Caveats and pitfalls in defining low disease activity in systemic lupus erythematosus

The treat-to-target strategy has been recently suggested in the management of Systemic Lupus Erythematosus (SLE). Lupus Low Disease Activity State (LLDAS) and Definitions Of Remission In SLE (DORIS) remission were outlined as two concentric targets. The achievement of LLDAS was shown to be associated with lower frequency of SLE flare, decreased damage progression, better quality of life, and reduced mortality. In addition, LLDAS has successfully been tested in post-hoc analyses of a number of randomized controlled trials. However, it has been recently underlined that LLDAS includes a high proportion of patients in remission, raising the question if these endpoints are sufficiently distinct to consider their separation clinically relevant. Some studies suggest that the protective effect of LLDAS on damage might be due to the inclusion of patients who are in remission. Notably, clinical low disease activity (LDA) seems to be uncommon in SLE due to the relapsing-remitting pattern of the disease, in which low level of activity only occurs transiently. Moreover, since the domains included in LLDAS have several limitations, such as the use of a binomial disease activity index, the exclusion of some mild manifestations and the consideration of items subjected to variability (physician global assessment and glucocorticoids dose), not all patients in LDA are adequately represented by LLDAS.