Influenza-like reactions to latent TB treatment not mediated by drug antibodies
In patients with latent tuberculosis, influenza-like reactions following treatment with isoniazid plus rifapentine or isoniazid alone were not associated with the presence of antibodies against isoniazid, rifapentine, and rifapentine metabolite.
Influenza-like reactions in patients with latent tuberculosis (TB) infection receiving weekly isoniazid plus rifapentine for 3 months (3HP) or daily isoniazid for 9 months (9H) were not found to be mediated by the presence of drug antibodies, according to findings published in The Journal of Infectious Diseases.
Previous research suggests that antibody reactions to TB treatments may be responsible for influenza-like reactions, defined as grade 2, 3, or 4 adverse events involving influenza-related symptoms, with the exception of hepatotoxicity.
In a substudy nested within a multicenter, open-label, randomized phase 3 trial, researchers evaluated study patients (N=128) with latent TB infection who experienced influenza-like reactions following treatment with 3HP or 9H. The researchers assessed patients for the presence of antibodies against rifapentine, isoniazid, rifampin, and rifapentine metabolite. They also determined whether these antibodies occur more frequently in patients with vs without (controls) influenza-like reactions during or after latent TB treatment.
Among 69 patients in the 3HP group and 59 in the 9H group, 22 and 12 developed influenza-like reactions, respectively. Compared with control patients (n=47 in each group), 3HP and 9H recipients who experienced influenza-like reactions received fewer treatment doses (median, 5 vs 12 and 54 vs 264, respectively) and had shorter durations of drug exposure (median, 29 vs 83 days and 59 vs 286 days, respectively).
In the 3HP group, the percentage of patients with immunoglobulin (Ig) G or IgM antibodies against isoniazid, rifampin, and rifapentine did not significantly differ between those with vs without influenza-like reactions:
- Anti-isoniazid antibodies: IgG (9% vs 9%; P =.9); IgM (0% vs 9%)
- Anti-rifampin antibodies: IgG (0% vs 2%); IgM (5% vs 9%)
- Anti-rifapentine antibodies: IgG (9% vs 13%; P =.7); IgM (0% vs 4%)
- Anti-rifapentine metabolite antibodies: IgG (0% vs 4%; P =.9); IgM (0% vs 13%)
Among 9H recipients, none of those who developed influenza-like reactions tested positive for any antibodies, whereas 2%, 9%, 6%, and 2% of control patients tested positive for anti-rifapentine IgM, anti-isoniazid IgG and IgM, anti-rifampin IgM, and anti-rifapentine metabolite IgM antibodies, respectively.
The researchers noted that some serum samples were not collected from patients who experienced influenza-like reactions at the time of the event. Other limitations include insufficient power to confirm the negative association between the development of influenza-like reactions and presence of drug antibodies, as well as the lack of baseline serum samples from some control patients in both treatment groups.
According to the researchers, “We detected anti-rifapentine, anti-isoniazid, anti-rifampin, and anti-rifapentine metabolite antibodies, but the proportions of participants with antibodies were low, and not different in participants with flu-like reactions or controls.”
Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
References:
Moro RN, Mehaffy C, De P, et al. Assessment for antibodies to rifapentine and isoniazid in persons developing flu-like reactions during treatment of latent tuberculosis infection. J Infect Dis. Published online April 19, 2024. doi:10.1093/infdis/jiae180
Source: Infectious Disease Advisor
