Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus: a multinational prospective cohort study
Document Type
Article
Publication Date
8-1-2024
Abstract
Background Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission. Methods Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time--event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. Findings 3449 patients were followed up for a median of 28 years (IQR 11-56), totalling 37 662 visits. 3180 (922%) patients were women, and 3031 (879%) were of Asian ethnicity. 2506 (727%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 060 95% CI 051-071], p<00001; remission: 066 057-076], p<00001) and flare (LLDAS: 056 051-063], p<00001; remission: 066 060-073], p<00001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS. Interpretation We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission.
Divisions
medicinedept
Funders
AstraZeneca,Bristol-Myers Squibb,Eli Lilly,UCB Pharma SA,EMD Sereno,GlaxoSmithKline,Johnson & Johnson Johnson & Johnson USA Janssen Biotech Inc
Publication Title
Lancet Rheumatology
Volume
6
Issue
8
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS