1. Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.
- Author
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Izmirly, Peter, Kim, Mimi, Friedman, Deborah M, Costedoat-Chalumeau, Nathalie, Clancy, Robert, Copel, Joshua A, Phoon, Colin K L, Cuneo, Bettina F, Cohen, Rebecca E, Robins, Kimberly, Masson, Mala, Wainwright, Benjamin J, Zahr, Noel, Saxena, Amit, and Buyon, Jill P
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AUTOANTIBODIES , *RESEARCH , *CLINICAL trials , *ORAL drug administration , *RESEARCH methodology , *EVALUATION research , *MEDICAL cooperation , *HEART block , *FETAL diseases , *COMPARATIVE studies , *DOSE-effect relationship in pharmacology , *HYDROXYCHLOROQUINE , *LONGITUDINAL method , *ENZYME inhibitors ,DISEASE relapse prevention - Abstract
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. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573). [ABSTRACT FROM AUTHOR]- Published
- 2020
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