TY - JOUR
T1 - Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus
T2 - a multinational prospective cohort study
AU - Golder, Vera
AU - Kandane-Rathnayake, Rangi
AU - Li, Ning
AU - Louthrenoo, Worawit
AU - Chen, Yi Hsing
AU - Cho, Jiacai
AU - Lateef, Aisha
AU - Hamijoyo, Laniyati
AU - Luo, Shue Fen
AU - Wu, Yeong Jian
AU - Navarra, Sandra V.
AU - Zamora, Leonid
AU - Li, Zhanguo
AU - Sockalingam, Sargunan
AU - Katsumata, Yasuhiro
AU - Harigai, Masayoshi
AU - Hao, Yanjie
AU - Zhang, Zhuoli
AU - Basnayake, Duminda
AU - Chan, Madelynn
AU - Kikuchi, Jun
AU - Takeuchi, Tsutomu
AU - Bae, Sang Cheol
AU - Goldblatt, Fiona
AU - Oon, Shereen
AU - O'Neill, Sean
AU - Ng, Kristine
AU - Law, Annie
AU - Tugnet, Nicola
AU - Kumar, Sunil
AU - Tee, Cherica
AU - Tee, Michael
AU - Ohkubo, Naoaki
AU - Tanaka, Yoshiya
AU - Lau, Chak Sing
AU - Hoi, Alberta
AU - Nikpour, Mandana
AU - Morand, Eric F.
AU - on behalf of the Asia Pacific Lupus Collaboration
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/8
Y1 - 2024/8
N2 - 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 in 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-to-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 in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. Findings: 3449 patients were followed up for a median of 2·8 years (IQR 1·1–5·6), totalling 37 662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) 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 0·60 [95% CI 0·51–0·71], p<0·0001; remission: 0·66 [0·57–0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51–0·63], p<0·0001; remission: 0·66 [0·60–0·73], p<0·0001), 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. Funding: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.
AB - 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 in 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-to-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 in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. Findings: 3449 patients were followed up for a median of 2·8 years (IQR 1·1–5·6), totalling 37 662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) 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 0·60 [95% CI 0·51–0·71], p<0·0001; remission: 0·66 [0·57–0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51–0·63], p<0·0001; remission: 0·66 [0·60–0·73], p<0·0001), 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. Funding: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.
UR - http://www.scopus.com/inward/record.url?scp=85197066570&partnerID=8YFLogxK
U2 - 10.1016/S2665-9913(24)00121-8
DO - 10.1016/S2665-9913(24)00121-8
M3 - Article
C2 - 38876129
AN - SCOPUS:85197066570
SN - 2665-9913
VL - 6
SP - e528-e536
JO - The Lancet Rheumatology
JF - The Lancet Rheumatology
IS - 8
ER -