Treatment with high-dose rifamycin (HDR)-based regimens was not associated with an increased risk for severe adverse events (SAE) compared with standard-dose rifamycin (SDR)-based regimens among patients with tuberculosis (TB) infection, according to results of a study published in Thorax.
Investigators performed a systemic review and meta-analysis of studies published between 1965 and 2021 that compared the effect of daily treatment with HDR-based regimens vs SDR-based regimens in patients with TB infection. All studies included in the analysis were randomized controlled trials. The primary outcome was the pooled rate of SAEs per person-year (PY) of exposure; secondary outcomes included death, adverse events of any severity, SAEs by organ, efficacy outcomes of 2-month culture conversion, trial withdrawal, and relapse.
Overall, 13 studies were analyzed, representing a total of 6168 participants with active TB infection and 7930 PY of follow-up. Among participants enrolled across all included studies, 3535 received HDR-based regimens with 4387 PY of follow-up and 2633 received SDR-based regimens with 3543 PY of follow-up. Among all 13 studies included, 10 enrolled participants infected with pulmonary TB and 3 enrolled participants infected with TB meningitis.
Among a total of 3217 adverse events reported in the included studies, 1464 (46%) were SAEs. The investigators found no significant differences in the pooled incidence rate ratio (IRR) of SAEs between patients who received HDR-based regimens vs those who received SDR-based regimens (IRR, 1.00; 95% CI, 0.82-1.23; I2 =41%). There were also no significant differences observed between patients included in both treatment groups when the analysis was limited to only SAEs that the investigators’ noted as “possibly, probably, or likely medication-related” (IRR, 1.07; 95% CI, 0.82-1.41; I2 =0%). Results from other studies included in the analysis that also showed no significant difference in the pooled SAE rate included those with a decreased risk of bias (IRR, 0.98; 95% CI, 0.79-1.20; I2 =44%), and those that assessed treatment with rifampicin (IRR, 1.00; 95% CI, 0.75–1.32; I2 =38%). Analysis of pooled secondary outcomes, including death (risk ratio [RR], 0.89; 95% CI, 0.74-1.06; I2 =0%), 2-month culture conversion (RR, 1.14; 95% CI, 0.96-1.36; I2 =85%), relapse (RR, 1.06; 95% CI, 0.37-3.07; I2 =41%), and study withdrawal (IRR, 0.86; 95% CI, 0.68-1.09; I2 =0[WU1] %) also showed no significant differences.
Limitations included heterogeneity, and several studies included in the analysis had a small sample size. In addition, several studies had relatively few SAEs, differing definitions of both SAE and culture conversion, and no standard protocol for reporting adverse events.
According to the investigators, “with numerous ongoing and unpublished studies examining high-dose rifampicin, we expect to further our understanding of appropriate rifamycin dosing and better identify populations that stand to benefit most from HDR in the coming years.”
Arbiv OA, Kim JM, Yan M, et al. High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis. Thorax. Published online January 7, 2022. doi: 10.1136/thoraxjnl-2020-216497