Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in systemic lupus erythematosus patients
Authors: Alle Gelsomina , Guettrot-Imbert Gaëlle , Larosa Maddalena , Murarasu Anne , Lazaro Estibaliz , Morel Nathalie , Orquevaux Pauline , Sailler Laurent , Queyrel Viviane , Hachulla Eric , Sarrot Reynauld Françoise , Pérard Laurent , Bérezné Alice , Morati-Hafsaoui Chafika , Chauvet Elodie , Richez Christophe , Goulenok Tiphaine , London Jonathan , Molto Anna , Urbanski Geoffrey , Le Besnerais Maëlle , Langlois Vincent , Leroux Gaëlle , Souchaud-Debouverie Odile , Roussin Céline Lartigau , Poindron Vincent , Blanchet Benoit , Pannier Emmanuelle , Sentilhes Loïc , Mouthon Luc , Le Guern Véronique , Costedoat-Chalumeau Nathalie ,   GR2 Study Group, Absiror Noémie , Azzi Emmanuel , Banneville Béatrice , Baudet Antoine , Beaudouin-Bazire Constance , Belizna Cristina , Belkhir Rakiba , Benhamou Ygal , Berthoux Emilie , Berthier Sabine , Bezanahary Holy , Biale Lisa , Bienvenu Boris , Bigot Adrien , Blanchard-Delaunay Claire , Calas Anne , Cathebras Pascal , Cazalets Claire , Chaigne Benjamin , Chandesris Olivia , Chatelais Jérémy , Chatelus Emmanuel , Cohen Fleur , Coquerelle Pascal , Couderc Marion , De Menthon Mathilde , De Moreuil Claire , Delattre Estelle , Delforge Juliette , Dellal Azeddine , Denis Amélie , Deprouw Camille , Dernis Emmanuelle , Deroux Alban , Desouches Sandra , Dieudé Philippe , Diot Elisabeth , Direz Guillaume , Driessen Marine , Du Thanh Aurélie , Dunogeant Laetitia , Durant Cécile , Durieu Isabelle , Eboue Florence , Fabre Marc , Fain Olivier , Fautrel Bruno , Ferreira-Maldent Nicole , Flipo René-Marc , Frazier Aline , Froissart Antoine , Georgin-Lavialle Sophie , Gervais Elisabeth , Godeau Bertrand , Gompel Anne , Gossec Laure , Goupille Phillipe , Grange Claire , Guillaud-Danis Constance , Hummel Aurélie , Jallouli Moez , Jego Patrick , Jobard Stéphanie , Josselin-Mahr Laurence , Jourde-Chiche Noémie , Korganow Anne-Sophie , Lambert Marc , Lariviere Delphine , Larroche Claire , Latourte Augustin , Lavigne Christian , Le Gallou Thomas , Levesque Hervé , Limal Nicolas , Lioté Frédéric , Loustau Valentine , Maheu Emmanuel , Mahevas Matthieu , Maillard Hélène , Mariette Xavier , Marotte Hubert , Martin-Silva Nicolas , Martis Nihal , Masseau Agathe , Maurier François , Mekinian Arsène , Melboucy-Belkhir Sara , Michaud Martin , Michel Marc , Moulis Guillaume , Nizard Jacky , Ora Jérémy , Outh Rodérau , Pasquier Elisabeth , Pennaforte Jean-Loup , Perlat Antoinette , Bauer Hélène Petit , Pillebout Evangeline , Piot Jean-Maxime , Portier Agnès , Puechal Xavier , Pugnet Gregory , Raffray Loic , Redondin Manon , Regent Alexis , Roriz Mélanie , Sauvêtre Gaëtane , Savey Léa , Schleinitz Nicolas , Seror Raphaele , Servais Aude , Smets Perrine , Sobanski Vincent , Sordet Christelle , Soubrier Martin , Stojanovic Katia Stankovic , Thomas Thierry , Tieulé Nathalie , Timsit Marie-Agnès , Tsatsaris Vassilis , Weber Emmanuelle , Yelnik Cécile 
Published: June 2024

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 &gt;500 ng/ml: 23.5% vs 14.3%, P = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs &gt;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