Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study

被引:125
作者
Golder, Vera [1 ]
Kandane-Rathnayake, Rangi [1 ]
Huq, Moth [2 ]
Nim, Hieu T. [1 ]
Louthrenoo, Worawit [3 ]
Luo, Shue Fen [4 ]
Wu, Yeong-jian Jan [4 ]
Lateef, Aisha [5 ]
Sockalingam, Sargunan [6 ]
Navarra, Sandra, V [7 ]
Zamora, Leonid [7 ]
Hamijoyo, Laniyati [8 ]
Katsumata, Yasuhiro [9 ]
Harigai, Masayoshi [9 ]
Chan, Madelynn [10 ]
O'Neill, Sean [11 ,12 ]
Goldblatt, Fiona [13 ,14 ]
Lau, Chak Sing [15 ]
Li, Zhan Guo [16 ]
Hoi, Alberta [1 ]
Nikpour, Mandan [2 ]
Morand, Eric F. [1 ]
机构
[1] Monash Univ, Sch Clin Sci, Melbourne, Vic, Australia
[2] Univ Melbourne, Dept Rheumatol, Melbourne, Vic, Australia
[3] Chiang Mai Univ, Dept Internal Med, Chiang Mai, Thailand
[4] Chang Gung Mem Hosp, Dept Rheumatol Allergy & Immunol, Guishan Township, Taiwan
[5] Natl Univ Singapore Hosp, Rheumatol Div, Singapore, Singapore
[6] Univ Malaya, Dept Med, Kuala Lumpur, Malaysia
[7] Univ Santo Tomas Hosp, Joint & Bone Ctr, Manila, Philippines
[8] Univ Padjadjaran, Dept Internal Med, Bandung, Indonesia
[9] Tokyo Womens Med Univ, Inst Rheumatol, Tokyo, Japan
[10] Tan Tock Seng Hosp, Dept Rheumatol Allergy & Immunol, Singapore, Singapore
[11] Univ New South Wales, South Western Sydney Clin Sch, Sydney, NSW, Australia
[12] Ingham Inst Appl Med Res, Liverpool, NSW, Australia
[13] Royal Adelaide Hosp, Dept Rheumatol, Adelaide, SA, Australia
[14] Flinders Med Ctr, Dept Rheumatol, Bedford Pk, SA, Australia
[15] Univ Hong Kong, Div Rheumatol & Clin Immunol, Hong Kong, Peoples R China
[16] Peking Univ, Dept Rheumatol & Immunol, Peoples Hosp, Hlth Sci Ctr, Beijing, Peoples R China
关键词
TIGHT CONTROL; CLASSIFICATION; DEFINITION; REMISSION; CRITERIA; COLLEGE; BLIND; LLDAS; SLE;
D O I
10.1016/S2665-9913(19)30037-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Treat-to-target strategies have improved outcomes in single-organ diseases with simple clinical or laboratory endpoints. A lack of validated endpoints has prevented adoption of treat to target for complex multiorgan conditions, such as systemic lupus erythematosus (SLE). We report the first prospective study undertaken to specifically validate a treat-to-target endpoint for SLE. Methods In this prospective cohort study, patients aged 18 years or older with SLE were recruited from 13 centres in eight countries and followed prospectively. Patients with at least two visits over the study period no more than 6 months apart were included in the longitudinal analysis. Patients with no visits in the final year of the study were censored from their last visit. Attainment of the lupus low disease activity state (LLDAS) was assessed at each visit. The primary outcome measure was accrual of irreversible end-organ damage, defined as at least a 1-point increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We used time-dependent hazard regression models and generalised linear models to measure the association between LLDAS (attainment at any timepoint, cumulative time in LLDAS, and sustained LLDAS) with accrual of irreversible end-organ damage or flare (key secondary outcome). This study is registered with ClinicalTrials.gov, NCT03138941. Findings Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited and followed for a mean of 2.2 years (SD 0.9), totalling 12689 visits. Attainment of LLDAS at any timepoint was associated with reduction in damage accrual (hazard ratio 0.59, 0.45-0.76; p<0 .0001) and subsequent flare (0.65, 95% CI 0.56-0-75; p<0.0001). Cumulative time in LLDAS was associated with improved outcomes: compared with patients with less than 50% of observed time in LLDAS, those with at least 50% of observed time in LLDAS had reduced risk of damage accrual (0.54, 0.42-0-70; p<0.0001) and flare (0.41, 0.35-0.48; p<0.0001). Similarly, increased durations of sustained LLDAS were associated with incremental reductions in the risk of damage accrual. The association of LLDAS with reduced damage accrual was observed regardless of pre-existing damage or disease activity at study entry. Interpretation LLDAS attainment is associated with significant protection against flare and damage accrual in SLE. These findings validate LLDAS as an endpoint for clinical studies in SLE. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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收藏
页码:E95 / E102
页数:8
相关论文
共 30 条
[1]   Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort [J].
Bruce, Ian N. ;
O'Keeffe, Aidan G. ;
Farewell, Vern ;
Hanly, John G. ;
Manzi, Susan ;
Su, Li ;
Gladman, Dafna D. ;
Bae, Sang-Cheol ;
Sanchez-Guerrero, Jorge ;
Romero-Diaz, Juanita ;
Gordon, Caroline ;
Wallace, Daniel J. ;
Clarke, Ann E. ;
Bernatsky, Sasha ;
Ginzler, Ellen M. ;
Isenberg, David A. ;
Rahman, Anisur ;
Merrill, Joan T. ;
Alarcon, Graciela S. ;
Fessler, Barri J. ;
Fortin, Paul R. ;
Petri, Michelle ;
Steinsson, Kristjan ;
Dooley, Mary Anne ;
Khamashta, Munther A. ;
Ramsey-Goldman, Rosalind ;
Zoma, Asad A. ;
Sturfelt, Gunnar K. ;
Nived, Ola ;
Aranow, Cynthia ;
Mackay, Meggan ;
Ramos-Casals, Manuel ;
van Vollenhoven, Ronald F. ;
Kalunian, Kenneth C. ;
Ruiz-Irastorza, Guillermo ;
Lim, Sam ;
Kamen, Diane L. ;
Peschken, Christine A. ;
Inanc, Murat ;
Urowitz, Murray B. .
ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (09) :1706-1713
[2]  
Castrejón I, 2014, CLIN EXP RHEUMATOL, V32, pS85
[3]  
Dolgin E, 2019, NAT BIOTECHNOL, V37, P6
[4]   Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL) [J].
Francisco Ugarte-Gil, Manuel ;
Wojdyla, Daniel ;
Pons-Estel, Guillermo J. ;
Catoggio, Luis J. ;
Drenkard, Cristina ;
Sarano, Judith ;
Berbotto, Guillermo A. ;
Borba, Eduardo F. ;
Inoue Sato, Emilia ;
Tavares Brenol, Joao C. ;
Uribe, Oscar ;
Ramirez Gomez, Luis A. ;
Guibert-Toledano, Marlene ;
Massardo, Loreto ;
Cardiel, Mario H. ;
Silveira, Luis H. ;
Chacon-Diaz, Rosa ;
Alarcon, Graciela S. ;
Pons-Estel, Bernardo A. .
ANNALS OF THE RHEUMATIC DISEASES, 2017, 76 (12) :2071-2074
[5]   Definition and initial validation of a Lupus Low Disease Activity State (LLDAS) [J].
Franklyn, Kate ;
Lau, Chak Sing ;
Navarra, Sandra V. ;
Louthrenoo, Worawit ;
Lateef, Aisha ;
Hamijoyo, Laniyati ;
Wahono, C. Singgih ;
Chen, Shun Le ;
Jin, Ou ;
Morton, Susan ;
Hoi, Alberta ;
Huq, Molla ;
Nikpour, Mandana ;
Morand, Eric F. .
ANNALS OF THE RHEUMATIC DISEASES, 2016, 75 (09) :1615-1621
[6]   A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus [J].
Furie, Richard ;
Petri, Michelle ;
Zamani, Omid ;
Cervera, Ricard ;
Wallace, Daniel J. ;
Tegzova, Dana ;
Sanchez-Guerrero, Jorge ;
Schwarting, Andreas ;
Merrill, Joan T. ;
Chatham, W. Winn ;
Stohl, William ;
Ginzler, Ellen M. ;
Hough, Douglas R. ;
Zhong, Z. John ;
Freimuth, William ;
van Vollenhoven, Ronald F. .
ARTHRITIS AND RHEUMATISM, 2011, 63 (12) :3918-3930
[7]  
Gladman DD, 2000, J RHEUMATOL, V27, P373
[8]   Does expert opinion match the operational definition of the Lupus Low Disease Activity State (LLDAS)? A case-based construct validity study [J].
Golder, Vera ;
Huq, Molla ;
Franklyn, Kate ;
Calderone, Alicia ;
Lateef, Aisha ;
Lau, Chak Sing ;
Lee, Alfred Lok Hang ;
Navarra, Sandra Teresa V. ;
Godfrey, Timothy ;
Oon, Shereen ;
Hoi, Alberta Yik Bun ;
Morand, Eric Francis ;
Nikpour, Mandana .
SEMINARS IN ARTHRITIS AND RHEUMATISM, 2017, 46 (06) :798-803
[9]   Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study [J].
Golder, Vera ;
Kandane-Rathnayake, Rangi ;
Hoi, Alberta Yik-Bun ;
Huq, Molla ;
Louthrenoo, Worawit ;
An, Yuan ;
Li, Zhan Guo ;
Luo, Shue Fen ;
Sockalingam, Sargunan ;
Lau, Chak Sing ;
Mok, Mo Yin ;
Lateef, Aisha ;
Franklyn, Kate ;
Morton, Susan ;
Navarra, Sandra Teresa V. ;
Zamora, Leonid ;
Wu, Yeong-Jian ;
Hamijoyo, Laniyati ;
Chan, Madelynn ;
O'Neill, Sean ;
Goldblatt, Fiona ;
Nikpour, Mandana ;
Morand, Eric Francis .
ARTHRITIS RESEARCH & THERAPY, 2017, 19
[10]   Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort [J].
Golder, Vera ;
Kandane-Rathnayake, Rangi ;
Hoi, Alberta Yik-Bun ;
Huq, Molla ;
Louthrenoo, Worawit ;
An, Yuan ;
Li, Zhan Guo ;
Luo, Shue Fen ;
Sockalingam, Sargunan ;
Lau, Chak Sing ;
Lee, Alfred Lok ;
Mok, Mo Yin ;
Lateef, Aisha ;
Franklyn, Kate ;
Morton, Susan ;
Navarra, Sandra Teresa V. ;
Zamora, Leonid ;
Wu, Yeong-Jian ;
Hamijoyo, Laniyati ;
Chan, Madelynn ;
O'Neill, Sean ;
Goldblatt, Fiona ;
Morand, Eric Francis ;
Nikpour, Mandana .
ARTHRITIS RESEARCH & THERAPY, 2016, 18