To identify the most frequently reported preferred terms （PTs） in the cases of rheumatoid arthritis （RA） patients treated with immunosuppressive biological drugs as suspected drugs, we analyzed the cases in the Japanese Adverse Drug Event Report （JADER） database. We found that pneumonia, interstitial lung disease, Pneumocystis jiroveci pneumonia （PCP), cellulitis, sepsis, and herpes zoster were the most frequently reported PTs. We obtained the reporting odds ratio （ROR） and the time to onset of these six PTs and compared them in the cases reported for each immunosuppressant as a suspected drug. We focused on RA treatment, including five tumor necrosis factor （TNF） antagonists （infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol). For pneumonia, interstitial lung disease and sepsis, no specific correlation was observed for each immunosuppressant for RA. In the case of PCP, the highest ROR was observed in the patients treated with infliximab. The time to onset of PCP in the infliximab-treated patients （median, 0.19 yr） was significantly shorter than the onset time in the patients treated with tocilizumab, an interleukin-6 receptor blocker that is another type of drug for RA（0.32 yr, p<0.01, Mann-Whitney test). The onset time in the patients treated with golimumab （0.24 yr） was also significantly shorter than the onset time for tocilizumab（p<0.05), but the ROR was not as high. These results suggested a correlation between PCP and infliximab. In the cases of cellulitis and herpes zoster, a similar correlation was observed with tocilizumab and certolizumab pegol, respectively. We should consider these results when patients have a respiratory disorder or skin/subcutaneous tissue disorder.

Objective ： Infliximab is a chimeric monoclonal antibody against tumor necrosis factor (TNF) -α that is indicated in the treatment of chronic inflammatory diseases. Infliximab is administered by intravenous infusion and may be associated with infusion related reactions (IRRs). Recent study showed that the use of concomitant antihistamines associated with an increased incidence IRR, using an observational registry database in Canada. The aim of this study was to determine whether the use of concomitant antihistamines associated with an increase in the proportional reporting ratio (PRR) of IRR, using individual case safety reports (ICSRs) with infliximab as one of the suspected drugs, not only from Canada, but also from the United States of America (US), the United Kingdom (UK), and Japan.Design ： Case-control studyMethods ： We used VigiBase, the WHO's global safety report database, in this study. One-to-one propensity-matching analysis was performed in each country using IBM SPSS version 24 to evaluate outcomes. The primary endpoint was the assessment of concomitant medications associated with IRR in the cases treated with infliximab.Results ： There were 35,729, 19,095, 4,618, and 1,565 ICSRs in which some adverse events were reported with infliximab as one of the suspected drugs in Canada, the US, the UK, and Japan, respectively, after the exclusion of ICSRs with unknown patient age or unknown patient sex. IRRs were reported in 2,293, 1,427, 303, and 69 ICSRs, respectively. The use of concomitant antihistamines was significantly associated with an increased PRR of IRR in Canada (p<0.001). The uses of concomitant antihistamines were also significantly associated with an increased PRR of IRR in the US (p<0.001), the UK (p<0.001), and Japan (p＝0.007).Conclusion ： The uses of concomitant antihistamines were associated with an increased PRR of IRR with infliximab in the case-control study using ICSRs from Canada, the US, the UK, and Japan.

To identify the most frequently reported preferred terms （PTs） in the cases of rheumatoid arthritis （RA） patients treated with immunosuppressive biological drugs as suspected drugs, we analyzed the cases in the Japanese Adverse Drug Event Report （JADER） database. We found that pneumonia, interstitial lung disease, Pneumocystis jiroveci pneumonia （PCP), cellulitis, sepsis, and herpes zoster were the most frequently reported PTs. We obtained the reporting odds ratio （ROR） and the time to onset of these six PTs and compared them in the cases reported for each immunosuppressant as a suspected drug. We focused on RA treatment, including five tumor necrosis factor （TNF） antagonists （infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol). For pneumonia, interstitial lung disease and sepsis, no specific correlation was observed for each immunosuppressant for RA. In the case of PCP, the highest ROR was observed in the patients treated with infliximab. The time to onset of PCP in the infliximab-treated patients （median, 0.19 yr） was significantly shorter than the onset time in the patients treated with tocilizumab, an interleukin-6 receptor blocker that is another type of drug for RA（0.32 yr, p<0.01, Mann-Whitney test). The onset time in the patients treated with golimumab （0.24 yr） was also significantly shorter than the onset time for tocilizumab（p<0.05), but the ROR was not as high. These results suggested a correlation between PCP and infliximab. In the cases of cellulitis and herpes zoster, a similar correlation was observed with tocilizumab and certolizumab pegol, respectively. We should consider these results when patients have a respiratory disorder or skin/subcutaneous tissue disorder.