Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

Manuel Francisco Ugarte-Gil; John Hanly; Murray Urowitz; Caroline Gordon; Sang Cheol Bae; Juanita Romero-Diaz; Jorge Sanchez-Guerrero; Sasha Bernatsky; Ann Elaine Clarke; Daniel J. Wallace; David Alan Isenberg; Anisur Rahman; Joan T. Merrill; Paul R. Fortin; Dafna D. Gladman; Ian N. Bruce; Michelle Petri; Ellen M. Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jönsen; Ronald F. Van Vollenhoven; Cynthia Aranow; Meggan MacKay; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; Ken Kalunian; Søren Jacobsen; Christine Peschken; Diane L. Kamen; Anca Askanase; Bernardo A. Pons-Estel; Graciela S. Alarcón

doi:10.1136/ard-2022-222487

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

Manuel Francisco Ugarte-Gil, John Hanly, Murray Urowitz, Caroline Gordon, Sang Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Ann Elaine Clarke, Daniel J. Wallace, David Alan Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N. Bruce, Michelle Petri, Ellen M. Ginzler, Mary Anne Dooley, Rosalind Ramsey-GoldmanSusan Manzi, Andreas Jönsen, Ronald F. Van Vollenhoven, Cynthia Aranow, Meggan MacKay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Ken Kalunian, Søren Jacobsen, Christine Peschken, Diane L. Kamen, Anca Askanase, Bernardo A. Pons-Estel, Graciela S. Alarcón

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Objective To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. Methods Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. Results There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). Conclusions Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

Original language	English
Pages (from-to)	1541-1548
Number of pages	8
Journal	Annals of the Rheumatic Diseases
Volume	81
Issue number	11
DOIs	https://doi.org/10.1136/ard-2022-222487
State	Published - 9 Aug 2022

Bibliographical note

Funding Information:
These analyses were supported by a grant from the Universidad Científica del Sur. Other sources of funding supported activities at individual Systemic Lupus International Collaborating Clinics sites: CG is supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. The views expressed are those of the authors(s) and not necessarily those of the NHS, the NIHR or the Department of Health. S-CB’s work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). AEC holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary. The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. PRF holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval. DAI and AR are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. INB is a National Institute for Health Research (NIHR) senior investigator and is supported by Arthritis Research UK, the NIHR Manchester Biomedical Centre and the NIHR/Wellcome Trust Manchester Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The Hopkins Lupus Cohort is supported by NIH (grant AR43727 and 69572). RR-G’s work was supported by NIH (grants 5UL1TR001422-02, formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464, formerly P60-AR-48098). MAD’s work was supported by NIH grant RR00046. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A3865) and the Novo Nordisk Foundation (A05990). SL’s work was supported, in part, by the Centers for Disease Control and Prevention (grant U01DP005119).

Funding Information:
All the following relationships are outside the submitted work. MF-UG: research support from Janssen and Pfizer. CG: consulting fees from the AbbVie, Amgen, AstraZeneca, Centers for Disease Control, Morton Grove Pharmaceutical (MGP), Sanofi and UCB. AEC: consulting fees from AstraZeneca, Bristol Myers Squibb, Exagen Diagnostics and GlaxoSmithKline. DAI: consulting fees from Amgen, Merck Serono, AstraZeneca and Eli Lilly (the honoraria are passed onto a local arthritis charity). AR: consulting fees from Lilly. PRF: participation on advisory boards from AbbVie, AstraZeneca and Lilly. MAK: consulting fees from GSK. MI: consulting fees from AbbVie, UCB, Novartis, Janssen and Lilly.

Funding Information:
These analyses were supported by a grant from the Universidad Científica del Sur. Other sources of funding supported activities at individual Systemic Lupus International Collaborating Clinics sites: CG is supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. The views expressed are those of the authors(s) and not necessarily those of the NHS, the NIHR or the Department of Health. S-CB’s work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). AEC holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary. The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. PRF holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Universite Laval. DAI and AR are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. INB is a National Institute for Health Research (NIHR) senior investigator and is supported by Arthritis Research UK, the NIHR Manchester Biomedical Centre and the NIHR/Wellcome Trust Manchester Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The Hopkins Lupus Cohort is supported by NIH (grant AR43727 and 69572). RR-G’s work was supported by NIH (grants 5UL1TR001422-02, formerly 8UL1TR000150 and UL-1RR- 025741, K24-AR- 02318, and P60AR064464, formerly P60-AR- 48098). MAD’s work was supported by NIH grant RR00046. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A3865) and the Novo Nordisk Foundation (A05990). SL’s work was supported, in part, by the Centers for Disease Control and Prevention (grant U01DP005119)

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© 2022 BMJ Publishing Group. All rights reserved.

Keywords

epidemiology
outcome assessment, health care
systemic lupus erythematosus

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10.1136/ard-2022-222487

Cite this

Ugarte-Gil, M. F., Hanly, J., Urowitz, M., Gordon, C., Bae, S. C., Romero-Diaz, J., Sanchez-Guerrero, J., Bernatsky, S., Clarke, A. E., Wallace, D. J., Isenberg, D. A., Rahman, A., Merrill, J. T., Fortin, P. R., Gladman, D. D., Bruce, I. N., Petri, M., Ginzler, E. M., Dooley, M. A., ... Alarcón, G. S. (2022). Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Annals of the Rheumatic Diseases, 81(11), 1541-1548. https://doi.org/10.1136/ard-2022-222487

@article{578128b0a695478492a5470726b521fa,

title = "Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort",

abstract = "Objective To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. Methods Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. Results There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). Conclusions Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.",

keywords = "epidemiology, outcome assessment, health care, systemic lupus erythematosus",

author = "Ugarte-Gil, {Manuel Francisco} and John Hanly and Murray Urowitz and Caroline Gordon and Bae, {Sang Cheol} and Juanita Romero-Diaz and Jorge Sanchez-Guerrero and Sasha Bernatsky and Clarke, {Ann Elaine} and Wallace, {Daniel J.} and Isenberg, {David Alan} and Anisur Rahman and Merrill, {Joan T.} and Fortin, {Paul R.} and Gladman, {Dafna D.} and Bruce, {Ian N.} and Michelle Petri and Ginzler, {Ellen M.} and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and {Van Vollenhoven}, {Ronald F.} and Cynthia Aranow and Meggan MacKay and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and Ken Kalunian and S{\o}ren Jacobsen and Christine Peschken and Kamen, {Diane L.} and Anca Askanase and Pons-Estel, {Bernardo A.} and Alarc{\'o}n, {Graciela S.}",

year = "2022",

month = aug,

day = "9",

doi = "10.1136/ard-2022-222487",

language = "Ingl{\'e}s",

volume = "81",

pages = "1541--1548",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "11",

}

Ugarte-Gil, MF, Hanly, J, Urowitz, M, Gordon, C, Bae, SC, Romero-Diaz, J, Sanchez-Guerrero, J, Bernatsky, S, Clarke, AE, Wallace, DJ, Isenberg, DA, Rahman, A, Merrill, JT, Fortin, PR, Gladman, DD, Bruce, IN, Petri, M, Ginzler, EM, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Van Vollenhoven, RF, Aranow, C, MacKay, M, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, K, Jacobsen, S, Peschken, C, Kamen, DL, Askanase, A, Pons-Estel, BA & Alarcón, GS 2022, 'Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort', Annals of the Rheumatic Diseases, vol. 81, no. 11, pp. 1541-1548. https://doi.org/10.1136/ard-2022-222487

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus : results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. / Ugarte-Gil, Manuel Francisco; Hanly, John; Urowitz, Murray et al.

In: Annals of the Rheumatic Diseases, Vol. 81, No. 11, 09.08.2022, p. 1541-1548.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus

T2 - results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

AU - Ugarte-Gil, Manuel Francisco

AU - Hanly, John

AU - Urowitz, Murray

AU - Gordon, Caroline

AU - Bae, Sang Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Bernatsky, Sasha

AU - Clarke, Ann Elaine

AU - Wallace, Daniel J.

AU - Isenberg, David Alan

AU - Rahman, Anisur

AU - Merrill, Joan T.

AU - Fortin, Paul R.

AU - Gladman, Dafna D.

AU - Bruce, Ian N.

AU - Petri, Michelle

AU - Ginzler, Ellen M.

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Van Vollenhoven, Ronald F.

AU - Aranow, Cynthia

AU - MacKay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, Ken

AU - Jacobsen, Søren

AU - Peschken, Christine

AU - Kamen, Diane L.

AU - Askanase, Anca

AU - Pons-Estel, Bernardo A.

AU - Alarcón, Graciela S.

PY - 2022/8/9

Y1 - 2022/8/9

N2 - Objective To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. Methods Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. Results There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). Conclusions Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

AB - Objective To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. Methods Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. Results There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). Conclusions Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

KW - epidemiology

KW - outcome assessment, health care

KW - systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=85136542044&partnerID=8YFLogxK

U2 - 10.1136/ard-2022-222487

DO - 10.1136/ard-2022-222487

M3 - Artículo

C2 - 35944946

AN - SCOPUS:85136542044

SN - 0003-4967

VL - 81

SP - 1541

EP - 1548

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 11

ER -

Ugarte-Gil MF, Hanly J, Urowitz M, Gordon C, Bae SC, Romero-Diaz J et al. Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Annals of the Rheumatic Diseases. 2022 Aug 9;81(11):1541-1548. doi: 10.1136/ard-2022-222487

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

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