A combined statistical analysis based on the active pharmacovigilance and disproportionality assessment for the safety of fluoroquinolones in shorter treatment of rifampicin-resistant tuberculosis.

Most treatment regimens for rifampicin-resistant tuberculosis include fluoroquinolones. The clinical effectiveness and generally favorable safety profiles of fluoroquinolones have been highlighted in earlier articles. The current paper is focused on the risks and benefits of fluoroquinolones used in anti-tuberculosis treatment in Armenia. In total, 211 patients were engaged in this research. Systemic and detailed collection of data on adverse events was conducted according to the principles of active pharmacovigilance. The safety data were assessed based on the disproportionality analysis. The most common adverse event observed among the patients exposed to fluoroquinolone-based regimens was arthralgia (16.6%, 95% CI 11.6-21.6). All cases of arthralgia resolved after replacement of levofloxacin with moxifloxacin. The rate of arthralgia was significantly higher in the patients treated with standard shorter regimens compared with the population exposed to longer individual fluoroquinolone-based regimens. The disproportion in reporting of arthralgia was observed among the patients exposed to the mSTRs compared with other regimens. The assessment of the association between arthralgia and body mass among the patients treated with individual longer regimens revealed that the patients weighing less than 69 kg were at five times higher risk of developing arthralgia. Other unfavorable events (allergy, QT interval prolongation, drug-resistance amplification) were observed at a relatively low frequency. The combination of active pharmacovigilance with disproportionality analysis could be used to supplement the safety data on anti-tuberculosis regimens. The rational management of fluoroquinolone-induced adverse events minimizes their impact on the effectiveness of treatment for rifampicin-resistant tuberculosis.