Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study

Timothy R. Sterling, Ruth N. Moro, Andrey S. Borisov, Elizabeth Phillips, Gillian Shepherd, Newton Franklin Adkinson, Stephen Weis, Christine Ho, Margarita Elsa Villarino, N. Franklin Adkinson, Jacques Grosset, Judith Hackman, Robert G. Hamilton, M. Elsa Villarino, Nong Shang, Fred Gordin, Awal Khan, Carol Dukes Hamilton, Dick Menzies, Amy Kerrigan & 11 others C. Robert Horsburgh, Richard E. Chaisson, George McSherry, Bert Arevalo, Andrew Vernon, David G. Kleinbaum, Charles Heilig, Kimberly Fryer, Isabelle Sanchez, Suet K. Lam, Nigel Scott

Research output: Contribution to journalArticle

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Abstract

Background. Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. Methods. We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. Results. Among 7552 persons who received 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P <. 001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P =. 009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1). Conclusions. SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.

Original languageEnglish (US)
Pages (from-to)527-535
Number of pages9
JournalClinical Infectious Diseases
Volume61
Issue number4
DOIs
StatePublished - Aug 15 2015

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rifapentine
Latent Tuberculosis
Isoniazid
Tuberculosis
Odds Ratio
Confidence Intervals
Pharmaceutical Preparations
Body Mass Index
Therapeutics
Syncope
Multivariate Analysis
Logistic Models
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Sterling, Timothy R. ; Moro, Ruth N. ; Borisov, Andrey S. ; Phillips, Elizabeth ; Shepherd, Gillian ; Adkinson, Newton Franklin ; Weis, Stephen ; Ho, Christine ; Villarino, Margarita Elsa ; Adkinson, N. Franklin ; Grosset, Jacques ; Hackman, Judith ; Hamilton, Robert G. ; Villarino, M. Elsa ; Shang, Nong ; Gordin, Fred ; Khan, Awal ; Hamilton, Carol Dukes ; Menzies, Dick ; Kerrigan, Amy ; Horsburgh, C. Robert ; Chaisson, Richard E. ; McSherry, George ; Arevalo, Bert ; Vernon, Andrew ; Kleinbaum, David G. ; Heilig, Charles ; Fryer, Kimberly ; Sanchez, Isabelle ; Lam, Suet K. ; Scott, Nigel. / Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. In: Clinical Infectious Diseases. 2015 ; Vol. 61, No. 4. pp. 527-535.
@article{15448d15519a4b2d9d013b81c4a61f3f,
title = "Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study",
abstract = "Background. Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. Methods. We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. Results. Among 7552 persons who received 1 dose of study drug, 153 had a SDR: 138/3893 (3.5{\%}) with 3HP vs 15/3659 (0.4{\%}) with 9H (P <. 001). In the 3HP arm, 87 (63{\%}) had flu-like syndrome and 23 (17{\%}) had cutaneous reactions; 13/3893 (0.3{\%}) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95{\%} confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95{\%} CI, 2.3, 4.7), female sex (aOR 2.0; 95{\%} CI, 1.4, 2.9), age 35 years (aOR 2.0; 95{\%} CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P =. 009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95{\%} CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95{\%} CI, 1.3, 27.1). Conclusions. SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.",
author = "Sterling, {Timothy R.} and Moro, {Ruth N.} and Borisov, {Andrey S.} and Elizabeth Phillips and Gillian Shepherd and Adkinson, {Newton Franklin} and Stephen Weis and Christine Ho and Villarino, {Margarita Elsa} and Adkinson, {N. Franklin} and Jacques Grosset and Judith Hackman and Hamilton, {Robert G.} and Villarino, {M. Elsa} and Nong Shang and Fred Gordin and Awal Khan and Hamilton, {Carol Dukes} and Dick Menzies and Amy Kerrigan and Horsburgh, {C. Robert} and Chaisson, {Richard E.} and George McSherry and Bert Arevalo and Andrew Vernon and Kleinbaum, {David G.} and Charles Heilig and Kimberly Fryer and Isabelle Sanchez and Lam, {Suet K.} and Nigel Scott",
year = "2015",
month = "8",
day = "15",
doi = "10.1093/cid/civ323",
language = "English (US)",
volume = "61",
pages = "527--535",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
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}

Sterling, TR, Moro, RN, Borisov, AS, Phillips, E, Shepherd, G, Adkinson, NF, Weis, S, Ho, C, Villarino, ME, Adkinson, NF, Grosset, J, Hackman, J, Hamilton, RG, Villarino, ME, Shang, N, Gordin, F, Khan, A, Hamilton, CD, Menzies, D, Kerrigan, A, Horsburgh, CR, Chaisson, RE, McSherry, G, Arevalo, B, Vernon, A, Kleinbaum, DG, Heilig, C, Fryer, K, Sanchez, I, Lam, SK & Scott, N 2015, 'Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study', Clinical Infectious Diseases, vol. 61, no. 4, pp. 527-535. https://doi.org/10.1093/cid/civ323

Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. / Sterling, Timothy R.; Moro, Ruth N.; Borisov, Andrey S.; Phillips, Elizabeth; Shepherd, Gillian; Adkinson, Newton Franklin; Weis, Stephen; Ho, Christine; Villarino, Margarita Elsa; Adkinson, N. Franklin; Grosset, Jacques; Hackman, Judith; Hamilton, Robert G.; Villarino, M. Elsa; Shang, Nong; Gordin, Fred; Khan, Awal; Hamilton, Carol Dukes; Menzies, Dick; Kerrigan, Amy; Horsburgh, C. Robert; Chaisson, Richard E.; McSherry, George; Arevalo, Bert; Vernon, Andrew; Kleinbaum, David G.; Heilig, Charles; Fryer, Kimberly; Sanchez, Isabelle; Lam, Suet K.; Scott, Nigel.

In: Clinical Infectious Diseases, Vol. 61, No. 4, 15.08.2015, p. 527-535.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Flu-like and Other Systemic Drug Reactions among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study

AU - Sterling, Timothy R.

AU - Moro, Ruth N.

AU - Borisov, Andrey S.

AU - Phillips, Elizabeth

AU - Shepherd, Gillian

AU - Adkinson, Newton Franklin

AU - Weis, Stephen

AU - Ho, Christine

AU - Villarino, Margarita Elsa

AU - Adkinson, N. Franklin

AU - Grosset, Jacques

AU - Hackman, Judith

AU - Hamilton, Robert G.

AU - Villarino, M. Elsa

AU - Shang, Nong

AU - Gordin, Fred

AU - Khan, Awal

AU - Hamilton, Carol Dukes

AU - Menzies, Dick

AU - Kerrigan, Amy

AU - Horsburgh, C. Robert

AU - Chaisson, Richard E.

AU - McSherry, George

AU - Arevalo, Bert

AU - Vernon, Andrew

AU - Kleinbaum, David G.

AU - Heilig, Charles

AU - Fryer, Kimberly

AU - Sanchez, Isabelle

AU - Lam, Suet K.

AU - Scott, Nigel

PY - 2015/8/15

Y1 - 2015/8/15

N2 - Background. Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. Methods. We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. Results. Among 7552 persons who received 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P <. 001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P =. 009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1). Conclusions. SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.

AB - Background. Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. Methods. We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. Results. Among 7552 persons who received 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P <. 001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P =. 009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1). Conclusions. SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.

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EP - 535

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