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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Cyclosporine A and FK506 are fungal metabolites. These two drugs have a relatively selective effect on helper T lymphocytes. They block T cell proliferation by reducing the expression of several cytokine genes, those which rely on activation of the gene by a particular transcription factor. Included in this group of cytokines are interleukin-2, interleukin-4, and tumor neucrosis factor-a. Both Th1 and Th2 helper T cells are affected, and thus, both cellular and humoral immune responses are reduced. However, Cyclosporine A and FK506 interfere only with acute rejection responses and are not effective at all for treatment of chronic rejection. A disadvantage of these two drugs is that they do not stop immune responses once they have begun. Cyclosporine A also has a number of undesirable side effects, including toxic effects on the kidneys and liver. FK506 has fewer side effects, but those it has are similar to those listed above for Cyclosporine A. Both drugs, because they cannot be synthetically made, are very expensive.
Non-Melanoma Skin Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Irene De Francesco, Sean Whittaker, Stephen L. Morris
Small cohort studies have reported that interleukin-12 (IL-12) and IFN-α can produce clinical responses, but their role remains to be established. Cyclosporine is contraindicated, as it may cause disease progression.242,243
Medical Treatment of Vanishing Bile Duct Syndrome in Adults
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
C. Squarcia Giussani, Andrea Crosignani, Mauro Podda
The efficacy of cyclosporine has been evaluated in three double-blind controlled studies.71–73 The more recent study is a multicenter one, performed on 349 PBC patients who were administered the dose of 3 mg/kg body weight daily (then adjusted to maintain serum levels above 75 ng/ml) and followed up for 6 years.73 All these studies reported a slight improvement on the biochemical expression of cholestasis but no effect on pruritus and on histology. The effect of cyclosporine on survival has been evaluated only in the multicenter study, and a significant delay of the progression of the disease could be observed only after adjusting for imbalance in prognostic variables.73 Moreover, the impact of cyclosporine on survival was also of limited extent. Side effects of cyclosporine, besides increase in serum creatinine levels, included hypertension, hirsutism, headaches, tremor, paraesthesias and abdominal discomfort and 5% of treated patients had to discontinue the drug. When considering the limited efficacy of this drug on survival, its side effects and its cost, it appears to be no indication for its clinical use in PBC.
A COVID-19 Risk Reduction Strategy for the Treatment of Acute Vogt-Koyanagi-Harada Disease Utilizing the Antiviral Potential of Cyclosporine
Published in Ocular Immunology and Inflammation, 2023
Makiko Nakayama, Annabelle A Okada, Isami Hayashi, Yoshimasa Ando, Takayo Watanabe, Hiroshi Keino
Table 1 summarizes the patient characteristics and treatment outcomes of all patients. The mean follow-up was 17.0 months (range 9–30 months). All patients received only one STTA administration bilaterally and were prescribed oral cyclosporine at an initial dose of 100 mg/day for patients 1 and 2 (body weight 55 kg), and 50 mg/day for patients 3 (body weight 45 kg) and 4 (body weight 45 kg). In patient 3, the cyclosporine dose was increased to 100 mg/day before successful cataract extraction in both eyes at 16 months, then tapered to 25 mg/day at 21 months (dose unchanged at the 30-month last follow-up). The cyclosporine was tapered to 50 mg/day at 14 months (last follow-up) in patient 2, and tapered to 50 mg/day at 6 months in patient 4 (dose unchanged at the 9-month last follow-up). The cyclosporine dose and duration details for patient 1 are in the Case Report. No recurrences of inflammation were observed, and there were no instances of re-thickening of the central choroidal thickness (measured at each clinic visit) observed over the follow-up duration. All patients continue a slow taper of cyclosporine without serious adverse effects. Mild renal dysfunction and mild anemia in the elderly patients are being managed with medical specialists, and were not judged to be a contraindication to continued cyclosporine therapy. None of the patients have developed late integumentary signs of VKH disease, and none have developed COVID-19 at last follow-up.
Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2023
Ariana Moreno, Yael Renert-Yuval, Emma Guttman-Yassky
Cyclosporine is a broad acting agent, which, among other immune effects, inhibits IL-2 and subsequently diminishes T-cell proliferation [142]. In adult AD, clinical improvement was associated with decreased Th2- (IL-13, CCL17) and Th17/Th22- (IL-22, S100As, elafin/PI3) related markers in AD lesions [146]. While many pediatric AD patients experience improvements in pruritis, sleep disturbances, proportion of skin affected, irritability, and TCS requirements by week 6 of treatment, the majority of patients relapse when the drug is stopped [147]. Primary concerns for long termlong-term use of cyclosporine therapy are drug toxicities, including nephrotoxicity, hyperkalemia, hypertrichosis, hypertriglyceridemia, parathesias and headaches [148]. A possible regimen to mitigate potential adverse events and cyclosporine toxicity was demonstrated by a 20-week study on adolescents (10–14 years old) with a history of severe refractory AD (mean SCORAD>40) controlled on continuous oral cyclosporine therapy. Switching from continuous to intermittent dosing (5 mg/kg on Saturdays and Sundays) was found to still be effective in controlling AD [149]. Another approach to minimize cyclosporine-related adverse events is a longer continuous course of low-dose cyclosporine which may be more beneficial in preventing disease relapse in children [138,148]. In sum, while cyclosporine has is effective for pediatric AD, severe potential adverse events are a major limitation of this treatment, especially when used long term, and relapse is frequent upon cessation of treatment.
Biologic therapy in relapsing polychondritis: navigating between options
Published in Expert Opinion on Biological Therapy, 2022
Roberto Padoan, Debora Campaniello, Luca Iorio, Andrea Doria, Franco Schiavon
Conventional immunosuppressive agents, such as cyclophosphamide, azathioprine, methotrexate, cyclosporine and mycophenolate, should be administered in refractory patients or when a GC-sparing effect is needed. Intravenous pulse cyclophosphamide treatment or oral formulation (1 to 2 mg/kg up to 150 mg/day) may be reserved for severe organ involvement or life-threatening manifestations, like severe laryngotracheal involvement, nodular or necrotizing scleritis, aortitis and aseptic meningitis. There are not specific guidelines about treatment’s duration, but when a stable remission is achieved, cyclophosphamide should be replaced with methotrexate, azathioprine or mycophenolate mofetil, to avoid long-term toxicity and carcinogenicity. Generally, we prescribe methotrexate as first-line DMARD, especially for auricular, nasal, tracheal and joint disease. Azathioprine and mycophenolate mofetil are used as second-line treatment, after methotrexate failure. Cyclosporine is an option when other immunosuppressive agents fail, but its use is limited by several side effects.