Rifamycin-containing regimens appear effective, well tolerated for preventing latent TB reactivation

At least 3 months of therapy with rifamycin-containing regimens was reasonably well tolerated, efficacious, and possibly better than isoniazid (INH) monotherapy for preventing patients with latent tuberculosis (TB) infection from developing active cases in countries with a low TB incidence, a meta-analysis concluded.

Researchers did a meta-analysis of 53 trials to address the benefits and harms of 15 regimens aimed at preventing active TB in patients with latent infections. Treatments considered to be clinically similar were grouped for analysis: all isoniazid (INH)-rifampicin (RMP) regimens, INH regimens 3 to 4 months in duration, INH regimens 12 months or more in duration, INH-RMP regimens 3 to 4 months in duration, all RMP-pyrazinamide (PZA) regimens, and all RMP-INH-PZA regimens. Results appeared online first Aug. 12 in Annals of Internal Medicine.

The researchers concluded that regimens of INH only for 6 or 12 to 72 months, RMP only, RMP-INH for 3 to 4 months, RMP-INH-PZA, and RMP-PZA were efficacious for preventing active TB. Odds ratios (ORs) and 95% credible intervals (95% CrI) were calculated for all 15 regimens versus placebo. Compared with placebo, the odds ratios for active infection were:

• INH for 6 months (OR, 0.64; 95% CrI, 0.48 to 0.83),
• INH for 12 months or longer (OR, 0.52; 95% CrI, 0.41 to 0.66)
• RMP for 3 to 4 months (OR, 0.41; 95% CrI, 0.18 to 0.86),
• Rifapentine (RPT)-INH (OR, 0.61; 95% CrI, 0.29 to 1.22), and
• RMP-INH (OR, 0.52; 95% CrI, 0.34 to 0.79).

Because currently recommended regimens are efficacious when studied in various settings and patient populations, the focus of clinical decision making shifts to considering potential adverse events (AEs) and interactions for each patient, the authors suggested. They added that global elimination of TB depends on shorter, effective, and well-tolerated regimens for latent infections.

“The long half-life of RPT is a key factor in making weekly INH-RPT noninferior to the current standard of care,” they wrote. “Even shorter regimens may be feasible with other anti-TB drugs that also have a long half-life, such as bedaquiline, assuming its AE profile is similar to existing TB drugs.”

An accompanying editorial said the study provides clear evidence that it is time to move away from INH as a primary therapy for latent TB and toward rifamycin-containing regimens that work better, are safer, and have shorter treatment durations.

“Surely, it is time to get a move on—away from INH as our primary therapy and toward regimens containing rifamycin,” the editorial states. “The advantages are considerable for patients who would benefit from greater safety and better protection against TB and TB programs in which shorter duration should result in reduced workload and potentially lower costs.”