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LO-024 Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC inception cohort
  1. Yann Nguyen1,2,
  2. Benoît Blanchet3,
  3. Murray B Urowitz4,
  4. John G Hanly5,
  5. Caroline Gordon6,
  6. Sang-Cheol Bae7,
  7. Juanita Romero-Diaz8,
  8. Jorge Sanchez-Guerrero9,
  9. Ann E Clarke10,
  10. Sasha Bernatsky11,
  11. Daniel J Wallace12,
  12. David A Isenberg13,
  13. Anisur Rahman13,
  14. Joan T Merrill14,
  15. Paul R Fortin15,
  16. Dafna D Gladman16,
  17. Ian N Bruce17,
  18. Michelle Petri18,
  19. Ellen M Ginzler19,
  20. Mary Anne Dooley20,
  21. Rosalind Ramsey-Goldman21,
  22. Susan Manzi22,
  23. Andreas Jönsen23,
  24. Graciela S Alarcón24,
  25. Ronald FVan Vollenhoven25,
  26. Cynthia Aranow26,
  27. Véronique Le Guern1,
  28. Meggan Mackay26,
  29. Guillermo Ruiz-Irastorza27,
  30. Sam Lin28,
  31. Murat Inanc29,
  32. Kenneth C Kalunian30,
  33. Søren Jacobsen31,
  34. Christine A Peschken32,
  35. Diane L Kamen33,
  36. Anca Askanase34,
  37. Jill Buyon35 and
  38. Nathalie Costedoat-Chalumeau1,2
  1. 1National Referral Centre for Rare Autoimmune and Systemic Diseases, Department of Internal Medicine, AP-HP.Centre – Université Paris Cité – Cochin Hospital, France
  2. 2Unité Inserm 1153, Centre de Recherche en Epidémiologie et Statistiques (CRESS), Université Paris Cité, France
  3. 3Biologie du médicament-Toxicologie, AP-HP Centre – Hôpital Cochin, Université Paris Cité, France
  4. 4Lupus Program, Centre for Prognosis Studies in The Rheumatic Disease and Schroeder Arthritis Institu, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Canada
  5. 5Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada, Canada
  6. 6Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK, UK
  7. 7Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology, Republic of Korea
  8. 8Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico
  9. 9Mount Sinai Hospital and University Health Network, University of Toronto, Canada
  10. 10Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
  11. 11Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre; Montreal, Canada
  12. 12Department of Rheumatology, Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  13. 13Centre for Rheumatology, Department of Medicine, University College London, UK
  14. 14Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  15. 15Division of Rheumatology, CHU de Québec – Université Laval, Québec City, Canada
  16. 16Lupus Program, Centre for Prognosis Studies in The Rheumatic Disease and Schroeder Arthritis Institute, Krembil Res, Canada
  17. 17NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust,, UK
  18. 18Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore,, USA
  19. 19Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
  20. 20Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
  21. 21Department of Rheumatology, Northwestern University and Feinberg School of Medicine, Chicago, USA
  22. 22Department of Rheumatology, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
  23. 23Department of Rheumatology, Lund University, Lund, Sweden
  24. 24Department of Medicine, University of Alabama at Birmingham Marnix E. Heersink School of Medicine, Birmingham, Alabama, USA
  25. 25Rheumatology and Immunology Center, University of Amsterdam, Netherlands
  26. 26Department of Rheumatology, Feinstein Institute for Medical Research, Manhasset, New York, USA
  27. 27Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Spain
  28. 28Division of Rheumatology, Emory University School of Medicine, Atlanta, USA
  29. 29Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
  30. 30Division of Rheumatology, University of California San Diego School of Medicine, La Jolla, USA
  31. 31Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  32. 32Department of Rheumatology, University of Manitoba, Winnipeg, Manitoba, Canada
  33. 33Department of Rheumatology, Medical University of South Carolina, Charleston, USA
  34. 34Department of Rheumatology, Hospital for Joint Diseases, New York University, Seligman Centre for Advanced Therapeutics, New Yor, USA
  35. 35Department of Rheumatology, New York University School of Medicine, USA


Background Hydroxychloroquine is one of the major treatment of SLE, but its effectiveness is impaired by non-adherence, reported to range from 3% to 85% in SLE patients. Our objective was to assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.

Methods The SLICC Inception Cohort is a multicenter initiative (33 centers; 11 countries). Serum of patients taking HCQ for at least 3 months, sampled at enrolment or during the first-year follow-up visit, were analyzed. Severe non-adherence was defined by a serum HCQ level <106 ng/ml or <53 ng/ml, for daily HCQ doses of 400 or 200 mg/d, respectively. Association with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) was studied with logistic regression, and association with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality were studied with separate Cox proportional hazard models.

Results Of 1849 cohort subjects, 660 patients (88% women) were included. Median [interquartile range] serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No factors were clearly associated with severe non-adherence. Severe non-adherence was independently associated with flare (OR 3.38; 95% CI 1.80–6.42) and of an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (HR 5.41; 95% CI 1.43–20.39).

Conclusions Severe non-adherence was independently associated with the risk of an SLE flare in the following year, with early damage and 5-year mortality. Our results suggest the benefits of testing of detecting severe non-adherence and dedicating more resources and more time to these patients, to improve their long-term prognosis.

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