Background/Purpose:

The definitions of low disease activity state (LDAS) and remission as desirable treatment goals in rheumatoid arthritis have been widely applied in research and clinical practice. In SLE, the measurement of active disease is problematic, and while a definition of remission has been published it was met by <2% of patients (Urowitz, 2007). A definition of ‘lupus low disease activity state’ (LLDAS) could, once validated, be applied as a novel outcome measure in observational and interventional studies. We sought to define LLDAS using consensus methodology, and to perform preliminary validation of LLDAS using prospective data from an SLE cohort. 

Methods:

We defined LLDAS conceptually as ‘a state which, if sustained, is associated with a low likelihood of adverse outcome’, considering both disease activity and medication safety. A panel of experts from Hong Kong, China, Philippines, Thailand, Singapore, Indonesia and Australia individually generated items for potential inclusion in a definition of LLDAS. Using the Delphi method, these items were scored on a 5-point scale and then reduced. Six experts participated in the first round of Delphi, and items with a mean score > 3 were retained. Eleven experts then participated in a consensus meeting using the nominal group technique, and in a second round of Delphi, in which items with a mean score > 4 were retained. The frequency of attainment of LLDAS and its ability to predict accrual of irreversible organ damage (measured using the SDI) was determined in a longitudinally followed cohort of patients with SLE, using logistic regression. 

Results:

Fifty-six ‘unique’ items were initially generated, in two domains: (i) disease activity, and (ii) medication use. Following two rounds of Delphi and a nominal group discussion, unanimous agreement on a definition of LLDAS was reached. The final list of five items defining LLDAS comprised:

1.SLEDAI-2K ≤4, with no SLEDAI activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, hemolytic anemia, fever) and no gastrointestinal activity);

2.  No new features of lupus disease activity compared to the previous assessment;

3. SELENA-SLEDAI physician global assessment (PGA, scale 0-3) ≤1;

4. Current prednisolone (or equivalent) dose ≤ 7.5 mg daily; and

5. Well-tolerated standard maintenance doses of immunosuppressive drugs and/or approved biologic agents, excluding investigational drugs.

Among 192 patients with SLE followed for a median duration of 3.37 years, LLDAS was achieved on at least one occasion by 72%. The median cumulative duration of LLDAS was 245 days.  Patients in whom the cumulative duration of LLDAS was greater than 245 days had significantly less accrual of organ damage during follow up than patients in whom the cumulative LLDAS duration was less than 245 days (SDI (mean±SD) 1.01±1.4 v.1.6±1.9, Mann-Whitney p=0.023, Odds Ratio=0.8, 95% CI: 0.66-0.97, p=0.025). 

Conclusion:

We have generated a definition of LLDAS and shown that LLDAS is a predictor of organ damage in SLE. This definition of LLDAS requires further validation, against outcomes including organ damage and death, in a large prospective multicenter cohort. LLDAS may serve as a treatment target in SLE clinical practice and research.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/consensus-definition-and-preliminary-validation-of-a-low-disease-activity-state-in-systemic-lupus-erythematosus/