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 in Pregnancy

The guidelines for the treatment of SLE in pregnancy recommend hydroxychloroquine as first-line treatment. It is highly likely that the use of hydroxychloroquine in lupus pregnancies has contributed to lower rates of preterm delivery,[36] intra-uterine grown restriction,[36,37] preeclampsia,[37] and lupus flares.[36,38] Additionally, lupus flares are predicted by hydroxychloroquine discontinuation during pregnancy.[39]

In addition to controlling disease activity and decreasing flares, hydroxychloroquine has the potential benefit of decreasing the risk of congenital heart block based on observational data from the PATCH study in which +Ro/SSA mothers with a prior pregnancy complicated by complete heart block were treated with hydroxychloroquine 400 mg daily.[40] Hydroxychloroquine is also recommended for use with any history of obstetric or thrombotic APS to decrease the risk of thrombosis.[41]

A recent observational analysis of 50 patients with rheumatic diseases enrolled in the Duke Autoimmunity in Pregnancy registry evaluated the association between hydroxychloroquine levels and premature delivery. Fifty-six percent of the patients included had underlying lupus. Of the patients with SLE, premature deliveries occurred with both hydroxychloroquine levels less than 100 ng/ml and greater than 500 ng/ml although the frequency of premature birth was much greater in the group with the lower hydroxychloroquine level (83 vs. 21%).[42] In an ACR abstract published around this time by the same research group, the authors hypothesize that hydroxychloroquine levels of 101–500 ng/ml by their assay is ideal. They did also note that hydroxychloroquine levels decline as pregnancy progresses, with a nadir in the third trimester.[43] Given the wide variety of levels reported in the literature, further work is needed to investigate this issue.

Another article from the Duke Autoimmunity in Pregnancy registry data sought to understand the complex physiology of hydroxychloroquine levels during pregnancy including 50% increase in blood volume, increased adipose tissue, and changes in glomerular filtration, which can have marked effects on drug metabolism. The authors concluded that although the volume of distribution of hydroxychloroquine increased with the changes of progression through pregnancy, the total drug exposure did not change when compared with the same group postpartum.[44]