Assessment of hydroxychloroquine blood levels in patients with Sjögren\'s disease: medication adherence and clinical correlations

Author(s)

Lorena Elizabeth Betancourt Villamarin

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2024-02-21

Examining board members

Sandra Gofinet Pasoto; Eduardo Ferreira Borba Neto; Edgard Torres dos Reis Neto; Carla Gonçalves Schahin Saad

• Advisor: Sandra Gofinet Pasoto

Abstract

Introduction: Hydroxychloroquine (HCQ) is a potential therapeutic option for Sjögren\'s disease (SjD). Nevertheless, there are no studies assessing drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. In addition, the possible associations of HCQ blood levels with glandular and extraglandular disease parameters were poorly evaluated. Objectives: To assess medication adherence to HCQ in SjD through the concomitant determination of drug blood levels and clinical instruments, as well as to analyze the possible associations between HCQ blood levels and the various glandular and extraglandular disease parameters. Methods: This observational cross-sectional study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least three months before study inclusion. HCQ blood levels were determined by high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS). Adherence to HCQ was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory (XI), Ocular Surface Disease Index (OSDI), EULAR (European League Against Rheumatism) Sjögrens Syndrome Patient Reported Index (ESSPRI), EULAR Sjögrens Syndrome Disease Activity Index (ESSDAI), Schirmers I test and unstimulated/stimulated salivary flow rates. Results: HCQ blood levels were 775.3 (minimum 25.0 maximum 2,568.6) ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200 ng/mL (non-adherent group); 11 (14.9%), 200 499 ng/mL (group with sub-therapeutic levels); and 52 (70.2%), 500 ng/mL (adherent group). PR classified incorrectly all patients in the non-adherent/sub-therapeutic levels groups and 2/52 (3.9%) adherent patients. Using MAT, the overall misclassification was 24/52 (46.2%) in the adherent group; and 9/11 (81.8%) patients in the non-adherent group and 7/11 (63.6%) in the group with sub-therapeutic levels were correctly identified. The sensitivity and specificity of MAT to identify patients in the non-adherent/sub- therapeutic levels groups were 72.7% and 53.9%, respectively. The three groups were similar regarding glandular and extraglandular disease parameters (P > 0.05). Conclusions: The evaluation of HCQ blood levels is a promising tool for appraising drug adherence in SjD. This is especially important as one-third of patients presented non-adherence and sub-therapeutic levels, and neither PR nor MAT consistently identified these patients (AU)

• FAPESP's process: 20/09367-8 - Analysis of blood hydroxychlorochine levels in patients with primary Sjogren Syndrome and possible correlation with the disease activity
• Grantee: Lorena Elizabeth Betancourt Villamarín
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)