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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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.",
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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

VL - 53

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

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