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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
  1. Manuel Francisco Ugarte-Gil1,2,
  2. John Hanly3,
  3. Murray Urowitz4,
  4. Caroline Gordon5,
  5. Sang-Cheol Bae6,7,
  6. Juanita Romero-Diaz8,
  7. Jorge Sanchez-Guerrero8,9,
  8. Sasha Bernatsky10,
  9. Ann Elaine Clarke11,
  10. Daniel J Wallace12,
  11. David Alan Isenberg13,
  12. Anisur Rahman13,
  13. Joan T Merrill14,
  14. Paul R Fortin15,
  15. Dafna D Gladman4,
  16. Ian N Bruce16,
  17. Michelle Petri17,
  18. Ellen M Ginzler18,
  19. Mary Anne Dooley19,
  20. Rosalind Ramsey-Goldman20,
  21. Susan Manzi21,
  22. Andreas Jönsen22,
  23. Ronald F van Vollenhoven23,
  24. Cynthia Aranow24,
  25. Meggan Mackay24,
  26. Guillermo Ruiz-Irastorza25,
  27. Sam Lim26,
  28. Murat Inanc27,
  29. Ken Kalunian28,
  30. Søren Jacobsen29,
  31. Christine Peschken30,
  32. Diane L Kamen31,
  33. Anca Askanase32,
  34. Bernardo A Pons-Estel33,
  35. Graciela S Alarcón34,35
  1. 1 Grupo Peruano de Estudio de Enfermedades Autoinmunes Sistemicas, Universidad Cientifica del Sur, Lima, Peru
  2. 2 Rheumatology, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru
  3. 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. 4 Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
  5. 5 Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  6. 6 Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
  7. 7 Hanyang University Institute for Rheumatology Research and Hanyang University Institute of Bioscience and Biotechnology, Seoul, South Korea
  8. 8 Inmunología y Reumatología, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  9. 9 Sinai Health System and University Health Network, Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada
  10. 10 Divisions of Rheumatology and Clinical Epidemiology, McGill University, Montreal, Québec, Canada
  11. 11 Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  12. 12 Cedars Sinai/David Geffen School of Medicine, UCLA, Los Angeles, California, USA
  13. 13 Medicine, University College London, London, UK
  14. 14 Department of Clinical Pathology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  15. 15 Centre ARThrite, Rheumatology, CHU de Québec - Université Laval, Quebec, Quebec, Canada
  16. 16 Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Center, University of Manchester, Manchester, UK
  17. 17 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  18. 18 Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
  19. 19 Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
  20. 20 Department of Medicine, Division of Rheumatology, Northwestern University and Feinberg School of Medicine, Chicago, Illinois, USA
  21. 21 Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
  22. 22 Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden
  23. 23 Department of Rheumatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
  24. 24 Northwell Health Manhasset, The Feinstein Institute for Medical Research, Manhasset, New York, USA
  25. 25 Autoimmune Diseases Research Unit. BioCruces Bizkaia Health Research Institute, University of the Basque Country, Balakaldo, Spain
  26. 26 School of Medicine, Division of Rheumatology, Emory University, Atlanta, Georgia, USA
  27. 27 Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey
  28. 28 School of Medicine, University of California San Diego, La Jolla, California, USA
  29. 29 Copenhagen Research Center for Autoimmune Connective Tissue Diseases, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
  30. 30 Departments of Medicine and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  31. 31 Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA
  32. 32 Columbia University Irving Medical Center, New York, New York, USA
  33. 33 Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina
  34. 34 Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  35. 35 Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru
  1. Correspondence to Manuel Francisco Ugarte-Gil, Grupo Peruano de Estudio de Enfermedades Autoinmunes Sistemicas, Universidad Científica del Sur, Miraflores, Lima, Peru; mugarte{at}


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.

  • systemic lupus erythematosus
  • outcome assessment, health care
  • epidemiology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Handling editor Josef S Smolen

  • Twitter @mugartegil

  • Contributors All authors were involved in building and maintaining the study cohort, drafting or revising this article critically for important intellectual content, and approved the final version to be published. Dr Manuel F Ugarte-Gil had full access to all relevant data from the study and takes responsibility for their integrity and the accuracy of the analyses performed.

  • Funding 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).

  • 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.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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