Hydroxychloroquine blood levels in stable lupus nephritis under low dose (2-3 mg/kg/day): 12-month prospective randomized controlled trial

Author(s)

Zanetti, Caio B. ^[1] ; Pedrosa, Tatiana ^[1] ; Kupa, Leonard de V. K. ^{[1, 2]} ; Aikawa, Nadia E. ^{[1, 3]} ; Borba, Eduardo F. ^[1] ; Vendramini, Margarete B. G. ^[1] ; Silva, Clovis A. ^[3] ; Pasoto, Sandra G. ^[1] ; Bonfa, Eloisa ^[1]

Affiliation

^[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Rheumatol Div, Av Dr 455, 3 Andar, Sala 3192, BR-01246903 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Fac Med, Div Cent Lab, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Pediat Rheumatol Unit, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CLINICAL RHEUMATOLOGY; v. 40, n. 7 JAN 2021.
• Web of Science Citations: 0

Abstract

Introduction The American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that prescribed 2016-AAO dose provided adequate HCQ levels for most lupus nephritis (LN) patients, with low flare risk. However, the minimum HCQ dose required to keep adequate levels is unknown. Objectives To evaluate if a further reduction in 2016-AAO dose (2-3 mg/kg/day) would sustain 12-month HCQ levels in LN patients with stable inactive disease. Methods Seventy-three stable LN patients under prescribed full HCQ 2016-AAO dose for >= 6 months and adequate baseline HCQ levels (>= 613.5 ng/mL) were divided in two groups: reduced 2016-AAO dose (2-3 mg/kg/day), n = 32, and full 2016-AAO dose (5 mg/kg/day), n = 41. All patients were assessed at baseline, 3, 6, and 12 months. HCQ levels were measured by liquid chromatography-tandem mass spectrometry. Flare was defined as augment >= 3 in SLE Disease Activity Index-2000 and/or change in treatment. Rigorous clinical/laboratorial surveillance was performed. Results Prospective evaluation revealed for reduced 2016-AAO dose group a decrease of HCQ levels from baseline to 3 months (1,404.9 +/- 492.0 vs. 731.6 +/- 385.0 ng/mL, p < 0.01), and sustained levels at 6 months (p = 0.273) and 12 months (p = 0.091) compared to 3 months. For the full 2016-AAO dose group, a decrease occurred only from baseline to 12 months (1343.5 +/- 521.5 vs. 991.6 +/- 576.3 ng/mL, p < 0.001). Frequencies of patients with inadequate levels at 6 months was higher in reduced 2016-AAO group than full 2016-AAO dose (59% vs. 24%, p = 0.005), as well as at 12 months (66% vs. 32%, p = 0.002). Six-month and 12-month flare frequencies were comparable for both groups (p > 0.05). Conclusions Prescribed HCQ low-dose regimen (2-3 mg/kg/day) does not sustain, for most patients, 6- and 12-month adequate HCQ levels. Full 2016-AAO dose maintained HCQ levels way above this limit. Trail registration: NCT03122431, registered on April 20, 2017 (AU)

• 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: 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: 17/03983-6 - Liquid chromatography coupled to mass spectrometry (2015/03756-4)
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Multi-user Equipment Program