every 6 months were excluded from the study.

Demographic and disease characteristics, including sex, ethnicity, year of SLE diagnosis, and disease manifestations were collected from each patient in the study. Disease activity was measured at every visit using the SLE Disease Activity Index 2000 and physician global assessment.

Researchers used linear models and time-based Cox proportional hazard models for the assessment of DORIS definitions of remission, and damage accrual and disease flares, based on LLDAS. Attainment of remission for each visit was based on the 8 DORIS definitions of remission, varying by serologic activity, glucocorticoid and immunosuppressive agent use.

Of the 1701 patients, 1591 were women (median age at diagnosis, 29 years [interquartile range (IQR), 21-40 years]; median disease duration, 8 years [IQR, 4-14 years]). Patients with SLE were followed for a mean duration of 2.2±0.9 years. Results of the study indicated that while attainment of remission ranged from 4.6% to 35.9% of 12,689 visits, with 11.1% of patients achieving at least 1 episode of definition of remission, according to the DORIS criteria, LLDAS was attained in 6081 visits, with 78.0% of patients achieving at least 1 episode of LLDAS during follow-up.

The least stringent remission definition (definition 3), which allows serologic activity and the use of antimalarial drugs, prednisolone, and immunosuppressive agents had the most overlap with LLDAS in 68.1% of the 6081 visits. The least overlap with LLDAS attainment was the definition of complete clinical and serologic remission without treatment, except with antimalarial drugs (definition 6). Time-dependent analysis showed that certain DORIS remission definitions (definitions 1-4) were associated with significantly reduced damage accrual, however, all definitions of remission were associated with reduced disease flares; highest protective effect was seen in definitions with the absence of serologic activity and prednisolone use.

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Researchers found that remission definitions 1-4, 7, and 8 were significantly associated with protection against damage accrual, with similar effect sizes; the most stringent remission definitions (definitions 5, 6) were not associated with protection against damage accrual.

Remission definitions achieved for ≥50% of observed time were linked to reduced flares. However, LLDAS attainment at any visit was associated with significantly reduced damage accrual or disease flares, and LLDAS for ≥50% of observed time was associated with a 2-fold reduction of risk for flare and damage accrual. Among patients who met the definition for LLDAS but not remission, LLDAS was associated with a significant decrease in damage accrual for all definitions of remission, except the least stringent.

Overall, remission attainment, according to most proposed definitions, was associated with significant reductions in damage accrual and disease flares in patients with SLE, despite definition stringency having an effect on the attainability of remission.

Researchers of the study concluded, “Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.”

Disclosures: This study was funded by UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Golder V, Kandane-Rathnayake R, Huq M, et al. Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study. Lancet Rheumatol. 2019;1:e103-110.