Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study

Diane Apostolopoulos, Rangi Kandane-Rathnayake, Worawit Louthrenoo, Shue Fen Luo, Yeong Jian Jan Wu, Aisha Lateef, Vera Golder, 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 NikpourEric F. Morand, for the Asia Pacific Lupus Collaboration

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Background: Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Methods: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Findings: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5–3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9–8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01–1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02–1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0–5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03–1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03–1·23], p=0·0144), and age at enrolment (1·04 [1·01–1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43–2·06], p=0·8675). Interpretation: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. Funding: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

Original languageEnglish
Pages (from-to)e24-e30
Number of pages7
JournalThe Lancet Rheumatology
Volume2
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Lupus, SLE, damage, glucocorticoids, prednisolone

Cite this

Apostolopoulos, Diane ; Kandane-Rathnayake, Rangi ; Louthrenoo, Worawit ; Luo, Shue Fen ; Jan Wu, Yeong Jian ; Lateef, Aisha ; Golder, Vera ; 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. / Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity : a multicentre cohort study. In: The Lancet Rheumatology. 2020 ; Vol. 2, No. 1. pp. e24-e30.
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title = "Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study",
abstract = "Background: Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Methods: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Findings: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5–3·0), damage accrual events were observed in 255 (14·9{\%}) patients. 1405 (82·3{\%}) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9–8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95{\%} CI 1·01–1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02–1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2{\%}) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6{\%}) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0–5·0). Accrual of irreversible organ damage occurred in 21 (13·4{\%}) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95{\%} CI 1·03–1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03–1·23], p=0·0144), and age at enrolment (1·04 [1·01–1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43–2·06], p=0·8675). Interpretation: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. Funding: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).",
keywords = "Lupus, SLE, damage, glucocorticoids, prednisolone",
author = "Diane Apostolopoulos and Rangi Kandane-Rathnayake and Worawit Louthrenoo and Luo, {Shue Fen} and {Jan Wu}, {Yeong Jian} and Aisha Lateef and Vera Golder 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 = "2020",
month = "1",
doi = "10.1016/S2665-9913(19)30105-5",
language = "English",
volume = "2",
pages = "e24--e30",
journal = "The Lancet Rheumatology",
issn = "2665-9913",
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Apostolopoulos, D, Kandane-Rathnayake, R, Louthrenoo, W, Luo, SF, Jan Wu, YJ, Lateef, A, Golder, V, 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 2020, 'Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study', The Lancet Rheumatology, vol. 2, no. 1, pp. e24-e30. https://doi.org/10.1016/S2665-9913(19)30105-5, https://doi.org/10.1016/S2665-9913(19)30105-5

Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity : a multicentre cohort study. / Apostolopoulos, Diane; Kandane-Rathnayake, Rangi; Louthrenoo, Worawit; Luo, Shue Fen; Jan Wu, Yeong Jian; Lateef, Aisha; Golder, Vera; 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. 2, No. 1, 01.2020, p. e24-e30.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity

T2 - a multicentre cohort study

AU - Apostolopoulos, Diane

AU - Kandane-Rathnayake, Rangi

AU - Louthrenoo, Worawit

AU - Luo, Shue Fen

AU - Jan Wu, Yeong Jian

AU - Lateef, Aisha

AU - Golder, Vera

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 - 2020/1

Y1 - 2020/1

N2 - Background: Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Methods: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Findings: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5–3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9–8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01–1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02–1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0–5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03–1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03–1·23], p=0·0144), and age at enrolment (1·04 [1·01–1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43–2·06], p=0·8675). Interpretation: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. Funding: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

AB - Background: Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Methods: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Findings: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5–3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9–8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01–1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02–1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0–5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03–1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03–1·23], p=0·0144), and age at enrolment (1·04 [1·01–1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43–2·06], p=0·8675). Interpretation: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. Funding: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

KW - Lupus, SLE, damage, glucocorticoids, prednisolone

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