ESPN 53rd Annual Meeting

ESPN 2021


 
Evaluation of Hydroxychloroquine Blood Concentrations and Effects in Childhood-Onset Systemic Lupus Erythematosus
MARGAUX BOISTAULT 1 SAIK URIEN 1 CHRISTIAN FUNCK-BRENTANO 1 HéLèNE VANTOMME 1 NICOLAS GARCELON 1 ISABELLE MELKI 1 BRIGITTE BADER-MEUNIER 1 NOEL ZAHR 2 OLIVIA BOYER 1

1- AP-HP. UNIVERSITé DE PARIS, NECKER HOSPITAL, DEPARTMENT OF PEDIATRIC NEPHROLOGY, REFERENCE CENTER FOR IDIOPATHIC NEPHROTIC SYNDROME IN CHILDREN AND ADULTS, IMAGINE INSTITUTE, LABORATORY OF HEREDITARY KIDNEY DISEASES, INSERM U1163, PARIS, FRANCE
2- AP-HP. SORBONNE UNIVERSITé, PITIé-SALPêTRIèRE HOSPITAL, DEPARTMENT OF PHARMACOLOGY AND CLINICAL INVESTIGATION CENTER; INSERM, CIC-1901 AND UMR ICAN 1166, SORBONNE UNIVERSITé, FACULTY OF MEDICINE; SORBONNE UNIVERSITé, FACULTY OF MEDICINE, F-75013 PARIS, FRANCE
 
Abstract:

Introduction : Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-effect relationships in children remains unknown. Therefore, this study aimed to investigate the pharmacokinetics of HCQ and possible concentration-effect relationships. 

Methods : HCQ blood concentrations and effects were obtained on a daily basis during clinical routine at different occasions during the treatment. cSLE flares were defined using the SLE Disease Activity Index (SLEDAI); flare was denoted by a SLEDAI score > 6.  Blood concentration was measured using high-performance liquid chromatography with fluorometric detection. Statistical analysis was performed  using a non linear mixed-effect approach via Monolix. 

Results : A total of 168 blood samples were obtained from 55 pediatric patients. HCQ apparent blood clearance (CL/F) was dependent on patients’ body weight and platelet count. Patients with active cSLE had a lower mean blood HCQ concentration compared with inactive cSLE patients (536 ± 294 vs 758 ± 490 ng/mL, p = 5 x 10-6). Among patients with HCQ blood concentration ≥ 750 ng/mL, 87.6% had inactive cSLE. Moreover, HCQ blood concentration was a significant predictor of disease status. 

Conclusion : We developed the first HCQ blood concentration-effect relationship for cSLE in terms of  active or non-active disease status. To confirm these results, a prospective analysis is necessary.