Advances in the Clinical Use of Hydroxychloroquine Levels

Katherine Chakrabarti; W. Joseph McCune

Curr Opin Rheumatol. 2022;34(3):151-157.

Abstract and Introduction

Abstract

Purpose of Review: This review summarizes the recent literature exploring hydroxychloroquine levels and their relationship with disease activity and risk of toxicity.

Recent Findings: There is no clear correlation between weight-based dosing of hydroxychloroquine and the resulting blood levels of the medication. Recent studies have shown that increased hydroxychloroquine levels are associated with lower lupus disease activity and likely also increased risk of medication toxicity.

Summary: Mounting evidence supports use of hydroxychloroquine levels in clinical practice to document adherence and ensure safety.

Introduction

Studies correlating hydroxychloroquine levels with control of lupus activity suggest that the association of higher levels with a favorable outcome may be both causal – resulting from benefit of achieving high levels – and that lower levels may indicate noncompliance. Conversely, studies of the association of levels with toxicity take into account levels achieved regardless of compliance. Articles from Petri et al. suggest there is no clear correlation between prescribed weight-based dosing of hydroxychloroquine and the resulting blood level in an individual (Figure 1) emphasizing the potential utility of following blood levels of hydroxychloroquine (HCQ) rather than relying on administrating a calculated dose. This review summarizes new literature published since an earlier review published in this journal in 2018.^[1] The data available to date support the use of hydroxychloroquine levels in clinical practice both to help achieve therapeutic levels and reduce risk of toxicity.

(Enlarge Image)

Figure 1.

There is no strong correlation between a weight-based dose of hydroxychloroquine and the resultant hydroxychloroquine blood level. Reproduced with permission from Petri et al. [23].

1 2 3 4 5 6 7 8 9 10 11 12

Next Section

Table 1. Summary and conclusions of recent studies evaluating hydroxychloroquine levels in SLE patients
Author (year)	Study population	Comparator groups	Conclusion
Blanchet et al. (2020)	SLE patients on hydroxychloroquine for ≥6 months without dose modification in ≥2 months	Low disease activity: SLEDAI ≤4High disease activity: SLEDAI >4	Whole blood levels were higher in patients with low disease activity (940.8 ± 448 vs. 765.9 ± 426 ng/ml, P = 0.001)
Geraldino-Paradilla et al. (2019)	SLE patients on hydroxychloroquine for ≥6 months who reported medication adherence	Hydroxychloroquine level ≤500 ng/ml vs. hydroxychloroquine level >500 ng/ml	SLEDAI-2K score higher in those who had level ≤500 ng/ml compared with adherent to hydroxychloroquine (5.7 vs. 3.2)
Iudici et al. (2018)	SLE patients in remission for >1 year and taking stable dose of hydroxychloroquine	Patients with flare vs. no flare over 6-month period based on SELENA-SLEDAI score	Median baseline hydroxychloroquine level lower in patients who experienced a flare over a 6 month period (284 vs. 435 ng/ml, P = 0.225)
Cunha et al. (2018)	Biopsy-proven class III, IV or V lupus nephritis on hydroxychloroquine for ≥3 months	Patients with flare vs. patients with no flare	In patients with active nephritis at baseline the hydroxychloroquine levels of those who received remission was similar to those who continued to have active disease. In patients in complete or partial remission at baseline, patients who experienced a renal flare had lower average hydroxychloroquine levels
Pedrosa et al. (2020)	Lupus nephritis patients	Patients with flare vs. patients with no flare	Flares were found to be more frequent in patients with hydroxychloroquine level <613.5 ng/ml (28 vs. 5%, P = 0.023)

SELENA-SLEDAI, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index.