Adjunctive vitamin D in tuberculosis treatment

meta-analysis of individual participant data

David A. Jolliffe, Davaasambuu Ganmaa, Christian Wejse, Rubhana Raqib, M. Ahsanul Haq, Nawal Salahuddin, Peter K. Daley, Anna P. Ralph, Thomas R. Ziegler, Adrian R. Martineau

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation.

    Methods: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype.

    Results: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes.

    Conclusions: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

    Original languageEnglish
    Article number1802003
    JournalThe European respiratory journal
    Volume53
    Issue number3
    Early online date7 Mar 2019
    DOIs
    Publication statusPublished - Mar 2019

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    Sputum
    Vitamin D
    Meta-Analysis
    Tuberculosis
    Pulmonary Tuberculosis
    Multidrug-Resistant Tuberculosis
    Therapeutics
    Randomized Controlled Trials
    Calcitriol Receptors
    Isoniazid
    Rifampin
    Genotype
    HIV
    Weights and Measures
    Incidence
    Pharmaceutical Preparations

    Cite this

    Jolliffe, D. A., Ganmaa, D., Wejse, C., Raqib, R., Haq, M. A., Salahuddin, N., ... Martineau, A. R. (2019). Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data. The European respiratory journal, 53(3), [1802003]. https://doi.org/10.1183/13993003.02003-2018
    Jolliffe, David A. ; Ganmaa, Davaasambuu ; Wejse, Christian ; Raqib, Rubhana ; Haq, M. Ahsanul ; Salahuddin, Nawal ; Daley, Peter K. ; Ralph, Anna P. ; Ziegler, Thomas R. ; Martineau, Adrian R. / Adjunctive vitamin D in tuberculosis treatment : meta-analysis of individual participant data. In: The European respiratory journal. 2019 ; Vol. 53, No. 3.
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    title = "Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data",
    abstract = "Background: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. Methods: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. Results: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95{\%} CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95{\%} CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95{\%} CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95{\%} CI 1.01-1.31), but did not influence other secondary outcomes. Conclusions: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.",
    author = "Jolliffe, {David A.} and Davaasambuu Ganmaa and Christian Wejse and Rubhana Raqib and Haq, {M. Ahsanul} and Nawal Salahuddin and Daley, {Peter K.} and Ralph, {Anna P.} and Ziegler, {Thomas R.} and Martineau, {Adrian R.}",
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    Jolliffe, DA, Ganmaa, D, Wejse, C, Raqib, R, Haq, MA, Salahuddin, N, Daley, PK, Ralph, AP, Ziegler, TR & Martineau, AR 2019, 'Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data', The European respiratory journal, vol. 53, no. 3, 1802003. https://doi.org/10.1183/13993003.02003-2018

    Adjunctive vitamin D in tuberculosis treatment : meta-analysis of individual participant data. / Jolliffe, David A.; Ganmaa, Davaasambuu; Wejse, Christian; Raqib, Rubhana; Haq, M. Ahsanul; Salahuddin, Nawal; Daley, Peter K.; Ralph, Anna P.; Ziegler, Thomas R.; Martineau, Adrian R.

    In: The European respiratory journal, Vol. 53, No. 3, 1802003, 03.2019.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Adjunctive vitamin D in tuberculosis treatment

    T2 - meta-analysis of individual participant data

    AU - Jolliffe, David A.

    AU - Ganmaa, Davaasambuu

    AU - Wejse, Christian

    AU - Raqib, Rubhana

    AU - Haq, M. Ahsanul

    AU - Salahuddin, Nawal

    AU - Daley, Peter K.

    AU - Ralph, Anna P.

    AU - Ziegler, Thomas R.

    AU - Martineau, Adrian R.

    PY - 2019/3

    Y1 - 2019/3

    N2 - Background: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. Methods: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. Results: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. Conclusions: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

    AB - Background: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. Methods: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. Results: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. Conclusions: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

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    U2 - 10.1183/13993003.02003-2018

    DO - 10.1183/13993003.02003-2018

    M3 - Article

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    JO - European Respiratory Journal

    JF - European Respiratory Journal

    SN - 0903-1936

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