Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis

Kitahara, Koichi; Kawai, Shinichi

doi:10.1097/bor.0b013e328099af80

Cited by 105 publications

(55 citation statements)

References 52 publications

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“…Live vaccine, CyA, bosentan, and potassium-sparing diuretics are prohibited to use concomitant with TAC. Furthermore, we should be also careful to use TAC with following drugs such as macrolides, antifungal azoles, some of calcium channel blockers because of possibility of increase in blood concentration [16,22,23,41]. A lower incidence of adverse events than in past clinical reports may be due to an appropriate and Xexible dose regimen.…”

Section: Discussionmentioning

confidence: 92%

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

et al. 2010

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The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus (TAC) in various manifestations of systemic lupus erythematosus (SLE) patients in daily clinical practice. Each of the 21 TAC-treated patients with SLE in our care over 2 years was enrolled in this open-label trial. Patients were administered TAC at a dosage of 1-6 mg once daily, followed up for 24 weeks. Efficacy and safety were evaluated utilizing clinical and laboratory findings. As treatment targets, TAC was preferentially used with oral corticosteroid administration for mild active manifestations such as arthritis, skin eruptions, or asymptomatic nephritis. In efficacy, the mean value of the SLE disease activity index was significantly reduced to 4.1, 2.7, 1.8, and 1.2 (N=21, 20, 16 and 13) at 0, 4, 12, and 24 weeks, respectively. In eight cases, treatment was discontinued within 24 weeks due to insufficient effects (6 cases) and side effects (2 cases). Non-serious side effects were observed in only five cases (23.8%) over 24 weeks. TAC can be considered both effective and safe for the treatment of various manifestations of SLE.

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Section: Discussionmentioning

confidence: 92%

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

et al. 2010

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“…This conclusion also has interesting implications for the action of CsA. This immunosuppressive drug is successfully used in the treatment of RA (Kitahara and Kawai, 2007). However, the anti-inflammatory effect of CsA cannot be sufficiently explained by its immunosuppressive function.…”

Section: Interaction Of Stat3 With Cyclophilin B K Bauer Et Almentioning

confidence: 94%

Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells

et al. 2009

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Signal transducer and activator of transcription 3 (Stat3) is the major mediator of interleukin-6 (IL-6) family cytokines. In addition, Stat3 is known to be involved in the pathophysiology of many malignancies. Here, we show that the cis-trans peptidyl-prolyl isomerase cyclophilin (Cyp) B specifically interacts with Stat3, whereas the highly related CypA does not. CypB knockdown inhibited the IL-6-induced transactivation potential but not the tyrosine phosphorylation of Stat3. Binding of CypB to Stat3 target promoters and alteration of the intranuclear localization of Stat3 on CypB depletion suggested a nuclear function of Stat3/CypB interaction. By contrast, CypA knockdown inhibited Stat3 IL-6-induced tyrosine phosphorylation and nuclear translocation. The Cyp inhibitor cyclosporine A (CsA) caused similar effects. However, Stat1 activation in response to IL-6 or interferon-c was not affected by Cyp silencing or CsA treatment. As a result, Cyp knockdown shifted IL-6 signaling to a Stat1-dominated pathway. Furthermore, Cyp depletion or treatment with CsA induced apoptosis in IL-6-dependent multiple myeloma cells, whereas an IL-6-independent line was not affected. Thus, Cyps support the anti-apoptotic action of Stat3. Taken together, CypA and CypB both play pivotal roles, yet at different signaling levels, for Stat3 activation and function. These data also suggest a novel mechanism of CsA action.

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“…It is used to control rejection after kidney, liver, heart, and bone marrow transplantation, and is also used to control graftversus-host disease. In Japan, tacrolimus is additionally employed to treat myasthenia gravis [13,14], rheumatoid arthritis [15], and atopic dermatitis (as a topical preparation) [16]. Regarding the efficacy of tacrolimus for lupus nephritis, it has been shown to prolong survival and decrease proteinuria in murine models of SLE (MRL/lpr mice and NZB/NZWF1 mice) [17].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

2009

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We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 +/- 31.0% (mean +/- SD) in the tacrolimus group (n = 28) and was increased by 2.3 +/- 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.

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Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis

Cited by 105 publications

References 52 publications

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

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