TY - JOUR
T1 - Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers
AU - Izmirly, Peter
AU - Kim, Mimi
AU - Friedman, Deborah M.
AU - Costedoat-Chalumeau, Nathalie
AU - Clancy, Robert
AU - Copel, Joshua A.
AU - Phoon, Colin K.L.
AU - Cuneo, Bettina F.
AU - Cohen, Rebecca E.
AU - Robins, Kimberly
AU - Masson, Mala
AU - Wainwright, Benjamin J.
AU - Zahr, Noel
AU - Saxena, Amit
AU - Buyon, Jill P.
N1 - Publisher Copyright:
© 2020 American College of Cardiology Foundation
PY - 2020/7/21
Y1 - 2020/7/21
N2 - Background: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). Objectives: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. Methods: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. Results: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). Conclusions: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies.
AB - Background: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). Objectives: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. Methods: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. Results: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). Conclusions: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies.
KW - anti-SSA/Ro antibodies
KW - congenital heart block
KW - hydroxychloroquine
KW - neonatal lupus
KW - prevention
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U2 - 10.1016/j.jacc.2020.05.045
DO - 10.1016/j.jacc.2020.05.045
M3 - Article
C2 - 32674792
AN - SCOPUS:85087400373
SN - 0735-1097
VL - 76
SP - 292
EP - 302
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 3
ER -