medwireNews: Achievement of LLDAS is associated with a significant reduction in mortality risk among people with systemic lupus erythematosus (SLE), study findings suggest.
This risk reduction was similar to that associated with remission, but the researchers report “[s]trikingly greater” decreases in mortality risk when using alternative definitions of remission with lower thresholds of glucocorticoid exposure, while glucocorticoid-free remission was “most protective of all.”
The results “validate LLDAS as a treat-to-target endpoint that combines attainability and utility,” but “strongly support glucocorticoid-free remission as the ultimate goal of therapy for patients with SLE,” write Eric Morand (Monash University, Clayton, Victoria, Australia) and colleagues in The Lancet Rheumatology.
The study included 3811 people (92.1% women) with SLE who were included in the Asia Pacific Lupus Collaboration cohort in 2013–2020. A total of 80.8% of these individuals achieved LLDAS and 63.9% achieved remission at least once during a median follow-up of 2.8 years, while the average proportion of time spent in LLDAS and remission was 50.0% and 25.9%, respectively.
Morand and team found that the proportion of patients achieving LLDAS at least once was significantly lower among the 80 individuals who died during the study than the 3731 who were alive at follow-up (54.4 vs 81.4%), and those who died were significantly less likely to be in LLDAS for at least half of the observation period (27.8 vs 52.7%).
Multivariable analysis demonstrated that people who were in LLDAS for at least half of the time had a significantly lower risk for mortality than those who were not, with a hazard ratio (HR) of 0.51 after adjustment for smoking, gross domestic product, and Systemic Lupus International Collaborating Clinics–American College of Rheumatology Damage Index score.
A similar association was observed for being in remission for at least half the time (HR=0.52), when remission was defined as a clinical SLEDAI score of 0, a physician global assessment score of less than 0.5, prednisolone dose of 5 mg/day or less, and use of antimalarials and standard maintenance doses of immunosuppressants.
However, this association was strengthened when the researchers defined remission using the more stringent glucocorticoid dose threshold of less than 5 mg/day (ie, excluding patients on a 5 mg/day dose), with a significant HR of 0.31, and this was strengthened further, to a significant HR of 0.13, for glucocorticoid-free remission.
Writing in an accompanying comment, Daniel Wallace (Cedars-Sinai Medical Center, Los Angeles, California, USA) says that although the results are “important and relevant,” the study had several caveats, including a short duration of follow-up and limited generalizability given that only 3.6% of patients were on biologic medications.
He also notes that “[i]nterestingly, the most common cause of death was overwhelmingly related to infections,” which were responsible for 69.6% of the 69 deaths with a reported cause.
This “suggests that SLE was largely reversible until a major clinical complication occurred,” he adds.
The commentator points out that “[s]everal components of LLDAS are currently undergoing revision,” and believes that its use “will become more relevant in clinical settings if prospective studies show that it is a resilient measurement of the disease course of SLE that is sensitive to change.”
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Lancet Rheumatol 2022; doi:10.1016/S2665-9913(22)00304-6
Lancet Rheumatol 2022; doi:10.1016/S2665-9913(22)00310-1