Disclosures: The authors report no relevant financial disclosures.
July 14, 2020
2 min read

Hydroxychloroquine halves recurrence of fetal heart block

Disclosures: The authors report no relevant financial disclosures.
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In a cohort of pregnant women with prior maternal congenital heart block, hydroxychloroquine successfully reduced the risk for recurrent fetal blocks by more than 50%, according results from the PATCH trial.

“To date, there are no effective therapies once a fetus develops third-degree block and the mortality rate approaches 18% and 70% of children require pacemaker placement,” Peter Izmirly, MD, associate professor at New York University School of Medicine, told Healio. “In this open-label prospective trial, hydroxychloroquine 400 mg daily initiated at or before 10 weeks’ gestation was associated with a greater than 50% reduction of the recurrence rate of congenital heart block.”

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Trial design

For the first stage of this two-stage single-arm analysis, published in the Journal of the American College of Cardiology, investigators enrolled 19 patients who were treated with 400 mg hydroxychloroquine daily from before completion of week 10 of gestation through completion of pregnancy. The primary outcome was second- or third-degree congenital heart block.

If fewer than three participants developed fetal congenital heart block, researchers planned to enroll 35 more pregnant women for the second stage of the trial (n = 54).

If six or more fetuses developed congenital heart block, investigators would terminate the trial early.

According to the study background, the historical recurrence rate of congenital heart block among pregnant women with prior maternal anti-SSA/Ro-mediated block is at least 18%.

Researchers observed that a second-degree block developed in only two pregnancies, at 19 weeks and 18 weeks, and therefore the trial proceeded to stage two, in which two more fetuses developed congenital heart block.

Between stages one and two, the recurrence rate for congenital heart block was 7.4% (90% CI, 3.4-15.9).

Moreover, among all 63 pregnancies evaluated in this trial, cutaneous neonatal lupus arose in four cases (6.4%; 90% CI, 2.2-13.4), and in nine pregnancies, birth occurred at less than 37 weeks’ gestation (14.3%; 90% CI, 7.7-23.6).

“This study opens the consideration of testing all pregnant women for these antibodies if there is a potential prevention,” Izmirly told Healio. “In addition, this study is leveraging this unique opportunity in which maternal and cord blood levels of hydroxychloroquine have been obtained. An anatomical survey of the retina is being performed via OCT in children with substantiated drug exposure who have reached age 5. These data are expected to provide further evidence regarding the long-term safety of hydroxychloroquine use during pregnancy with impact extending beyond secondary congenital heart block prevention, since all patients with systemic lupus erythematosus are advised to take hydroxychloroquine during pregnancy.”

The treatment population

“At this time, hydroxychloroquine is indicated (based on the recommendations of Izmirly et al) for prophylaxis in patients with a high risk for recurrent fetal congenital heart block because the lifelong risk of morbidity is substantial and probably outweighs the risk of hydroxychloroquine to either mother or fetus,” Janette F. Strasburger, MD, professor in the department of pediatrics in the division of cardiology at Children’s Wisconsin in Milwaukee, and Annette Wacker-Gussmann, MD, in the department of pediatric cardiology and congenital heart disease at the German Heart in Munich, wrote in a related editorial. “However, they did not recommend the use of hydroxychloroquine in the low-risk population of SSA patients, especially those with low titers and no active disease. Even if one were to use it in the patient with active lupus or high SSA titers in the absence of prior fetal heart block, it should primarily be for the mother’s benefit and with open discussion of the risks. Given a 50% decrease, it would be necessary to treat 100+ low-risk SSA-positive pregnancies with hydroxychloroquine to prevent just one case of congenital atrioventricular block.”