PATCH study: Hydroxychloroquine may prevent recurrence of congenital heart block in neonates
ATLANTA — Among mothers with anti-Ro antibodies who had previously delivered a baby with congenital heart block, hydroxychloroquine was associated with a 50% in risk of that complication in subsequent pregnancies, according to a speaker at ACR/ARP 2019.
“Mothers with lupus or who generate anti-Ro antibodies can cause a number of comorbidities, including congenital heart block and skin rash,” Peter Izmirly, MD, a rheumatologist at the NYU School of Medicine, said in a press conference. In addition to SLE, mothers with Sjögren’s syndrome also produce these antibodies. “Asymptomatic women also can have anti-Ro antibodies, but we often do not discover them until babies with congenital heart block are worked up.”
Congenital heart block (CHB) is associated with considerable morbidity and mortality, with up to 70% or 80% of patients requiring lifelong pacing. Heart failure is a common complication of this condition, and patients often require transplant.
“There are no effective treatments for CHB,” Jill Buyon, MD, a rheumatologist at the NYU School of Medicine, said in a presentation to the general assembly. “Given the irreversible nature of this condition, the optimal approach is prevention.”
Previous data have shown that in women who have one child with CHB, the risk for CHB in a second or third child is increased. Izmirly said that the group began thinking of hydroxychloroquine as a potential mitigator of the risk for this condition decades ago. “Earlier data showed that mothers on hydroxychloroquine had children with a risk of developing heart block was less than controls,” he said. “We wondered: could you reduce the recurrence rate by 20%?”
The current study employed a two-stage approach. In the first stage, the group accrued 19 pregnant women. If three or more mothers delivered children with CHB, the study would be deemed unsuccessful, and terminated. If fewer than three mothers had children with CHB, the group would recruit 35 more mothers. At the end, if fewer than six of the 54 mothers had babies with CHB, the study would be deemed successful.
Eligible mothers included women with a previous child with CHB and a positive test for anti-Ro antibodies, but who did not fulfill criteria for SLE or Sjögren’s syndrome. “Half of the cohort was asymptomatic,” Izmirly said.
Treatment protocols called for hydroxychloroquine initiation or maintenance at 400 mg by 10 weeks of gestation. Mothers also underwent regular echocardiograms, and had blood drawn to measure antibody levels and hydroxychloroquine in cord blood.
The primary endpoint was recurrence of second- or third-degree heart block in utero or at birth. Secondary endpoints included a first-degree block at birth, change in heart rhythm, rash, or infants who were small for gestational age.
Enrollment occurred between 2011 and 2018.
In the first stage of the study, 17 pregnancies had no CHB, while two infants had CHB. The study then progressed to the second stage, at which point 33 of the 35 pregnancies did not have CHB.
Overall, four out of 54 pregnancies, or 7.4%, resulted in an advanced block, which Izmirly reported was considerably more than the 20% reduction necessary to call the study a success.
Secondary endpoints showed four rashes and nine births before 37 weeks.
Monitoring of hydroxychloroquine indicated that at some point, all mothers were compliant with the study drug. “Cord blood levels unambiguously demonstrated hydroxychloroquine exposure,” Buyon said.
“Hydroxychloroquine reduced the historical rate of CHB by 50%,” Izmirly said.
Buyon added a comment on the translational implications of the study. “These findings support the consideration of hydroxychloroquine for secondary prevention of advanced conduction defects,” she said, adding that testing all pregnancies for anti-Ro antibodies, regardless of maternal health, may also help prevent CHB. – by Rob Volansky
Izmirly P. Abstract #1761. The Prospective Open Label Preventive Approach to Congenital Heart Block with Hydroxychloroquine (PATCH) Study demonstrates a reduction in the recurrence rate of advanced block. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Buyon reports associations with Bristol Myers Squibb and Exagen Diagnostics. Izmirly reports associations with GlaxoSmithKline.