The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Author(s)

Pedrosa, Tatiana ^[1] ; Kanda Kupa, Leonard de Vinci ^{[1, 2]} ; Pasoto, Sandra Gofinet ^[1] ; Aikawa, Nadia Emi ^{[1, 3]} ; Borba, Eduardo Ferreira ^[1] ; Duarte, Nilo J. C. ^[2] ; Leon, Elaine Pires ^[1] ; Silva, Clovis Artur ^[3] ; Bonfa, Eloisa ^[1]

Affiliation

^[1] Univ Sao Paulo, Rheumatol Div, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Div Cent Lab, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Pediat Rheumatol Unit, Sao Paulo - Brazil

• Document type: Journal article
• Source: Lupus; v. 30, n. 4, p. 554-559, APR 2021.
• Web of Science Citations: 0

Abstract

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI >= 30kg/m(2). Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) {[}4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 +/- 548.6 vs. 1208 +/- 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients {[}4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 +/- 457.3 vs. 1189 +/- 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov \#NCT0312243. (AU)

• FAPESP's process: 19/17272-0 - Relevance of monitoring blood levels compared to salivar levels of drugs used in rheumatic autoimmune diseases: adherence and understanding the possible underlying mechanisms involved in effectiveness and in adverse effects
• Grantee: Leonard de Vinci Kanda Kupa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/14352-7 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Tatiana Do Nascimento Pedrosa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/03983-6 - Liquid chromatography coupled to mass spectrometry (2015/03756-4)
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Multi-user Equipment Program