Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open-label clinical trial

Deborah M. Friedman, Carolina Llanos, Peter M. Izmirly, Brigit Brock, John Byron, Joshua Copel, Karen Cummiskey, Mary Anne Dooley, Jill Foley, Cornelia Graves, Colleen Hendershott, Richard Kates, Elena V. Komissarova, Michelle Miller, Emmanuelle Paré, Colin K L Phoon, Tracy Prosen, Dale Reisner, Eric Ruderman, Philip SamuelsJerry K. Yu, Mimi Kim, Jill P. Buyon

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Objective. The recurrence rate of anti-SSA/Ro - associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. Methods. A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with ≤20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB. Results. Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. Conclusion. This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.

Original languageEnglish (US)
Pages (from-to)1138-1146
Number of pages9
JournalArthritis and Rheumatism
Volume62
Issue number4
DOIs
StatePublished - Apr 2010

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Intravenous Immunoglobulins
Fetus
Clinical Trials
Mothers
Therapeutics
Exanthema
Congenital heart block
Parturition
Fetal Monitoring
Safety
Recurrence
Antibodies
Prednisone
Autoantibodies
Pregnant Women
Pregnancy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block : Results of a multicenter, prospective, open-label clinical trial. / Friedman, Deborah M.; Llanos, Carolina; Izmirly, Peter M.; Brock, Brigit; Byron, John; Copel, Joshua; Cummiskey, Karen; Dooley, Mary Anne; Foley, Jill; Graves, Cornelia; Hendershott, Colleen; Kates, Richard; Komissarova, Elena V.; Miller, Michelle; Paré, Emmanuelle; Phoon, Colin K L; Prosen, Tracy; Reisner, Dale; Ruderman, Eric; Samuels, Philip; Yu, Jerry K.; Kim, Mimi; Buyon, Jill P.

In: Arthritis and Rheumatism, Vol. 62, No. 4, 04.2010, p. 1138-1146.

Research output: Contribution to journalArticle

Friedman, DM, Llanos, C, Izmirly, PM, Brock, B, Byron, J, Copel, J, Cummiskey, K, Dooley, MA, Foley, J, Graves, C, Hendershott, C, Kates, R, Komissarova, EV, Miller, M, Paré, E, Phoon, CKL, Prosen, T, Reisner, D, Ruderman, E, Samuels, P, Yu, JK, Kim, M & Buyon, JP 2010, 'Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open-label clinical trial', Arthritis and Rheumatism, vol. 62, no. 4, pp. 1138-1146. https://doi.org/10.1002/art.27308
Friedman, Deborah M. ; Llanos, Carolina ; Izmirly, Peter M. ; Brock, Brigit ; Byron, John ; Copel, Joshua ; Cummiskey, Karen ; Dooley, Mary Anne ; Foley, Jill ; Graves, Cornelia ; Hendershott, Colleen ; Kates, Richard ; Komissarova, Elena V. ; Miller, Michelle ; Paré, Emmanuelle ; Phoon, Colin K L ; Prosen, Tracy ; Reisner, Dale ; Ruderman, Eric ; Samuels, Philip ; Yu, Jerry K. ; Kim, Mimi ; Buyon, Jill P. / Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block : Results of a multicenter, prospective, open-label clinical trial. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 4. pp. 1138-1146.
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AU - Friedman, Deborah M.

AU - Llanos, Carolina

AU - Izmirly, Peter M.

AU - Brock, Brigit

AU - Byron, John

AU - Copel, Joshua

AU - Cummiskey, Karen

AU - Dooley, Mary Anne

AU - Foley, Jill

AU - Graves, Cornelia

AU - Hendershott, Colleen

AU - Kates, Richard

AU - Komissarova, Elena V.

AU - Miller, Michelle

AU - Paré, Emmanuelle

AU - Phoon, Colin K L

AU - Prosen, Tracy

AU - Reisner, Dale

AU - Ruderman, Eric

AU - Samuels, Philip

AU - Yu, Jerry K.

AU - Kim, Mimi

AU - Buyon, Jill P.

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N2 - Objective. The recurrence rate of anti-SSA/Ro - associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. Methods. A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with ≤20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB. Results. Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. Conclusion. This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.

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