ObjectiveKnowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting.MethodsWe used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders.ResultsA total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6–8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78–3.04) for infliximab, 1.72 (0.88–3.34) for adalimumab, 1.11 (0.55–2.21) for abatacept, and 1.02 (0.55–1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1–5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72–11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection.ConclusionsThe magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use.

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Objective. To investigate the response to and safety of anti-tumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)-positive patients with rheumatoid arthritis (RA).Methods. Therapeutic response was evaluated in 10 HTLV-I-positive and 20 HTLV-I-negative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. Results. Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.0003). The response rate to anti-TNF therapy was lower in HTLV-I-positive patients than in HTLV-I-negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-I-positive patients were significantly higher than in HTLV-Inegative patients (P ‫؍‬ 0.003, P ‫؍‬ 0.03, and P ‫؍‬ 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.013). During the 2-year observation period, no patients developed ATL. Conclusion. These data suggest that HTLV-I-positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-I-negative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.

ABSTRACT. The effects of mycotoxins on mitogen-stimulated proliferation of bovine peripheral blood mononuclear cells (PBMCs) were investigated. Aflatoxin B 1 (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN) were added to cultures of PBMCs, and the proliferation responses were measured using MTT bioassays. Suppression of the proliferation of calf PBMCs by AFB 1 and DON was significantly stronger than that of cow PBMCs, whereas there were no differences in suppressive effects on PBMCs from Holstein and Japanese Black calves and cows. The suppressive effect was greatest in the order of DON, AFB 1 and ZEN, and the effects of DON and AFB 1 seemed to be dose-dependent. The results suggest that some mycotoxins directly suppress proliferation of bovine PBMCs. KEY WORDS: bovine, mononuclear cell, mycotoxin.J. Vet. Med. Sci. 70(2): 193-196, 2008 Mycotoxin is a general term for harmful substances produced by certain fungi. In Japan, there are permissible concentrations of the mycotoxins aflatoxin B 1 (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN) in feed for animals. There have been many studies on the effects of mycotoxins on the immune functions of various animals [1][2][3][4][5][6][7][8][9][10][11][12]15]. We previously conducted blood profile tests for cows on dairy farms that were given feed contaminated with mycotoxins (mainly AFB 1 ) and found reduced levels of T cells in many cows [14]. These findings indicate that mycotoxins may induce immune suppression, particularly suppression of bovine T-lymphocyte function. However, the relationships between the direct effect of a mycotoxin on bovine peripheral blood mononuclear cells (PBMCs) and age or breed has not been elucidated. Moreover, there have been only a few studies in which the effects of various mycotoxins were examined [4,5]. The aim of this study was therefore to clarify the effects of AFB1, DON and ZEN on proliferation of bovine PBMCs.The cattle tested were clinically healthy Holstein cows (n=6), Japanese Black cows (n=6), Holstein calves (n=6, =1, =5) and Japanese Black calves (n=6, =3, =3). The cows were between 3 and 7 years old, and the calves were between 1 and 2 months old. Aflatoxin B 1 from Aspergillus flavus (AFB 1 ), deoxynivalenol (DON) and zearalenone (ZEN; Sigma-Aldrich Co., St. Louis, MO, U.S.A.) were used as mycotoxin reagents.Blood was collected from each animal into sampling tubes containing heparin. Each 5 ml blood sample was diluted with 5 ml 1/15M PBS (pH #7.4) and laid on 4.5 ml Lymphocepar I (Immuno-Biological Laboratories Co., Ltd. Gunma, Japan). PBMCs were isolated by centrifugation (1,500 rpm, 60 min) and washed several times with PBS. The samples were seeded into 96-well microplates at 1 × 10 6 cells/well and diluted with 10% FCS-containing RPMI Medium 1640 (Gibco BRL, Gaithersburg, MD, U.S.A.) at a final volume of 200 µl/well. Ten µg/ml of phytohaemagglutin-P (PHA-P; Sigma-Aldrich Co.) was added to each PBMC culture, and then each culture was mixed with AFB 1 , DON, ZEN, AFB 1 +DON, AFB 1 +ZEN or DON+ZEN and incubated f...

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