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Title: Toxicity related to the treatment of pulmonary tuberculosis
Author: Tweed, Conor Duncan
ISNI:       0000 0004 7965 1331
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Introduction: The incidence and nature of toxicity related to tuberculosis (TB) treatment, who is most commonly affected and what is the true impact on treatment is predominantly characterised through retrospective or observational studies; with varying definitions for toxicity and estimates of the incidence or patient groups at highest risk. REMoxTB was a randomised, controlled, phase III pulmonary TB clinical trial with stringent collection of efficacy and safety data. Methods: A total of 639 patients received standard TB therapy as a control arm for the trial, with 655 patients and 636 patients allocated to the "isoniazid" and "ethambutol" arms. Related grade 3 and 4 adverse events were used to investigate the general toxicity observed during treatment and the liver biochemical tests collected were described in detail separately. Regression techniques investigated the association between patient demographics and toxicity. Lastly, the incidence of adverse events and the longitudinal pattern of clinical and laboratory data was described for HIV positive patients. Results: Approximately 10% of patients experienced clinically significant toxicity attributed to their drug therapy. Older patients, female patients, those of Asian ethnicity, and HIV positive patients were at the greatest risk for toxicity. Significant drug toxicity most commonly occurred in the first two months of treatment. Liver dysfunction was the most frequent clinically significant toxicity. Patients who experienced one or more episode of clinically significant toxicity were at higher risk of failing treatment. Those receiving the experimental moxifloxacin-containing arms experienced lower rates of clinically significant toxicity. Conclusions: This work identifies patient groups who are at higher risk of toxicity, when this toxicity is likely to occur, and what form it most commonly takes: informing the allocation of often limited resources to appropriately monitor those patients who are at greatest risk during treatment. Additionally, by demonstrating a higher risk of failing treatment associated with drug toxicity, this work also provides further justification for changes at the policy level. Finally, the experimental arms could have a place in the management of patients at high risk of toxicity but this must be viewed in light of uncertainty surrounding the optimal duration of therapy.
Supervisor: Meredith, S. ; McHugh, T. ; Crook, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available