Toxicity associated with tuberculosis chemotherapy in the REMoxTB study

Simple item page
dc.contributor.authorTweed, Conor D
dc.contributor.authorCrook, Angela M
dc.contributor.authorAmukoye, Evans I
dc.contributor.authorDawson, Rodney
dc.contributor.authorDiacon, Andreas H
dc.contributor.authorHanekom, Madeline
dc.contributor.authorMcHugh, Timothy D
dc.contributor.authorMendel, Carl M
dc.contributor.authorMeredith, Sarah K
dc.contributor.authorMurphy, Michael E
dc.contributor.authorMurthy, Saraswathi E
dc.contributor.authorNunn, Andrew J
dc.contributor.authorPhillips, Patrick P J
dc.contributor.authorSingh, Kasha P
dc.contributor.authorSpigelman, Melvin
dc.contributor.authorWills, Genevieve H
dc.contributor.authorGillespie, Stephen H
dc.date.accessioned2018-07-16T13:01:53Z
dc.date.available2018-07-16T13:01:53Z
dc.date.issued2018-07-11
dc.date.updated2018-07-15T03:27:08Z
dc.description.abstractAbstract Background The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. Methods All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. Results In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms (“isoniazid arm” with moxifloxacin substituted for ethambutol & “ethambutol arm” with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91–1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55–7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59–6.10, p < 0.001). Conclusions Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.
dc.identifier.apacitationTweed, C. D., Crook, A. M., Amukoye, E. I., Dawson, R., Diacon, A. H., Hanekom, M., ... Gillespie, S. H. (2018). Toxicity associated with tuberculosis chemotherapy in the REMoxTB study. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/28300en_ZA
dc.identifier.chicagocitationTweed, Conor D, Angela M Crook, Evans I Amukoye, Rodney Dawson, Andreas H Diacon, Madeline Hanekom, Timothy D McHugh, et al "Toxicity associated with tuberculosis chemotherapy in the REMoxTB study." <i>BMC Infectious Diseases</i> (2018) http://hdl.handle.net/11427/28300en_ZA
dc.identifier.citationBMC Infectious Diseases. 2018 Jul 11;18(1):317
dc.identifier.ris TY - Journal Article AU - Tweed, Conor D AU - Crook, Angela M AU - Amukoye, Evans I AU - Dawson, Rodney AU - Diacon, Andreas H AU - Hanekom, Madeline AU - McHugh, Timothy D AU - Mendel, Carl M AU - Meredith, Sarah K AU - Murphy, Michael E AU - Murthy, Saraswathi E AU - Nunn, Andrew J AU - Phillips, Patrick P J AU - Singh, Kasha P AU - Spigelman, Melvin AU - Wills, Genevieve H AU - Gillespie, Stephen H AB - Abstract Background The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. Methods All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. Results In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms (“isoniazid arm” with moxifloxacin substituted for ethambutol & “ethambutol arm” with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91–1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55–7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59–6.10, p < 0.001). Conclusions Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring. DA - 2018-07-11 DB - OpenUCT DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Toxicity associated with tuberculosis chemotherapy in the REMoxTB study TI - Toxicity associated with tuberculosis chemotherapy in the REMoxTB study UR - http://hdl.handle.net/11427/28300 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12879-018-3230-6
dc.identifier.urihttp://hdl.handle.net/11427/28300
dc.identifier.vancouvercitationTweed CD, Crook AM, Amukoye EI, Dawson R, Diacon AH, Hanekom M, et al. Toxicity associated with tuberculosis chemotherapy in the REMoxTB study. BMC Infectious Diseases. 2018; http://hdl.handle.net/11427/28300.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceBMC Infectious Diseases
dc.source.urihttps://bmcinfectdis.biomedcentral.com/
dc.subject.otherTuberculosis
dc.subject.otherToxicity
dc.subject.otherClinical trials
dc.subject.otherAdverse events
dc.titleToxicity associated with tuberculosis chemotherapy in the REMoxTB study
dc.typeJournal Article
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Tweed_2018_Article.pdf
Size:
719.43 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.72 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles