Exposure to latent tuberculosis treatment during pregnancy the PREVENT TB and the iadhere trials

Ruth N. Moro, Nigel A. Scott, Andrew Vernon, Naomi K. Tepper, Stefan V. Goldberg, Kevin Schwartzman, Chi Chiu Leung, Neil W. Schluger, Robert W. Belknap, Richard E Chaisson, Masahiro Narita, Elizabeth S. Machado, Marta Lopez, Jorge Sanchez, Margarita E. Villarino, Timothy R. Sterling

Research output: Contribution to journalReview article

Abstract

Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). Methods: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% 2 14% = 21%; 95% confidence interval = 217% to 118%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% 2 5% = 25%; 95% confidence interval = 218% to 116%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of childbearing potential.

Original languageEnglish (US)
Pages (from-to)570-580
Number of pages11
JournalAnnals of the American Thoracic Society
Volume15
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Latent Tuberculosis
Pregnancy
rifapentine
Isoniazid
Live Birth
Therapeutics
Pharmaceutical Preparations
Confidence Intervals
Safety
Pregnancy Outcome
Pregnant Women
Infection

Keywords

  • Latent tuberculosis infection treatment
  • Pregnancy outcomes
  • Safety assessment

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Moro, R. N., Scott, N. A., Vernon, A., Tepper, N. K., Goldberg, S. V., Schwartzman, K., ... Sterling, T. R. (2018). Exposure to latent tuberculosis treatment during pregnancy the PREVENT TB and the iadhere trials. Annals of the American Thoracic Society, 15(5), 570-580. https://doi.org/10.1513/AnnalsATS.201704-326OC

Exposure to latent tuberculosis treatment during pregnancy the PREVENT TB and the iadhere trials. / Moro, Ruth N.; Scott, Nigel A.; Vernon, Andrew; Tepper, Naomi K.; Goldberg, Stefan V.; Schwartzman, Kevin; Leung, Chi Chiu; Schluger, Neil W.; Belknap, Robert W.; Chaisson, Richard E; Narita, Masahiro; Machado, Elizabeth S.; Lopez, Marta; Sanchez, Jorge; Villarino, Margarita E.; Sterling, Timothy R.

In: Annals of the American Thoracic Society, Vol. 15, No. 5, 01.05.2018, p. 570-580.

Research output: Contribution to journalReview article

Moro, RN, Scott, NA, Vernon, A, Tepper, NK, Goldberg, SV, Schwartzman, K, Leung, CC, Schluger, NW, Belknap, RW, Chaisson, RE, Narita, M, Machado, ES, Lopez, M, Sanchez, J, Villarino, ME & Sterling, TR 2018, 'Exposure to latent tuberculosis treatment during pregnancy the PREVENT TB and the iadhere trials', Annals of the American Thoracic Society, vol. 15, no. 5, pp. 570-580. https://doi.org/10.1513/AnnalsATS.201704-326OC
Moro, Ruth N. ; Scott, Nigel A. ; Vernon, Andrew ; Tepper, Naomi K. ; Goldberg, Stefan V. ; Schwartzman, Kevin ; Leung, Chi Chiu ; Schluger, Neil W. ; Belknap, Robert W. ; Chaisson, Richard E ; Narita, Masahiro ; Machado, Elizabeth S. ; Lopez, Marta ; Sanchez, Jorge ; Villarino, Margarita E. ; Sterling, Timothy R. / Exposure to latent tuberculosis treatment during pregnancy the PREVENT TB and the iadhere trials. In: Annals of the American Thoracic Society. 2018 ; Vol. 15, No. 5. pp. 570-580.
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abstract = "Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). Methods: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13{\%}) and 8/56 (14{\%}), 3HP and 9H, respectively (difference, 13{\%} 2 14{\%} = 21{\%}; 95{\%} confidence interval = 217{\%} to 118{\%}) and congenital anomalies in 0/20 and 2/41 (5{\%}) live births, 3HP and 9H, respectively (difference, 0{\%} 2 5{\%} = 25{\%}; 95{\%} confidence interval = 218{\%} to 116{\%}). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15{\%}) and 9/72 (13{\%}), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3{\%}) and 2/56 (4{\%}) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13{\%}]) and anomalies (3/93 [3{\%}]) were similar to those estimated for the United States, 17{\%} and 3{\%}, respectively. Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of childbearing potential.",
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AU - Scott, Nigel A.

AU - Vernon, Andrew

AU - Tepper, Naomi K.

AU - Goldberg, Stefan V.

AU - Schwartzman, Kevin

AU - Leung, Chi Chiu

AU - Schluger, Neil W.

AU - Belknap, Robert W.

AU - Chaisson, Richard E

AU - Narita, Masahiro

AU - Machado, Elizabeth S.

AU - Lopez, Marta

AU - Sanchez, Jorge

AU - Villarino, Margarita E.

AU - Sterling, Timothy R.

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N2 - Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). Methods: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% 2 14% = 21%; 95% confidence interval = 217% to 118%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% 2 5% = 25%; 95% confidence interval = 218% to 116%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of childbearing potential.

AB - Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). Methods: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% 2 14% = 21%; 95% confidence interval = 217% to 118%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% 2 5% = 25%; 95% confidence interval = 218% to 116%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of childbearing potential.

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