Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study

Golder, Vera; Kandane‐Rathnayake, Rangi; Huq, Molla; Louthrenoo, Worawit; Luo, Shue Fen; Wu, Yeong‐Jian Jan; Lateef, Aisha; Sockalingam, Sargunan; Navarra, Sandra V.; Zamora, Leonid; Hamijoyo, Laniyati; Katsumata, Yasuhiro; Harigai, Masayoshi; Chan, Madelynn; O’Neill, Sean; Goldblatt, Fiona; Lau, Chak Sing; Li, Zhan Guo; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F

doi:10.1016/s2665-9913(19)30048-7

Cited by 39 publications

(25 citation statements)

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“…A multinational collaborative group proposed and preliminarily validated LLDAS as a T2T endpoint [ 15 ]. LLDAS attainment has now been shown in multiple cohort studies to be associated with both reduced damage accrual [ 11 , 15 , 16 ] and improved health-related quality of life [ 18 ], and was recently formally validated in a prospective study [ 17 ]. Recently, LLDAS has been shown to discriminate active treatment from placebo more robustly than most commonly used measures [ 19–21 ], although in the one study reported to date, remission did not [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

et al. 2020

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Objective Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients. Methods Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician’s Global Assessment <0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response. Results Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095]. Conclusion At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE. Trail registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568.

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Section: Discussionmentioning

confidence: 99%

Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

et al. 2020

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“…Several studies have compared the effects of DORIS remission and LLDAS on flares and damage accrual ( Table 2 ) [ 34 , 37–39 , 43 , 44 ]. While both LLDAS and remission were associated with reduced flares and damage [ 34 ], less time was needed in remission to see significant associations (<25% observed time for remission vs 25–50% observed time for LLDAS), suggesting a stronger protective effect of the deeper remission states [ 38 ].…”

Section: Development Of Remission and Lldas Definitions And Their Effmentioning

confidence: 99%

“…While both LLDAS and remission were associated with reduced flares and damage [ 34 ], less time was needed in remission to see significant associations (<25% observed time for remission vs 25–50% observed time for LLDAS), suggesting a stronger protective effect of the deeper remission states [ 38 ]. On the other hand, the stricter definitions of remission were difficult to achieve [ 47 ] and to maintain for more than a single visit (7.1% of patients in complete remission for ≥2 consecutive visits) [ 43 ]. In all but one study, LLDAS was more attainable and sustainable than any remission definition; the exception was described in a monocentric prevalent cohort of Caucasian patients with unusually high rates of remission [ 37 ].…”

Section: Development Of Remission and Lldas Definitions And Their Effmentioning

confidence: 99%

“…LLDAS and remission were shown to be concentric stepwise target states, such that patients who fulfil the criteria for the stricter forms of remission also fulfilled criteria for LLDAS, but not vice versa ( Fig. 1 ) [ 43 ]. Interestingly, a small proportion of patients fulfilled the criteria for CROT but not LLDAS, based on new serological activity from previous assessment (new elevation of antibodies to dsDNA or lowering of complement levels), which is not allowed in LLDAS and not accounted for in CROT ( Fig.…”

Section: Development Of Remission and Lldas Definitions And Their Effmentioning

confidence: 99%

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Treatment targets in SLE: remission and low disease activity state

Golder

Tsang-A-Sjoe

2020

Rheumatology

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Treat-to-target strategies have changed the approach to management of many chronic conditions, with improvements in patient outcomes. The key to success of treat to target is the availability of validated treatment endpoints, which have been difficult to derive for SLE, a condition notorious for its heterogeneity. This review will focus on the development and validation of the definitions of remission in SLE framework and the lupus low disease activity state. Lupus low disease activity state is more attainable than remission, with a stepwise concentric relationship between the target states indicating increasing stringency. Both lupus low disease activity state and definitions of remission in SLE remission have been proven to be associated with reduction in disease flares, reduced risk of accrual of irreversible end organ damage, and improvement in patient reported outcomes. These endpoints have therefore provided the key for the development of a treat-to-target approach in clinical practice in SLE and for the design of future clinical trials.

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“…The definitions of remission in SLE (DORIS) criteria for remission and lupus low disease activity state (LLDAS) criteria from the Asia-Pacific Lupus Collaboration (APLC) for low disease activity were the most accepted and used definitions [5,6]. The LLDAS has been both retrospectively and prospectively validated as being associated with reduced damage accrual in several studies [7][8][9], and found also to be more attainable than remission, whilst being no less protective [10]. With only one prospective validation study previously reported [6], the purpose of the present study was to investigate the frequency and determinants of achieving LLDAS, and the influence of LLDAS on disease flare and damage accrual in a single-center prospective longitudinal cohort of Chinese SLE patients.…”

Section: Introductionmentioning

confidence: 99%

Determinants and protective associations of the lupus low disease activity state in a prospective Chinese cohort

Hao

Oon

et al. 2021

Clin Rheumatol

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Objective To investigate the frequency and determinants of achieving the lupus low disease activity state (LLDAS), and the effect of LLDAS attainment on disease flare and damage accrual in a prospective, single-center cohort of Chinese lupus patients. Methods Baseline and follow-up data from consecutive patients at the Peking University First Hospital were collected from January 2017 to June 2020. Results A total of 185 patients were enrolled, with median (range) disease duration at enrolment of 2.3 (0.8–7.7) years, and median follow-up of 2.2 (1.0–2.9) years. By the end of the study, 139 (75.1%) patients had achieved LLDAS at least once; 82 (44.3%) patients achieved LLDAS for ≥ 50% of observations. Multivariable logistic regression analysis showed that 24-h urinary total protein (UTP; per g) (OR = 0.447, 95%CI [0.207–0.968], p = 0.041), serum creatinine (Scr; per 10 µmol/L) (OR = 0.72, 95%CI [0.52–0.99], p = 0.040), and C3 level (per 100 mg/L) (OR = 1.60, 95%CI [1.18–2.17], p = 0.003) at recruitment had independent negative associations with achieving LLDAS for ≥ 50% of observations. Kaplan–Meier analyses showed a significant reduction in flare rate with increased proportion of time in LLDAS. Attainment of LLDAS in at least 50% of observations was an independent protective factor for damage accrual (OR = 0.19, 95%CI [0.04–0.99], p = 0.049). Conclusions In this prospective Chinese cohort, LLDAS was an attainable goal in clinical practice. Nephritis-related markers (UTP and Scr) and C3 level at recruitment negatively influenced achievement of LLDAS. LLDAS achievement was significantly protective from flare and damage accrual. Key points • Low disease activity status (LLDAS) is an achievable target during SLE treatment in China. Urine protein, serum creatinine, and C3 level at recruitment independently affect LLDAS achievement in this group of Chinese lupus patients. • As a treatment target, LLDAS achievement has a highly protective effect for preventing flare and damage accrual, especially in case of achieving LLDAS for ≥ 50% of observations. • The present results further highlight the practical significance of treat-to-target principle in SLE management (T2T/SLE) and the needs for promoting the application of T2T/SLE in clinical practice as well as exploring the concrete implement strategy.

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Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study

Cited by 39 publications

References 25 publications

Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Treatment targets in SLE: remission and low disease activity state

Determinants and protective associations of the lupus low disease activity state in a prospective Chinese cohort

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