Advances in the Clinical Use of Hydroxychloroquine Levels

Katherine Chakrabarti; W. Joseph McCune


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

In This Article

Hydroxychloroquine Levels and Disease Activity

Multiple studies have correlated higher disease activity with lower hydroxychloroquine levels.[10,13,14,16–19] This data is well synthesized in the excellent meta-analysis by Garg et al. Hydroxychloroquine levels reported varied widely with no consensus on appropriate level adequate for treatment. Hydroxychloroquine levels of at least 750 ng/ml predicted a 58% lower risk of active lupus.[12]

Blanchet et al.[5] in 2020 reported that whole blood levels were higher in patients with low disease activity (SLEDAI ≤4) vs. high disease activity (SLEDAI > 4) (940.8 ± 448 vs. 765.9 ± 426 ng/ml, P = 0.001). Geraldino-Paradilla et al. (2019) evaluated 108 patients with SLE and found that patients who were nonadherent by their definition (defined as a hydroxychloroquine level ≤500 ng/ml) had a higher SLEDAI-2K score compared with those who were adherent (5.7 vs. 3.2).[10] Iudici et al. in 2018 reported that the 5 of 83 lupus patients who flared during a 6 month follow-up period had a lower median hydroxychloroquine level at baseline compared with those who did not experience a flare (284 vs. 435 ng/ml).[20]

Two recent studies of lupus nephritis reported that persistent values above a target hydroxychloroquine level were correlated with lower likelihood of lupus nephritis flare. In the first study of 171 patients with class III, IV, or V lupus nephritis not on renal replacement therapy, no correlation between hydroxychloroquine levels and lupus nephritis flares was identified.[17] In patients with active nephritis at baseline the hydroxychloroquine levels of patients who went into remission were similar to those who continued to have active disease (P = 0.23). In patients with partial or complete remission at inclusion, the hydroxychloroquine levels were lower in those who experienced a renal flare during the follow-up period (0.59 vs. 0.81 mg/l, P = 0.005). The data suggested that a target hydroxychloroquine level of greater than 600 ng/ml reduces the likelihood of lupus nephritis flares.[17] Pedrosa et al.[18] reported that persistently low hydroxychloroquine levels were associated with higher risk of lupus nephritis flares in a study of 82 patients. A hydroxychloroquine level less than 613.5 ng/ml best predicted risk of flare in a study of 82 patients with lupus nephritis.[18] Table 1 summarizes recent study conclusions.

In assessments of dermatologic disease with use of the CLASI, arguably the most objective lupus disease activity measurement, Chasset et al.[21] reported that increased HCQ dose and HCQ levels were associated with a statistically significant decrease in both CLASI and RCLASI score (P values <0.001 for both). Frances et al.[22] did not report a CLASI score but concluded that hydroxychloroquine levels correlated with cutaneous disease remission in both univariate and multivariate analyses.