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Observational Study
. 2025 Mar 1;64(3):1225-1233.
doi: 10.1093/rheumatology/keae302.

Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in systemic lupus erythematosus patients

Gelsomina Alle  1   2 , Gaëlle Guettrot-Imbert  1 , Maddalena Larosa  3 , Anne Murarasu  1   4   5 , Estibaliz Lazaro  6 , Nathalie Morel  1 , Pauline Orquevaux  7 , Laurent Sailler  8 , Viviane Queyrel  9 , Eric Hachulla  10 , Françoise Sarrot Reynauld  11 , Laurent Pérard  12 , Alice Bérezné  13 , Chafika Morati-Hafsaoui  13 , Elodie Chauvet  14 , Christophe Richez  15 , Tiphaine Goulenok  16 , Jonathan London  1 , Anna Molto  17 , Geoffrey Urbanski  18 , Maëlle Le Besnerais  19 , Vincent Langlois  20 , Gaëlle Leroux  21 , Odile Souchaud-Debouverie  22 , Céline Lartigau Roussin  23 , Vincent Poindron  24 , Benoit Blanchet  25 , Emmanuelle Pannier  26 , Loïc Sentilhes  27 , Luc Mouthon  1 , Véronique Le Guern  1 , Nathalie Costedoat-Chalumeau  1 ; GR2 Study Group
Affiliations
Observational Study

Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in systemic lupus erythematosus patients

Gelsomina Alle et al. Rheumatology (Oxford). .

Abstract

Objectives: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole-blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE).

Methods: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole-blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates).

Results: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, four (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, P = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, P = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, P = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, P = 0.04) had significantly more severe flares.

Conclusion: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs.

Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02450396.

Keywords: adverse pregnancy outcomes; hydroxychloroquine; maternal flares; pregnancy; systemic lupus erythematosus; therapeutic drug monitoring.

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Figures

Figure 1.
Figure 1.
Study flowchart. GR2: Groupe de Recherche sur la Grossesse et les Maladies Rares; HCQ: hydroxychloroquine; SLE: systemic lupus erythematosus
Figure 2.
Figure 2.
Severe maternal flares and APOs according to different thresholds for HCQ blood levels. (A) Therapeutic threshold (therapeutic >500 ng/mL; subtherapeutic ≤500 ng/mL). (B) Adherence threshold (adherence >200 ng/mL; non-adherence ≤200 ng/mL). APOs: adverse pregnancy outcomes; HCQ: hydroxychloroquine
See this image and copyright information in PMC

References

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