Month 2 culture status and treatment duration as predictors of tuberculosis relapse risk in a meta-regression model.
BACKGROUND
New drugs and regimens with the potential to transform tuberculosis treatment are presently in early stage clinical trials.


OBJECTIVE
The goal of the present study was to infer the required duration of these treatments.


METHODS
A meta-regression model was developed to predict relapse risk using treatment duration and month 2 sputum culture positive rate as predictors, based on published historical data from 24 studies describing 58 regimens in 7793 patients. Regimens in which rifampin was administered for the first 2 months but not subsequently were excluded. The model treated study as a random effect.


RESULTS
The model predicted that new regimens of 4 or 5 months duration with rates of culture positivity after 2 months of 1% or 3%, would yield relapse rates of 4.0% or 4.1%, respectively. In both cases, the upper limit of the 2-sided 80% prediction interval for relapse for a hypothetical trial with 680 subjects per arm was <10%. Analysis using this model of published month 2 data for moxifloxacin-containing regimens indicated they would result in relapse rates similar to standard therapy only if administered for ≥5 months.


CONCLUSIONS
This model is proposed to inform the required duration of treatment of new TB regimens, potentially hastening their accelerated approval by several years.
Specialty Care, Pfizer, Groton, Connecticut, United States of America. rswallis@gmail.com
Robert S
RS
Wallis
Cunshan
C
Wang
Daniel
D
Meyer
Neal
N
Thomas
D005500:Follow-Up Studies; D006801:Humans; D015201:Meta-Analysis as Topic; D008828:Microbiological Techniques; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011379:Prognosis; D011718:Pyrazinamide / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D012044:Regression Analysis; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D013183:Sputum / Q000166:cytology / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D011718:Pyrazinamide; D012293:Rifampin