Predictive Factors of Adherence to Treatment in an International Prospective Study of Blood Hydroxychloroquine Levels in SLE Patients with Flares

Nathalie Costedoat-Chalumeau¹, Frédéric A. Houssiau², Peter M. Izmirly³, Véronique Le Guern⁴, Sandra V. Navarra⁵, Meenakshi Jolly⁶, Guillermo RUIZ-IRASTORZA⁷, Eric Hachulla⁸, Nancy Agmon-Levin⁹, Yehuda Shoenfeld¹⁰, Francesca Dall'Ara¹¹, Jill P. Buyon¹², Christophe Deligny¹³, Ricard Cervera¹⁴, Estibaliz Lazaro¹⁵, Holy Bezanahary¹⁶, Gabriel Baron¹⁷, Gaëlle Leroux¹⁸, Nathalie Morel⁴, Jean-Francois Viallard¹⁹, Christian Pineau²⁰, Lionel Galicier²¹, Ronald van Vollenhoven²², Angela Tincani²³, Hanh Nguyen²⁴, Guillaume Gondran²⁵, Noel Zahr²⁶, Jacques Pouchot²⁷, Jean Charles Piette²⁸, Michelle Petri²⁹ and David A. Isenberg³⁰, ¹Internal Medicine, Cochin University Hospital, Paris, France, ²Rheumatology, Pôle de Maladies Rhumatismales, Université catholique de Louvain, Brussels, Belgium, ³New York University School of Medicine, New York, NY, ⁴Internal Medicine Department, Cochin Hospital, “René-Descartes Paris V” University, Paris, France, ⁵Rheumatology, University of Santo Tomas Hospital, Manila, Philippines, ⁶Rush, Chicago, IL, ⁷Cruces University Hospital, Barakaldo, Spain, ⁸Internal Medicine, Lille University Hospital, Lille, France, ⁹Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Aviv, Israel, ¹⁰Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel, ¹¹University of Pavia, Pavia, Italy, ¹²Medicine, New York University School of Medicine, New York, NY, ¹³Zobda Quitman Hospital, Rheumatology and Internal Medicine, Fort de France, Martinique, ¹⁴Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain, ¹⁵Centre François Magendie, CHU de Bordeaux, Pessac, France, ¹⁶Internal Medicine, University Hospital of Limoges, Limoges, France, ¹⁷Hôpital Hôtel Dieu, Paris, France, ¹⁸Internal Medicine, Pitié-Salpêtrière University Hospital, Paris, France, ¹⁹Internal Medecine, Haut Lévèque Hospital, Bordeaux, France, ²⁰Rheumatology, MUHC, Montreal, QC, Canada, ²¹Clinical Immunology, St Louis Hospital, Paris, France, ²²Amsterdam Rheumatology Center, Amsterdam, Netherlands, ²³Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy, ²⁴Centre of Rheumatology. Medicine., University College of London Hospital, london, United Kingdom, ²⁵Internal Medicine Department, Limoges, France, ²⁶Pitié Salpêtrière, Pharmacological, Pitié Salpêtrière, Paris, France, ²⁷Internal Medicine Department, European Hospital Georges Pompidou, Paris, France, ²⁸Internal Medicine Department, University Hospital “Pitié-Salpêtrière”, “Pierre et Marie Curie Paris VI” University, Paris, France, ²⁹Rheumatology Division, Johns Hopkins University School of Medicine, Baltimore, MD, ³⁰Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Compliance, Lupus and hydroxychloroquine

Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment III: Novel and Current Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Non-adherence to treatment, a major cause of continued lupus activity and flares, may be difficult to recognize. In this international prospective study, we evaluated adherence to hydroxychloroquine (HCQ) in systemic lupus erythematosus (SLE) patients with flares (ClinicalTrials.gov: NCT01509989).

Methods:

This study included 305 SLE patients (who all met the SLICC criteria) from 19 centers in 10 countries, all of whom had been prescribed HCQ for at least 2 months and were having a disease flare according to the SELENA-SLEDAI Flare Index. Adherence to HCQ was assessed by (1) blood concentrations of HCQ and its main metabolite desethylchloroquine ([HCQ] <200ng/ml and/or undetectable [DCQ] defining severe non-adherence by dosage), (2) self-questionnaires (MASRI<80% and/or Morisky<6 defining non-adherence by questionnaires), and (3) physician’s assessments (on a VAS 0-100).

Results:

305 patients (288 women; mean age 38±12ys) met the inclusion criteria. Fifty-six patients (18.4%) were severely non-adherent by dosage (1 missing data point): 44 patients (14.5%) had [HCQ] <200ng/ml and 12 additional patients (3.9%) had an undetectable concentration of DCQ indicating a very recent resumption of treatment. Comparison between non adherent and adherent patients is summarized in table 1. These 56 non-adherent patients by dosage were younger at SLE diagnosis (28±11 vs 23±9; p=0.0025), more likely to be unemployed (46.3% vs 30.9%; p=0.03), and less likely treated with steroids (60.7% vs 79.8%; p=0.0050), whereas their exposure to immunosuppressive drugs was not different. Drug level assessment at inclusion was most often their first drug measurement (84% vs 71%, p=0.046). Their anxiety and depression scores (on the HADS questionnaire) were not different from those of the other patients. Even if their median MASRI and Morisky scores were statistically significantly lower, 24 non adherent patients (43%) would still have been defined as adherent by at least one questionnaire. Moreover, even if the median [Q1-Q3] physician’s adherence rating was statistically significantly lower in these 56 patients (75 [43-90] vs 87 [70-95], p<0.0001), their expert physicians considered that 42 patients (75%) took at least half of their treatment and even that 24 (43%) took at least 80% of their treatment.

Among the 305 patients, 121 (39.9%) were non adherent by self-questionnaires. The total non-adherence (dosage + self-questionnaires) was 47%, with only 7% of the patients being classified as non-adherent by both methods.

Conclusion:

These data show that blood HCQ and DCQ measurements objectively identify significant non-adherence in nearly 20% of SLE patients who are flaring. Non-adherence can be missed by the physician and underreported by the patient strongly suggesting the usefulness of blood assays in this setting and the value of using different methods to increase the likelihood of diagnose of non adherence.

Disclosure: N. Costedoat-Chalumeau, None; F. A. Houssiau, None; P. M. Izmirly, None; V. Le Guern, None; S. V. Navarra, None; M. Jolly, None; G. RUIZ-IRASTORZA, None; E. Hachulla, None; N. Agmon-Levin, None; Y. Shoenfeld, None; F. Dall'Ara, None; J. P. Buyon, None; C. Deligny, None; R. Cervera, None; E. Lazaro, None; H. Bezanahary, None; G. Baron, None; G. Leroux, None; N. Morel, None; J. F. Viallard, None; C. Pineau, None; L. Galicier, None; R. van Vollenhoven, None; A. Tincani, None; H. Nguyen, None; G. Gondran, None; N. Zahr, None; J. Pouchot, None; J. C. Piette, None; M. Petri, None; D. A. Isenberg, None.

To cite this abstract in AMA style:

Costedoat-Chalumeau N, Houssiau FA, Izmirly PM, Le Guern V, Navarra SV, Jolly M, RUIZ-IRASTORZA G, Hachulla E, Agmon-Levin N, Shoenfeld Y, Dall'Ara F, Buyon JP, Deligny C, Cervera R, Lazaro E, Bezanahary H, Baron G, Leroux G, Morel N, Viallard JF, Pineau C, Galicier L, van Vollenhoven R, Tincani A, Nguyen H, Gondran G, Zahr N, Pouchot J, Piette JC, Petri M, Isenberg DA. Predictive Factors of Adherence to Treatment in an International Prospective Study of Blood Hydroxychloroquine Levels in SLE Patients with Flares [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/predictive-factors-of-adherence-to-treatment-in-an-international-prospective-study-of-blood-hydroxychloroquine-levels-in-sle-patients-with-flares/. Accessed .

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