. 2022 Nov;81(11):1541-1548.

doi: 10.1136/ard-2022-222487. Epub 2022 Aug 9.

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^{1

2}, John Hanly³, Murray Urowitz⁴, Caroline Gordon⁵, Sang-Cheol Bae^{6

7}, Juanita Romero-Diaz⁸, Jorge Sanchez-Guerrero^{8

9}, Sasha Bernatsky¹⁰, Ann Elaine Clarke¹¹, Daniel J Wallace¹², David Alan Isenberg¹³, Anisur Rahman¹³, Joan T Merrill¹⁴, Paul R Fortin¹⁵, Dafna D Gladman⁴, Ian N Bruce¹⁶, Michelle Petri¹⁷, Ellen M Ginzler¹⁸, Mary Anne Dooley¹⁹, Rosalind Ramsey-Goldman²⁰, Susan Manzi²¹, Andreas Jönsen²², Ronald F van Vollenhoven²³, Cynthia Aranow²⁴, Meggan Mackay²⁴, Guillermo Ruiz-Irastorza²⁵, Sam Lim²⁶, Murat Inanc²⁷, Ken Kalunian²⁸, Søren Jacobsen²⁹, Christine Peschken³⁰, Diane L Kamen³¹, Anca Askanase³², Bernardo A Pons-Estel³³, Graciela S Alarcón^{34

35}

Affiliations

¹ Grupo Peruano de Estudio de Enfermedades Autoinmunes Sistemicas, Universidad Cientifica del Sur, Lima, Peru mugarte@cientifica.edu.pe.
² Rheumatology, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
³ Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
⁴ Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
⁵ Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
⁶ Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
⁷ Hanyang University Institute for Rheumatology Research and Hanyang University Institute of Bioscience and Biotechnology, Seoul, South Korea.
⁸ Inmunología y Reumatología, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
⁹ Sinai Health System and University Health Network, Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Divisions of Rheumatology and Clinical Epidemiology, McGill University, Montreal, Québec, Canada.
¹¹ Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹² Cedars Sinai/David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
¹³ Medicine, University College London, London, UK.
¹⁴ Department of Clinical Pathology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
¹⁵ Centre ARThrite, Rheumatology, CHU de Québec - Université Laval, Quebec, Quebec, Canada.
¹⁶ Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Center, University of Manchester, Manchester, UK.
¹⁷ Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁸ Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA.
¹⁹ Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
²⁰ Department of Medicine, Division of Rheumatology, Northwestern University and Feinberg School of Medicine, Chicago, Illinois, USA.
²¹ Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.
²² Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden.
²³ Department of Rheumatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²⁴ Northwell Health Manhasset, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
²⁵ Autoimmune Diseases Research Unit. BioCruces Bizkaia Health Research Institute, University of the Basque Country, Balakaldo, Spain.
²⁶ School of Medicine, Division of Rheumatology, Emory University, Atlanta, Georgia, USA.
²⁷ Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey.
²⁸ School of Medicine, University of California San Diego, La Jolla, California, USA.
²⁹ Copenhagen Research Center for Autoimmune Connective Tissue Diseases, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
³⁰ Departments of Medicine and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
³¹ Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
³² Columbia University Irving Medical Center, New York, New York, USA.
³³ Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina.
³⁴ Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
³⁵ Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.

PMID: 35944946
PMCID: PMC10353886
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 et al. Ann Rheum Dis. 2022 Nov.

. 2022 Nov;81(11):1541-1548.

doi: 10.1136/ard-2022-222487. Epub 2022 Aug 9.

Authors

Affiliations

¹ Grupo Peruano de Estudio de Enfermedades Autoinmunes Sistemicas, Universidad Cientifica del Sur, Lima, Peru mugarte@cientifica.edu.pe.
² Rheumatology, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru.
³ Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
⁴ Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
⁵ Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
⁶ Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
⁷ Hanyang University Institute for Rheumatology Research and Hanyang University Institute of Bioscience and Biotechnology, Seoul, South Korea.
⁸ Inmunología y Reumatología, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
⁹ Sinai Health System and University Health Network, Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Divisions of Rheumatology and Clinical Epidemiology, McGill University, Montreal, Québec, Canada.
¹¹ Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹² Cedars Sinai/David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
¹³ Medicine, University College London, London, UK.
¹⁴ Department of Clinical Pathology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
¹⁵ Centre ARThrite, Rheumatology, CHU de Québec - Université Laval, Quebec, Quebec, Canada.
¹⁶ Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Center, University of Manchester, Manchester, UK.
¹⁷ Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁸ Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA.
¹⁹ Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
²⁰ Department of Medicine, Division of Rheumatology, Northwestern University and Feinberg School of Medicine, Chicago, Illinois, USA.
²¹ Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.
²² Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden.
²³ Department of Rheumatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²⁴ Northwell Health Manhasset, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
²⁵ Autoimmune Diseases Research Unit. BioCruces Bizkaia Health Research Institute, University of the Basque Country, Balakaldo, Spain.
²⁶ School of Medicine, Division of Rheumatology, Emory University, Atlanta, Georgia, USA.
²⁷ Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey.
²⁸ School of Medicine, University of California San Diego, La Jolla, California, USA.
²⁹ Copenhagen Research Center for Autoimmune Connective Tissue Diseases, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.
³⁰ Departments of Medicine and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
³¹ Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
³² Columbia University Irving Medical Center, New York, New York, USA.
³³ Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina.
³⁴ Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
³⁵ Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.

PMID: 35944946
PMCID: PMC10353886
DOI: 10.1136/ard-2022-222487

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: 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.

Comment in

Defining the targets in SLE management: insights and unmet gaps.
Zen M, Gatto M, Doria A. Zen M, et al. Ann Rheum Dis. 2022 Nov;81(11):1483-1485. doi: 10.1136/ard-2022-222991. Epub 2022 Aug 25. Ann Rheum Dis. 2022. PMID: 36008131 No abstract available.

Cited by

Advances in Targeted Therapy for Systemic Lupus Erythematosus: Current Treatments and Novel Approaches.
Saegusa K, Tsuchida Y, Komai T, Tsuchiya H, Fujio K. Saegusa K, et al. Int J Mol Sci. 2025 Jan 23;26(3):929. doi: 10.3390/ijms26030929. Int J Mol Sci. 2025. PMID: 39940698 Free PMC article. Review.
Weaning Maintenance Therapy in Lupus Nephritis: For Whom, When, and How?
Jourde-Chiche N, Bobot M, Burtey S, Chiche L, Daugas E. Jourde-Chiche N, et al. Kidney Int Rep. 2023 May 22;8(8):1481-1488. doi: 10.1016/j.ekir.2023.05.012. eCollection 2023 Aug. Kidney Int Rep. 2023. PMID: 37547513 Free PMC article. Review.
Autologous haematopoietic stem cell transplantation for rheumatic diseases: best practice recommendations from the EBMT Practice Harmonization and Guidelines Committee.
Alexander T, Roldan E, Del Papa N, Farge D, Henes J, Marjanovic Z, Puyade M, Snowden JA, Spierings J, de Vries-Bouwstra JK, Onida F, Ruggeri A, Sánchez-Ortega I, Burt R, Cervera R, Doria A, Moore J, Oliveira MC, Pugnet G, Rimar D, Schmalzing M, Yakoub-Agha I, Greco R. Alexander T, et al. Bone Marrow Transplant. 2025 Aug 20. doi: 10.1038/s41409-025-02695-y. Online ahead of print. Bone Marrow Transplant. 2025. PMID: 40830237
Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study-Joint and Skin (BeRLiSS-JS).
Zen M, Gatto M, Depascale R, Regola F, Fredi M, Andreoli L, Franceschini F, Urban ML, Emmi G, Ceccarelli F, Conti F, Bortoluzzi A, Govoni M, Tani C, Mosca M, Ubiali T, Gerosa M, Bozzolo EP, Canti V, Cardinaletti P, Gabrielli A, Tanti G, Gremese E, De Marchi G, De Vita S, Fasano S, Ciccia F, Pazzola G, Salvarani C, Negrini S, Di Matteo A, De Angelis R, Orsolini G, Rossini M, Faggioli P, Laria A, Piga M, Cauli A, Scarpato S, Rossi FW, De Paulis A, Brunetta E, Ceribelli A, Selmi C, Prete M, Racanelli V, Vacca A, Bartoloni E, Gerli R, Zanatta E, Larosa M, Saccon F, Doria A, Iaccarino L. Zen M, et al. J Pers Med. 2023 Apr 20;13(4):691. doi: 10.3390/jpm13040691. J Pers Med. 2023. PMID: 37109077 Free PMC article.
Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus.
Recio-Barbero M, Cabezas-Garduño J, Varona J, Ruiz-Irastorza G, Horrillo I, Meana JJ, Santos-Zorrozúa B, Segarra R. Recio-Barbero M, et al. J Clin Med. 2024 Sep 13;13(18):5423. doi: 10.3390/jcm13185423. J Clin Med. 2024. PMID: 39336910 Free PMC article.

See all "Cited by" articles

References

1. van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrom K, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 2014;73(6):958–67. - PubMed
1. Ugarte-Gil MF, Mendoza-Pinto C, Reategui-Sokolova C, Pons-Estel GJ, van Vollenhoven RF, Bertsias G, et al. Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review. Lupus Sci Med 2021;8(1): e000542. - PMC - PubMed
1. van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci Med 2021;8(1):e000538. - PMC - PubMed
1. Polachek A, Gladman DD, Su J, Urowitz MB. Defining Low Disease Activity in Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken) 2017;69(7):997–1003. - PubMed
1. Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis 2016;75(9):1615–21. - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Abstract

Conflict of interest statement

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical