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THU0304 Adherence To Hydroxychloroquine as Assessed by Measurements of Drug and Metabolite Blood Levels in An International Prospective Study of Sle Patients in Flare
  1. N. Costedoat-Chalumeau1,
  2. F. Houssiau2,
  3. P. Izmirly3,
  4. V. Le Guern1,
  5. S. Navarra4,
  6. M. Jolly5,
  7. G. Ruiz-Irastorza6,
  8. E. Hachulla7,
  9. N. Agmon-Levin8,
  10. Y. Shoenfeld8,
  11. F. Dall'Ara9,
  12. J. Buyon3,
  13. C. Deligny10,
  14. R. Cervera11,
  15. E. Lazaro12,
  16. H. Bezanahary13,
  17. G. Leroux14,
  18. N. Morel1,
  19. J.-F. Viallard12,
  20. C. Pineau15,
  21. L. Galicier16,
  22. R. Van Vollenhoven17,
  23. A. Tincani9,
  24. H. Nguyen18,
  25. G. Gondran13,
  26. N. Zahr19,
  27. J. Pouchot20,
  28. J.-C. Piette14,
  29. M. Petri21,
  30. D. Isenberg18
  1. 1Cochin Hospital, Internal Medicine, Paris, France
  2. 2Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Rheumatology and Internal Medicine, Bruxelles, Belgium
  3. 3NYU Langone Medical Center, Center for Musculoskeletal Care, New York, United States
  4. 4University of Santo Tomas Hospital, Rheumatology, Manila, Philippines
  5. 5Rush University Medical Center, Rush Lupus Clinic, Chicago, United States
  6. 6Hospital Universitario Cruces, Internal Medicine, Barakaldo, Spain
  7. 7Claude Huriez Hospital, Internal Medicine, Lille, France
  8. 8Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Israel
  9. 9Spedali Civili e Università degli Studi di Brescia, Rheumatology and Internal Medicine, Brescia, Italy
  10. 10Pierre-Zobda-Quitman Hospital, Internal Medicine, Martinique, France
  11. 11Hospital Clínic de Barcelona, Autoimmune Diseases, Barcelona, Spain
  12. 12Haut Lévêque Hospital, Internal Medicine, Pessac
  13. 13Dupuytren Hospital, Internal Medicine, Limoges
  14. 14Pitié-Salpêtrière Hospital, Internal Medicine, Paris, France
  15. 15Montreal General Hospital, Lupus Clinic, Montreal, Canada
  16. 16St Louis Hospital, Clinical Immunology, Paris, France
  17. 17The Karolinska University Hospital, Medicine, Unit for Clinical Research Therapy, Inflammatory Diseases, Stockholm, Sweden
  18. 18University College London, Centre for Rheumatology, London, United Kingdom
  19. 19Hopital Pitié-Salpêtrière, Pharmacology, Paris
  20. 20European Georges Pompidou Hospital, Internal Medicine, Paris, France
  21. 21Johns Hopkins Center, Rheumatology, Baltimore, United States

Abstract

Background Non-adherence to treatment, a major cause of continued lupus activity and flares, may be difficult to recognize.

Objectives In this international prospective study, we evaluated adherence to hydroxychloroquine (HCQ) in SLE patients with flares (NCT01509989).

Methods This study included 305 SLE patients (SLICC criteria) from 10 countries, all of whom had been prescribed HCQ for ≥2 months and were having a disease flare (SELENA-SLEDAI Flare Index). Adherence to HCQ was assessed by self-questionnaires (MASRI, Morisky), physician's assessment (VAS 0–100), and blood concentrations of HCQ and its main metabolite desethylchloroquine ([HCQ] and [DCQ]). Non-adherence was defined by MASRI <80%, Morisky<6, [HCQ] <200ng/ml and/or undetectable [DCQ].

Results 305 patients (288 women; mean age 38 ± 12ys) met the inclusion criteria. The median SLE duration was 11ys [range 1–46]; 108 patients (35%) had a history of lupus nephritis.

At enrollment, the median SELENA-SLEDAI score was 8 [2–30] and the flare was considered severe in 43%. The HCQ dosage was 400mg/d in 72%, 200mg/d in 15%, or another dosage in 13%. The median [HCQ] was 718ng/ml [0–4345]. In addition, steroids were prescribed in 76%, and immunosuppressives in 46%.

Severe non-adherence defined by [HCQ] <200ng/ml was found in 44 patients (14.4%). 12 additional patients with very low median [HCQ] of 235ng/ml [210–343] had an undetectable [DCQ] indicating a very recent resumption of treatment. Thus, 56 patients (18.4%) were objectively defined as severely non-adherent. Table 1 shows that the treating physician believed that 75% of these non-adherent patients were taking at least 50% of their prescribed HCQ dose, strongly suggesting that doctors were often unaware of non-adherence. The median VAS evaluating the adherence from the doctor's point of view was 75 [0–98] in objectively non-adherent patients vs 87 [0–100] in other patients. The doctor's opinion, therefore, was poorly informative.

Good adherence to treatment with HCQ (MASRI ≥80%) was self-reported by 77% of the patients, including by 43% of those objectively severely non-adherent.

On the other hand, the investigators felt that only 12% of patients took less than 50% of HCQ, with severe non-adherence confirmed in 39%. Conversely, while intake was estimated at ≥75% (65%), 15% of these patients were objectively severely non-adherent.

Non-adherent patients defined by self-questionnaires (MASRI<80% or Morisky <6) and/or drug blood levels, represented 47% of this cohort.

Conclusions These data demonstrate that blood HCQ and DCQ measurements objectively identify significant non-adherence to HCQ in nearly 20% of SLE patients. Non-adherence was often unrecognized by the doctor, suggesting usefulness of blood assays to more accurately determine adherence.

Disclosure of Interest None declared

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