トファシチニブ治療関節リウマチ患者における 結核, B型肝炎および帯状疱疹
Immunotherapy. 2019 Mar;11(4):321-333.The risk of TB and hepatitis B virus (HBV) appears to be no greater with TOF than with bDMARDs. Most cases of TB during TOF studies occurred in regions with high background rate of TB, including east Asian countries. TOF is also associated with a higher rate of herpes zoster (HZ) compared with bDMARDs. DMARDs used to treat RA can increase the risk of infections by causing a degree of immunosuppression. A range of bacterial and viral infections have been observed in association with DMARD therapy, with TB, HBV and HZ reactivation being the most common. This review summarizes the prevalence of TB, HBV and HZ in RA patients treated with TOF, focusing on east Asian countries.An integrated analysis of global data from Phase I-III and LTE studies with TOF 5 or 10 mg BD, found an overall TB IR of 0.2, with higher rates in TOF 10 mg (0.3 per 100 PY) compared to TOF 5 mg (0.08 per 100 PY). Little information is available about the risk of HBV reactivation during TOF treatment. A meta-analysis of 14 studies involving patients treated with any DMARD found an HBV reactivation rate of 0.0042. Real-world data from US health plans indicated that incidence of HZ in more than 8000 TOF users was approximately 4% per year, with doubled incidence in concomitant glucocorticoid use. The IR for HZ was also higher in Asia compared to other regions, especially Japan/Korea. Along with most TB cases during TOF studies occurring in regions with high background rate of TB, and comparatively rare in areas with low or intermediate background rates.Higher rates of HZ with TOF treatment is observed compared to bDMARDs, although they are considered manageable. Asian countries such as China have a high background rate of TB and HBV. Thus, country-specific strategy for screening and managing infections in patients undergoing treatment with tsDMARDs such as TOF and bDMARDs may be appropriate.