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Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis

2021; SAGE Publishing; Volume: 31; Issue: 1 Linguagem: Inglês

10.1177/09612033211062515

1477-0962

Verena Andrade Balbi, Clóvis A. Silva, Tatiana do Nascimento Pedrosa, Rosa Maria Rodrigues Pereira, Lúcia Maria Arruda Campos, Elaine Pires Leon, Nilo José Coêlho Duarte, Valdemir Melechco Carvalho, Sandra Gofinet Pasoto, Débora Cordeiro do Rosário, Leticia Kolachinski Brandao, Hermine I. Brunner, Eloísa Bonfá, Nádia Emi Aikawa,

Pharmacological Effects of Natural Compounds

Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN).Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry.There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013).We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.