Consensus definition of a low disease activity state in systemic lupus erythematosus

Abstract

Background: In systemic lupus erythematosus (SLE), organ damage, morbidity and mortality are the result of acute or sustained disease activity. The diversity of clinical features of active SLE makes quantification of disease activity problematic. The definition of a low disease activity state in rheumatoid arthritis has resulted in it being widely applied in research and clinical practice, but in SLE there is currently no such definition and thus no related outcome data. In contrast, clinicians often intuitively recognize a state of low SLE disease activity, wherein patient Os disease activity is low and treatment burden acceptable. No empirical definition of a low disease activity state in SLE has been described. Objectives: To define a lupus low disease activity state (LLDAS), for subsequent validation using prospective cohort data. Methods: Firstly, we defined LLDAS conceptually as follows: A state which, if sustained, is associated with a low likelihood of adverse outcome, considering both disease activity and medication safety. Next, 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. These items were scored on a 5-point scale, then reduced using the Delphi method. 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. Results: Fifty-six unique items were initially generated. These fell into two domains: (i) descriptions of disease activity, and (ii) descriptions of medication use. Following two rounds of Delphi, unanimous agreement on the preliminary 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 Conclusions: We have generated a definition of LLDAS. The definition of LLDAS will be validated in a large prospective multicentre Asian-Pacific lupus cohort, using outcomes including organ damage and death, and refined in response to subsequent findings. Once validated, LLDAS may serve alone, or in combination with variables such as patient reported outcomes, as a treatment target in SLE clinical practice, research, and clinical trials.