Validation of a novel definition of low disease activity state in systemic lupus erythematosus

Abstract

The principle of “Treating-to-target” has been widely applied to the management of rheumatic diseases including systemic lupus erythematosus (SLE). Yet, there is currently not an internationally agreed definition of low disease activity in lupus. In 2015, the Asia-Pacific Lupus Collaboration presented a novel consensus definition of a safe state in lupus, the “Lupus Low Disease Activity State” (LLDAS), defined as:

1. SLE Disease activity Index (SLEDAI-2k) ≤4, with no SLEDAI activity in major organ systems (renal, centralnervous system, cardiopulmonary, vasculitis, haemolytic anaemia, fever) and no gastrointestinal activity; 2. No new features of lupus disease activity compared to the previous assessment; 3. SELENA-SLEDAI physician global assessment ≤1; 4. Current prednisolone (or equivalent) dose ≤ 7.5 mg daily; and 5. Well-tolerated standard maintenance doses of immunosuppressive agents and/or approved biologics.

A prospective study was carried out to determine whether LLDAS would predict lower future flare-ups, damage and mortality. 339 patients with lupus as defined by the 1997 ACR criteria or the 2012 SLICC criteria were recruited before 31st October 2013 from the Rheumatology Division of the Queen Mary Hospital of Hong Kong and followed up during the period October 2013 – April 2016. Multivariable binomial regression was used to determine the factors associated with LLDAS and Cox proportional hazard model was used to determine whether prior higher percentage of days in LLDAS would be associated with lower future flare-ups. Mean patient age was 48.1 years and mean disease duration was 19.6 years. All patients were ethnic Chinese and 93.8% were females. There were 79 documented flare-ups in study period. 92.6% of patients have ever achieved LLDAS in the study period and 62.1% of patient-days were in LLDAS. No major epidemiological or particular prior disease presentations were found to be associated with the attainment of LLDAS. Patients with prior higher percentage of days in LLDAS were having lower hazard of lupus flare-ups (HR = 0.420, p = 0.015) after adjustment for gender and age. The numbers of patient damage and death were insufficient for analysis. In conclusion, LLDAS is an independent construct achievable by most patients with different history or background. It can predict the risk of future flare-up, hence reflecting patients with a relatively safer course of disease in this locality. Further studies are needed to determine whether it is associated less lupus-related damage and mortality.