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Prevention of congenital heart block may be possible with hydroxychloroquine

Presented by
Prof. Peter Izmirly, New York University School of Medicine, USA
ACR 2019
Treatment with hydroxychloroquine significantly reduced the recurrence rate of congenital heart block (CHB) for children of mothers with a previous child affected [1].

CHB is one of the clinical manifestations of neonatal lupus syndrome [2]. It is associated with a 17.5% mortality and 70% requirement of permanent pacing [3]. The disease is induced by a placental transport of maternal anti-SSA/Ro antibodies [2]. Women carrying these antibodies may have systemic lupus erythematosus, Sjögren syndrome, or other connective tissue diseases, or may be completely healthy at the time of giving birth [2].
“CHB affects an estimated 2% of pregnancies among women who have anti-SSA/Ro antibodies who have never been pregnant or have never had an affected child. It appears maternal health accompanying the production of the candidate autoantibodies is not a risk factor for foetal disease, since many mothers whose foetuses develop cardiac injury are asymptomatic and often learn of anti-SSA/Ro antibodies solely based on disease in their children,” explained Prof. Peter Izmirly (New York University School of Medicine, USA). Once an affected child is born, the risk for the next child rises dramatically and has been found to climb up to 18% for subsequent babies to be born suffering from CHB [3]. Given the high mortality of CHB, the optimal approach is prevention.

The PATCH study was performed to find out if hydroxychloroquine could lower recurrence rates of CHB below the historical mark of 18%. The single-arm phase 2 trial was designed in 2 stages to take an early study stop into consideration in case of inefficacy of hydroxychloroquine. Stage 1 included 19 and stage 2 an additional 35 currently pregnant women who were all anti-SSA/Ro positive and had given birth to a child with CHB before. Treatment was initiated with 400 mg of hydroxychloroquine daily by 10 weeks of gestation. Surveillance during pregnancy was performed by sequential echocardiograms for PR intervals, advanced block, and cardiomyopathy. Furthermore, compliance was checked by measurement of hydroxychloroquine levels every trimester and within the cord blood. Treatment adherence was confirmed in 98% of the mothers. Primary outcome was second-/third-degree block in utero or at birth.

In the first stage, only 2 children were diagnosed with CHB, and so the trial proceeded to stage 2 in which 2/35 enrolled mothers gave birth to a child with CHB. Per intention-to-treat analysis of both stages, in 7.4% (4/54) an outcome with CHB was found, leading to a significant result in favour of hydroxychloroquine (P=0.02). “Our group has previously reported in a historical cohort that the use of hydroxychloroquine may be associated with a reduced recurrence rate of CHB, but this is the first prospective study to confirm those findings,” Prof. Izmirly pointed out. “Given the morbidity and mortality associated with the disease and the relative safety of hydroxychloroquine use during pregnancy, a treating physician should consider using hydroxychloroquine to reduce the risk of CHB in a mother who has had a previously affected child,” he concluded.

    1. Izmirly P, et al. Abstract 1761. ACR 2019. 8-13 November, Atlanta (GA/USA).
    2. Zuppa AA, et al. Autoimmun Rev. 2017;16:427-432.
    3. Izmirly P, et al. Circulation. 2011;124:1927-35.

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