A recent trial evaluated the effect of hydroxychloroquine (HCQ) on the recurrence of congenital heart block (CHB) in pregnant patients with systemic lupus erythematosus (SLE). The findings of the study were presented during a plenary session at the ACR/ARP Annual Meeting.
“Based on encouraging bench to bedside results, including experimental evidence supporting Toll-like receptor signaling in the pathogenesis of CHB, a case-control study demonstrating CHB risk reduction in HCQ exposed fetuses of anti-Ro-positive SLE women, and a historical cohort study supporting a reduction in recurrence rate, an open-label, single-arm, phase II clinical trial was initiated to evaluate whether HCQ reduces the CHB recurrence rate (π) below the historical recurrence rate of 18%,” the researchers explained in the abstract.
This two-stage trial (first stage, n=19; second stage, n=54) employed Simon’s optimal approach to allow patients to exit the study early if treatment efficacy was not observed. The primary outcome was mothers with a previous CHB child having a subsequent child with second- or third-degree block. HCQ initiation or maintenance at 400 mg was required by week 10 of pregnancy. Evaluation included serial echocardiograms and blood drawn at each trimester and delivery to measure antibody and HCQ levels.
Among 65 pregnant mothers with previous CHB children and anti-Ro52 or -Ro60 > 1,000 EU who consented to the trial, 10 were ultimately not included and one was lost to follow-up before delivery; 54 pregnancies were included in the final analysis. Two of the 19 fetuses in stage one had CHB; in total, four of the 54 pregnancies presented with CHB, all at 19 to 20 weeks.
“Our translational implications of the data from this prospective, single-arm clinical trial support the consideration of HCQ for secondary prevention of advanced conduction defects,” said Jill Buyon, MD, professor of medicine and director of the Lupus Center at New York University School of Medicine/New York University Langone Health, who presented the findings. “Given the potential benefit of HCQ, we suggest that testing all pregnancies for anti-Ro antibodies, regardless of maternal health, should be considered.”