A modified 3-month rifapentine plus isoniazid regimen was noninferior to a standard 9-month isoniazid regimen for preventing tuberculosis in patients with rheumatic diseases and latent infection, with a favorable safety profile and similar treatment completion, according to findings reported by Lifan Zhang, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues in eClinicalMedicine.
The researchers noted that, prior to this trial, high-level evidence for tuberculosis (TB) preventive treatment—particularly randomized controlled trials (RCTs)—remained limited globally, and clinical data on preventive treatment regimens shorter than the established 9-month isoniazid (9H) regimen —including 3-month rifapentine plus isoniazid (3HP)—were largely unavailable for this population. They wrote, “The key added value [of this study] lies in establishing high-level (RCT) evidence for a viable alternative. The modified regimen was designed to mitigate potential risks in this high-risk population….”
“This regimen might be more suitable in patients with underlying diseases and those on concomitant medications,” they added.
Study Details
The trial enrolled 536 patients aged 18 to 70 years with high-risk rheumatic diseases and latent TB infection who were receiving immunosuppressive therapy at 9 tertiary general hospitals in China. Participants were randomly assigned in a 1:1 ratio to receive either a modified 3HP preventive treatment (3HP-PUMCH) regimen, consisting of twice-weekly rifapentine (450 mg; 900 mg/week) plus daily isoniazid (up to 300 mg/day), or the 9H regimen of daily isoniazid (300 mg).
The primary endpoint was occurrence of TB, with a prespecified noninferiority margin of 1.4 percentage points. Analyses were conducted in the modified intention-to-treat population.
Follow-up data were provided for approximately 2 years.
Key Findings
Among 509 patients (3HP-PUMCH: 249; 9H: 260) included in the analysis, the cumulative rate of TB was 0% in the 3HP-PUMCH group compared with 1.2% in the 9H group.
Drug discontinuation due to serious adverse events or TB occurrence was reported in 2.8% of patients treated with 3HP-PUMCH and 1.9% of those who received 9H. Adverse drug reactions occurred in 9.6% of the 3HP-PUMCH group vs 15% of the 9H group. Hepatotoxicity was observed in 4.4% vs 10.4%, respectively—a statistically significant difference.
Treatment completion was achieved in 89.6% of patients administered 3HP-PUMCH and 91.2% of those who received 9H.
Insights and Opportunities
Several limitations were noted, including the lack of pharmacokinetic and pharmacogenomic data, limited subgroup analyses due to the small sample size and low number of events, and incomplete capture of comorbidities and concomitant medications. The researchers also reported that the lower event rate reduced certainty and limited conclusions beyond noninferiority, that the COVID-19 pandemic may have affected TB exposure and reporting, and that long-term efficacy remains unclear and findings may not be generalizable beyond patients with high-risk rheumatic diseases or to those managed in primary care settings.
The researchers concluded, “Our findings offer important initial data that may influence clinical practice and policy discussions. This short-course preventive treatment option presents a promising alternative to the standard 9H regimen, reducing the treatment burden and drug toxicity, which are significant barriers to successful TB prevention in this population. While acknowledging the limitations…, our findings represent high-level evidence that supports considering short-course TB preventive treatment in [patients with] rheumatic diseases.”
Looking ahead, they wrote that further large-scale trials are needed to confirm these results across diverse settings and to inform updates to international guidelines.
Disclosure: The researchers reported no conflicts of interest.
Funding: National Natural Science Foundation of China.
Source: eClinicalMedicine