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

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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 languageEnglish
Article number222487
JournalAnnals of the Rheumatic Diseases
DOIs
StateAccepted/In press - 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)

Publisher Copyright:
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords

  • Epidemiology
  • Health care
  • Outcome assessment
  • Systemic lupus erythematosus

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