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

Author:

Ugarte-Gil Manuel FranciscoORCID,Hanly John,Urowitz MurrayORCID,Gordon Caroline,Bae Sang-CheolORCID,Romero-Diaz Juanita,Sanchez-Guerrero Jorge,Bernatsky SashaORCID,Clarke Ann Elaine,Wallace Daniel JORCID,Isenberg David AlanORCID,Rahman AnisurORCID,Merrill Joan T,Fortin Paul RORCID,Gladman Dafna DORCID,Bruce Ian N,Petri MichelleORCID,Ginzler Ellen M,Dooley Mary Anne,Ramsey-Goldman Rosalind,Manzi Susan,Jönsen Andreas,van Vollenhoven Ronald FORCID,Aranow CynthiaORCID,Mackay Meggan,Ruiz-Irastorza GuillermoORCID,Lim Sam,Inanc MuratORCID,Kalunian Ken,Jacobsen Søren,Peschken Christine,Kamen Diane L,Askanase Anca,Pons-Estel Bernardo A,Alarcón Graciela SORCID

Abstract

ObjectiveTo determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual.MethodsPatients 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.ResultsThere 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)).ConclusionsRemission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

Funder

the Department of Education, Universities and Research of the Basque Government

National Institutes of Health

Sandwell and West Birmingham Hospitals NHS Trust

National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility

Centers for Disease Control and Prevention

LUPUS UK

Singer Family Fund for Lupus Research

National Institute for Health Research University College London Hospitals Biomedical Research Centre

Canada Research Chair on Systemic Autoimmune Rheumatic Diseases

Universidad Cientifica del Sur

National Research Foundation of Korea

The Arthritis Society Chair in Rheumatic Diseases

NIHR/Wellcome Trust Manchester Clinical Research Facility

Danish Rheumatism Association

Arthritis Research UK

Novo Nordisk Foundation

NIHR Manchester Biomedical Centre

Publisher

BMJ

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology

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