Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis

Author(s):Show less -

Pedrosa, Tatiana N. ^[1] ; Pasoto, Sandra G. ^[1] ; Aikawa, Nadia E. ^{[1, 2]} ; Yuki, Emily F. N. ^[1] ; Borba, Eduardo F. ^[1] ; Ferreira Filho, Julio C. R. ^{[1, 3]} ; Carricondo, Pedro C. ^[4] ; Zanetti, Caio B. ^[1] ; Conde, Paola G. ^[1] ; Duarte, Nilo J. C. ^[3] ; Fontoura, Nicole ^[1] ; Romano, Paschoalina ^[3] ; Carvalho, Valdemir M. ^[5] ; Silva, Clovis A. ^[2] ; Bonfa, Eloisa ^[1]

Affiliation

^[1] Univ Sao Paulo, Hosp Clin, Rheumatol Div, Fac Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Pediat Rheumatol Unit, Fac Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Hosp Clin, Div Cent Lab, Fac Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin, Ophtalmol Div, Fac Med, Sao Paulo - Brazil

^[5] Fleury Grp, Sao Paulo - Brazil

• Document type: Journal article
• Source: Lupus; v. 29, n. 6 MAR 2020.
• Web of Science Citations: 0

Abstract

Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4-5.5 mg/kg actual body weight (maximum 400 mg/day) for >= 3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase >= 3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5-1471.1) vs. 1006.3 (53.5-2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66-45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar's test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels. (AU)

• 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: 17/11516-9 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Julio Cesar Rente Ferreira Filho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/11854-1 - Assessment of serum levels of anti-tumor necrosis factor (anti-TNF) and anti-drug antibodies (ADA) in patients with chronic inflammatory arthritis: ankylosing spondylitis and psoriatic arthritis
• Grantee: Paola Giulia Conde
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• 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: 17/11644-7 - Blood and salivary levels of hydroxychloroquine: relevance in juvenile systemic lupus erythematosus disease (JSLE), in kidney disease in adult SLE activity and in alpha-interferon / TNF production by plasmacytoid dendritic cells
• Grantee: Nicole Andressa Gomes Fontoura
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training