Objective. To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor d P (TCRdP). In addition, experiments using anti-CD3 MAb were performed for comparison.Methods. CIA was induced in male DBM1 mice by immunizing them twice with bovine type I1 collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells.Results. When anti-TCRdP MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCRylS MAb had no effect on the augmented
We retrospectively observed the clinical efficacy and safety of tocilizumab (TCZ) in 74 patients with rheumatoid arthritis (RA) at 13 hospitals, without any restrictions on disease duration or stage, treatment history, and other influencing factors. TCZ was infused by the approved method, and disease activity was evaluated every 4 weeks until week 24 using a joint disease activity score (DAS28). Remission and treatment response were categorised using European League Against Rheumatism (EULAR) definitions. We also analysed the impact of previous treatment with other biologics and of concomitant methotrexate (MTX) therapy on the efficacy of TCZ. At week 24, the DAS28 had improved from 5.5 to 2.7 and the EULAR remission rate was 55.2%. Good and moderate responses according to the EULAR criteria were obtained in 61 and 36% of the patients, respectively. The biologic-naïve group had a significantly better DAS28 (2.1 vs. 2.8) and a significantly higher "good" response rate (86% vs. 54%) than the biologic-exposed group. Although the TCZ + MTX treatment group and the TCZ monotherapy group had a good response rate of 71 and 48%, respectively, the difference was not significant. Based on these results, we conclude that TCZ is able to significantly alleviate disease symptoms in a wide range of patients with RA in a normal clinical context.
We retrospectively observed the clinical efficacy and safety of tocilizumab (TCZ) in 74 patients with rheumatoid arthritis (RA) at 13 hospitals, without any restrictions on disease duration or stage, treatment history, and other influencing factors. TCZ was infused by the approved method, and disease activity was evaluated every 4 weeks until week 24 using a joint disease activity score (DAS28). Remission and treatment response were categorised using European League Against Rheumatism (EULAR) definitions. We also analysed the impact of previous treatment with other biologics and of concomitant methotrexate (MTX) therapy on the efficacy of TCZ. At week 24, the DAS28 had improved from 5.5 to 2.7 and the EULAR remission rate was 55.2%. Good and moderate responses according to the EULAR criteria were obtained in 61 and 36% of the patients, respectively. The biologic-naïve group had a significantly better DAS28 (2.1 vs. 2.8) and a significantly higher "good" response rate (86% vs. 54%) than the biologic-exposed group. Although the TCZ + MTX treatment group and the TCZ monotherapy group had a good response rate of 71 and 48%, respectively, the difference was not significant. Based on these results, we conclude that TCZ is able to significantly alleviate disease symptoms in a wide range of patients with RA in a normal clinical context.
12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.
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