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S15.2 Severe non-adherence to hydroxychloroquine is associated with flares, early damage, and mortality in systemic lupus erythematosus: data from 660 patients from the slicc inception cohort
  1. Y Nguyen1,
  2. B Blanchet2,
  3. MB Urowitz3,
  4. JG Hanly4,
  5. C Gordon5,
  6. S Bae6,
  7. J Romero-Dia7,
  8. J Sanchez-Guerrero8,
  9. AE Clarke9,
  10. S Bernatsky10,
  11. DJ Wallace11,
  12. DA Isenberg12,
  13. A Rahman12,
  14. JT Merrill13,
  15. PR Fortin14,
  16. DD Gladman3,
  17. IN Bruce15,
  18. M Petri16,
  19. EM Ginzler17,
  20. MA Dooley18,
  21. R Ramsey-Goldman19,
  22. S Manzi20,
  23. A Jönsen21,
  24. GS Alarcón22,
  25. RF Van Vollenhoven23,
  26. C Aranow24,
  27. V Le Gurn1,
  28. M Mackay25,
  29. G Ruiz-Irastorza26,
  30. S Lin27,
  31. M Inanc28,
  32. KC Kalunian29,
  33. S Jacobsen30,
  34. CA Peschken31,
  35. DL Kamen32,
  36. A Askanase33,
  37. J Buyon34 and
  38. N Costedoat-Chalumeau1
  1. 1National Referral Centre for Rare Autoimmune and Systemic Diseases, Department of Internal Medicine, Hôpital Cochin, AP-HP Centre; Université Paris Cité ~ Paris ~ France
  2. 2Biologie du médicament-Toxicologie, AP-HP Centre – Hôpital Cochin, Université Paris Cité ~ Paris ~ France
  3. 3Lupus Program, Centre for Prognosis Studies in The Rheumatic Disease and Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, University of Toronto ~ Canada
  4. 4Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University ~ Halifax ~ Canada
  5. 5Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham ~ UK
  6. 6Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology ~ Seoul ~ Korea, Republic of
  7. 7Instituto Nacional de Ciencias Médicas y Nutrición ~ Mexico City ~ Mexico
  8. 8Mount Sinai Hospital and University Health Network, University of Toronto ~ Toronto ~ Canada
  9. 9Division of Rheumatology, Cumming School of Medicine, University of Calgary ~ Canada
  10. 10Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre; ~ Montreal ~ Canada
  11. 11Cedars-Sinai/David Geffen School of Medicine at UCLA ~ Los Angeles ~ United States of America
  12. 12Centre for Rheumatology, Department of Medicine, University College London ~ UK
  13. 13Department of Clinical Pharmacology, Oklahoma Medical Research Foundation ~ Oklahoma City ~ United States of America
  14. 14Division of Rheumatology, CHU de Québec - Université Laval ~ Québec ~ Canada
  15. 15NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Greater Manchester, UK and Centre for Epidemiology Versus Arthritis, Faculty of Biology, Medicine and
  16. 16Division of Rheumatology, Johns Hopkins University School of Medicine ~ Baltimore ~ United States of America
  17. 17Department of Medicine, SUNY Downstate Medical Center, Brooklyn ~ New York ~ United States of America
  18. 18Thurston Arthritis Research Center, University of North Carolina ~ Chapel Hill ~ United States of America
  19. 19Northwestern University and Feinberg School of Medicine ~ Chicago ~ United States of America
  20. 20Allegheny Health Network, ~ Pittsburgh ~ United States of America
  21. 21Lund University ~ Lund ~ Sweden
  22. 22Department of Medicine, University of Alabama at Birmingham Marnix E. Heersink School of Medicine ~ Birmingham ~ United States of America
  23. 23University of Amsterdam, Rheumatology & Immunology Center ~ Amsterdam ~ Netherlands
  24. 24Feinstein Institute for Medical Research, ~ Manhasset ~ United States of America
  25. 25Feinstein Institute for Medical Research, Manhasset ~ New York ~ United States of America
  26. 26Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country ~ Barakaldo ~ Spain
  27. 27Emory University School of Medicine, Division of Rheumatology ~ Atlanta ~ United States of America
  28. 28Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University ~ Istanbul ~ Turkey
  29. 29University of California San Diego School of Medicine ~ La Jolla ~ United States of America
  30. 30Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital ~ Copenhagen ~ Denmark
  31. 31University of Manitoba ~ Winnipeg ~ Canada
  32. 32Medical University of South Carolina ~ Charleston ~ United States of America
  33. 33Hospital for Joint Diseases, New York University, Seligman Centre for Advanced Therapeutics ~ New York ~ United States of America
  34. 34New York University School of Medicine ~ New York ~ United States of America


Purpose The efficacy of antimalarials, especially hydroxychloroquine (HCQ), in preventing flares of systemic lupus erythematosus (SLE) is well demonstrated, but its effectiveness is impaired by non-adherence to treatment, reported to vary between 3% and 85%.

We aimed to assess the associations of baseline 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 multicentric prospective study of SLE patients from 31 centers in 11 countries. Patients were enrolled within 15 months of recognition of SLE (1997 ACR classification criteria). Serum HCQ levels of patients with HCQ prescription for at least 3 months, sampled at enrollment (or, if unavailable, during the first-year follow-up visits), were centrally measured. Severe non-adherence was defined by a serum HCQ level <106 ng/mL for a daily prescribed HCQ dose of 400 mg, and <53 ng/mL for a daily HCQ dose of 200 mg, respectively (1). SLE flare was defined by the occurrence of one of the following events within the first year following serum collection: (a) increase of at least four point in the SLEDAI-2K; (b) new start in prednisone (oral or pulse) or immunosuppressive agent; (c) a new renal involvement (active nephritis, nephrotic syndrome). Association between severe non-adherence and SLE flare was assessed with logistic regression models, further adjusted on potential confounders. Damage was assessed by the time until an increase ≥1 in the SLICC damage index (SDI), within the 5 years following HCQ measurement. Associations between severe non-adherence and either damage or mortality (from all cause) within 5 years following HCQ measurement were assessed with Cox proportional hazard models, adjusted on sex, education, and potential confounders.

Results Of 1849 cohort subjects, 660 patients (88% women) were included. Median [interquartile range] serum HCQ level was 388 ng/mL (244–566) and 48 patients (7.3%) had severe HCQ non-adherence. No factors were clearly associated with severe non-adherence. A SLE flare occurred in 191 (28.9%) patients within the first year (28 [58.3%] non-adherent patients versus 163 [26.6%] other patients). In multivariate analysis, severe nonadherence was independently associated with the risk of flare (OR= 3.32; 95% CI 1.78–6.28).

Within five years, 167 patients (25.3%) had ≥1 point increase of SDI. Severe on-adherence was associated with 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 (unadjusted HR 5.41; 95% CI 1.43–20.39).

Abstract S15.2 Figure 1

Risk of damage, defined by a ≥1-point increase in SLICC ACR damage index, according to severe non-adherence to hydroxychloroquine (n=660)

Conclusions In this large multicentric international prospective cohort, severe non-adherence was independently associated with the risk of SLE flare in the following year, with early damage, and 5-year mortality. As severe non-adherence is often unknown by the physician and since no predictive clinical or biological factors were identified, our results suggest the benefits of testing to detect severe non-adherence, to identify the patients at risk.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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