Evaluation of remission definitions for systemic lupus erythematosus

a prospective cohort study

Vera Golder, Rangi Kandane-Rathnayake, Molla Huq, Worawit Louthrenoo, Shue Fen Luo, Yeong Jian Jan Wu, Aisha Lateef, Sargunan Sockalingam, Sandra Teresa V. Navarra, Leonid Zamora, Laniyati Hamijoyo, Yasuhiro Katsumata, Masayoshi Harigai, Madelynn Chan, Sean O'Neill, Fiona Goldblatt, Chak Sing Lau, Zhan Guo Li, Alberta Hoi, Mandana Nikpour & 2 others Eric F. Morand, for the Asia Pacific Lupus Collaboration

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background
Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE.

Methods
In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares.

Findings
Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent.

Interpretation
Attainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.

Funding
UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.
Original languageEnglish
Pages (from-to)e103-e110
Number of pages8
JournalThe Lancet Rheumatology
Volume1
Issue number2
DOIs
Publication statusPublished - Oct 2019

Cite this

Golder, Vera ; Kandane-Rathnayake, Rangi ; Huq, Molla ; Louthrenoo, Worawit ; Luo, Shue Fen ; Jan Wu, Yeong Jian ; Lateef, Aisha ; Sockalingam, Sargunan ; Navarra, Sandra Teresa 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. ; for the Asia Pacific Lupus Collaboration. / Evaluation of remission definitions for systemic lupus erythematosus : a prospective cohort study. In: The Lancet Rheumatology. 2019 ; Vol. 1, No. 2. pp. e103-e110.
@article{b84eb5b0c3ad48f78eb0dce932e38326,
title = "Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study",
abstract = "BackgroundValidated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE.MethodsIn this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares.FindingsBetween May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6{\%}) to 4546 (35·8{\%}) of 12 689 visits. Spending 50{\%} or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent.InterpretationAttainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.FundingUCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.",
author = "Vera Golder and Rangi Kandane-Rathnayake and Molla Huq and Worawit Louthrenoo and Luo, {Shue Fen} and {Jan Wu}, {Yeong Jian} and Aisha Lateef and Sargunan Sockalingam and Navarra, {Sandra Teresa V.} and Leonid Zamora and Laniyati Hamijoyo and Yasuhiro Katsumata and Masayoshi Harigai and Madelynn Chan and Sean O'Neill and Fiona Goldblatt and Lau, {Chak Sing} and Li, {Zhan Guo} and Alberta Hoi and Mandana Nikpour and Morand, {Eric F.} and {for the Asia Pacific Lupus Collaboration}",
year = "2019",
month = "10",
doi = "10.1016/S2665-9913(19)30048-7",
language = "English",
volume = "1",
pages = "e103--e110",
journal = "The Lancet Rheumatology",
issn = "2665-9913",
publisher = "Elsevier",
number = "2",

}

Golder, V, Kandane-Rathnayake, R, Huq, M, Louthrenoo, W, Luo, SF, Jan Wu, YJ, Lateef, A, Sockalingam, S, Navarra, STV, Zamora, L, Hamijoyo, L, Katsumata, Y, Harigai, M, Chan, M, O'Neill, S, Goldblatt, F, Lau, CS, Li, ZG, Hoi, A, Nikpour, M, Morand, EF & for the Asia Pacific Lupus Collaboration 2019, 'Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study', The Lancet Rheumatology, vol. 1, no. 2, pp. e103-e110. https://doi.org/10.1016/S2665-9913(19)30048-7

Evaluation of remission definitions for systemic lupus erythematosus : a prospective cohort study. / Golder, Vera; Kandane-Rathnayake, Rangi; Huq, Molla; Louthrenoo, Worawit; Luo, Shue Fen; Jan Wu, Yeong Jian; Lateef, Aisha; Sockalingam, Sargunan; Navarra, Sandra Teresa 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.; for the Asia Pacific Lupus Collaboration.

In: The Lancet Rheumatology, Vol. 1, No. 2, 10.2019, p. e103-e110.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evaluation of remission definitions for systemic lupus erythematosus

T2 - a prospective cohort study

AU - Golder, Vera

AU - Kandane-Rathnayake, Rangi

AU - Huq, Molla

AU - Louthrenoo, Worawit

AU - Luo, Shue Fen

AU - Jan Wu, Yeong Jian

AU - Lateef, Aisha

AU - Sockalingam, Sargunan

AU - Navarra, Sandra Teresa V.

AU - Zamora, Leonid

AU - Hamijoyo, Laniyati

AU - Katsumata, Yasuhiro

AU - Harigai, Masayoshi

AU - Chan, Madelynn

AU - O'Neill, Sean

AU - Goldblatt, Fiona

AU - Lau, Chak Sing

AU - Li, Zhan Guo

AU - Hoi, Alberta

AU - Nikpour, Mandana

AU - Morand, Eric F.

AU - for the Asia Pacific Lupus Collaboration

PY - 2019/10

Y1 - 2019/10

N2 - BackgroundValidated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE.MethodsIn this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares.FindingsBetween May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent.InterpretationAttainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.FundingUCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

AB - BackgroundValidated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE.MethodsIn this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares.FindingsBetween May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent.InterpretationAttainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions.FundingUCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

U2 - 10.1016/S2665-9913(19)30048-7

DO - 10.1016/S2665-9913(19)30048-7

M3 - Article

VL - 1

SP - e103-e110

JO - The Lancet Rheumatology

JF - The Lancet Rheumatology

SN - 2665-9913

IS - 2

ER -