Rifampicin may be safer than isoniazid in latent TB treatment

Latent TB infection affects approximately 25% of the world’s population. Daily isoniazid for 6 to 9 months is the most common regimen used globally for this indication. However, adverse events with isoniazid is a concern that significantly limits treatment of latent TB infection. Additionally, age-related hepatotoxicity and the long treatment duration result in suboptimal completion and adherence of the isoniazid regimen. Comparatively, 4 months of daily rifampicin has consistently shown better completion, reduced toxicity, and noninferior effectiveness to isoniazid among numerous studies. However, timing and risk factors of the adverse events were not formally evaluated.

Therefore, this study conducted a post-hoc safety analysis that combined populations from phase 2 and phase 3 open-label, randomized controlled trials, to establish risk factors for adverse events during latent TB treatment (ClinicalTrials.gov Identifiers: NCT00170209 and NCT00931736, respectively).

The safety populations from each trial comprised consenting adults who had a positive latent TB infection diagnostic test and indication for treatment, without contraindications to rifampicin or isoniazid. The primary outcome evaluated adverse events (presence/reports of a grade £2 rash and all events grade ³3) that resulted in permanent study drug discontinuation and judged to be possibly or probably related to the study drug by an independent, masked, 3-member adjudication panel. Participants were randomly assigned to 1 of 2 treatment groups: 3205 participants received isoniazid and 3280 participants received rifampicin.

Results suggested that rifampicin was safer than isoniazid and adverse events were not associated with older age. Compared with participants who received rifampicin (50 [1.5%] participants), participants who received isoniazid experienced more grade £ 2 rashes or any grade ³3 events (86 [2.7%] participants) (risk difference, -1.2%). With isoniazid treatment, adverse events were associated with age; compared with individuals aged 18 to 34 years, the adjusted odd ratio (aOR) for adverse events was 1.8 for individuals aged 35 to 64 years and 3.0 for individuals aged 65 to 90 years. With rifampicin treatment, adverse events were associated with inconsistent medication adherence but not age (aOR, 1.1 for individuals aged 35-64 years and aOR, 1.7 for individuals aged 65-90 years).

Overall, the study authors concluded that, “On the basis of safety considerations alone, rifampicin should become a primary treatment option for latent tuberculosis infection.”

Reference

Campbell JR, Trajman A, Cook VJ, et al. Adverse events in adults with latent tuberculosis infection receiving daily rifampicin or isoniazid: post-hoc safety analysis of two randomized controlled trials [published online December 19, 2019]. Lancet Infect Dis. doi: 10.1016/S1473-3099(19)30575-4

Source: Infectious Disease Advisor