Safety Of Cyclosporine Research Articles

Patients with adult minimal change nephrotic syndrome treated with long-term cyclosporine did not experience a reduction in their eGFR

The long-term efficacy and safety of cyclosporine (CyA) in the treatment of adult minimal change nephrotic syndrome (MCNS) was examined. The medical record of 15 patients diagnosed with MCNS by renal biopsy and treated with CyA for at least 2 years were reviewed. The mean administration period of CyA was 78.3 months. The mean CyA dose for the induction period was 2.1 ± 0.9 mg/kg and 1.7 ± 1.0 mg/kg for the maintenance period. The mean dose of prednisolone used during the induction period was 20.3 mg and 2.7 mg during the maintenance. The frequency of MCNS relapse was decreased to 0.5 times/year in patients treated with CyA, compared to treatment without CyA (2.4 times/y). Two cases of mild liver damage and 3 cases of elevated blood pressure were observed during the administration of CyA. These adverse effects improved after reducing the CyA dose or treatment with an antihypertensive agent. A decrease in the estimated glomerular filtraion rate (eGFR) was not associated with long-term CyA use. At our institution, patients who were treated for MCNS with CyA for at least 2 years experienced no deterioration in renal function.

P452 Long-term efficacy and safety of cyclosporine as a rescue therapy in acute, steroid-refractory severe ulcerative colitis

Background: Although cyclosporine is an accepted and effective therapeutic choice in patients with severe ulcerative colitis (UC), long term colectomy rate varies between 60 88% among patients in whom cyclosporine initially induced remission. The aim of our study was to evaluate the long-term outcome and the optimal duration of cyclosporine therapy in patients with acute, severe UC. Methods: 73 (40 females, 33 males; mean age at the diagnosis 31.7 years, mean disease duration 13.4 years) of 183 patients hospitalized for severe exacerbation of UC between January 1998 and June 2009 revealed steroid-refractory after intravenous methylprednisolone therapy. They underwent intravenous cyclosporine treatment for 5 days following oral treatment in the case of a good initial response. Results: The mean follow up after the initiation of cyclosporine therapy was 4.2 years. The median duration of cyclosporine therapy was 9.6 months. Side effects developed in 37 patients. 20 patients underwent early colectomy. Cyclosporine therapy had to be discontinued due to intolerable or severe side effects in 22 patients. Cyclosporine failed and late colectomy was performed in 14 of the 53 responders during the longterm follow up. Duration of cyclosporine treatment was significantly longer in those who avoided colectomy (5.4 vs. 13.3 months, p = 0.009). The optimal cut-point of the duration of cyclosporine therapy to avoid colectomy was 4.5 months. No association was revealed between the duration of cyclosporine therapy and the development of side effects. Conclusions: Cyclosporine is effective in acute, severe UC. After a median follow up of more than 4 years, 53.4% of the patients remained colectomy free. The optimal time for cyclosporine treatment proved to be 4.5 months.

Effectiveness and safety of cyclosporin A therapy in steroid dependent nephrotic syndrome in childhood

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

Long-term Efficacy and Safety of Cyclosporine as a Rescue Therapy in Acute, Steroid-refractory Severe Ulcerative Colitis

Long-term Efficacy and Safety of Cyclosporine as a Rescue Therapy in Acute, Steroid-refractory Severe Ulcerative Colitis

Clinical Outcome Evaluation following Cyclosporine a Treatment in Moderate to Severe Psoriasis: A Retrospective Study

This retrospective study was conducted on 193 patients treated in three Italian Psoriasis Units with the aim of evaluating the evolution of psoriasis severity and the safety of cyclosporin A (Sandimmun Neoral) in moderate to severe psoriasis, at the regimens usually employed in common clinical practice. Cyclosporin A (CyA) was administered for a mean period of 14 months, the mean number of treatment courses was 1.6 (range 1-4), and the mean dosage ranged from 1.5 to 3.1 mg/kg/die. Ninety percent of patients obtained complete therapeutic success or clinical remission, defined as complete clearance of lesions or clearance of lesions with residual minor pigmentations respectively, when treated with CyA in monotherapy. The mean Psoriasis Area and Severity Index (PASI) decreased from 23.31 before CyA administration to 5.64 at the end of treatment. The clinicians judgement on CyA tolerability was good/very good in 90 percent of cases. Adverse events occurred in 36 percent of patients, with hypertension being the most commonly reported (17.6 percent). The results of this study indicate that in the common clinical practice CyA in moderate to severe psoriasis is usually employed at low doses, resulting both safe and effective.

Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice

We investigated the efficacy and safety of cyclosporine A (CsA; targeted serum trough level: 80-150 ng/ml) in a daily clinical practice for treating patients with systemic lupus erythematosus (SLE), who had been, or were expected to be, refractory to glucocorticoids (GCs) and other immunosuppressants. Fifty-nine patients with SLE receiving CsA were observed for at least 6 months (21.5 months on average). A significant reduction of proteinuria was noted 2 weeks after initiation of treatment in patients with nephritis, resulting in a clinical response in five of eight patients in the GC dose-up group and 11 of 18 patients in the stable GC dose group, respectively. Notably, the mean score for disease activity on the SLE Disease Activity Index decreased significantly from 8.6 +/- 5.3 to 4.4 +/- 2.5 after CsA treatment in patients in the stable GC dose group (n = 40). Moreover, the mean flare rate decreased by approximately 60% with CsA. Side effects of CsA appeared in 32.2% of patients and all of them subsided through dose reduction or discontinuation (n=8) of CsA. Consequently, the cumulative 2-year survival rate of CsA was 75%. The results suggest that CsA should be considered for patients with SLE refractory to GCs.

Safety of Cyclosporine in Warm Ischemia Transplanted Kidneys: A Selective Review

AbstractBACKGROUNDImmunosuppressive agents may have an impact on ischemia/reperfusion injury. Both renal warm ischemia (RWI) and cyclosporine may contribute to chronic allograft dysfunction and delayed graft function (DGF). Interaction between cyclosporine and RWI in generating renal injury is a controversial area.METHODSA search of the Medline database and OVID was done to identify articles related to the effects of cyclosporine on RWI.RESULTSBoth animal and human studies demonstrated detrimental effects of cyclosporine on injury and fibrosis in the kidney subjected to a period of RWI.CONCLUSIONSCyclosporine can sensitize the kidney to fibrosis induced by RWI. We recommend alternative approaches in immunosuppression including reduction in cyclosporine or cyclosporine‐free protocols when RWI is expected, as in non‐heart‐beating donors or in hemodynamically unstable donors.

P121 - The efficacy and safety of cyclosporine (CSA) and infliximab (IFX) in colitis ulcerosa (CU). Results in IBD-HOT follow-up study

P121 - The efficacy and safety of cyclosporine (CSA) and infliximab (IFX) in colitis ulcerosa (CU). Results in IBD-HOT follow-up study

Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie.

First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion. We conducted a controlled multicentre randomized open label trial to test the efficacy and safety of cyclosporin A (CSA) versus cyclophosphamide pulses (CPH) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease, focal segmental glomerulosclerosis or mesangial hypercellularity. Patients in the CSA group (n = 15) were initially treated with 150 mg/m(2) CSA orally to achieve trough levels of 120-180 ng/ml, while patients in the CPH group (n = 17) received CPH pulses (500 mg/m(2) per month intravenous). All patients were on alternate prednisone therapy. Patients with proteinuria >40 mg/m(2) per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses. At week 12, nine of the 15 (60%) CSA patients showed at least partial remission, evidences by a reduction of proteinuria <40 mg/h per m(2). In contrast, three of the 17 (17%) CPH patients responded (p < 0.05, intention-to-treat). Given these results, the study was stopped, in accordance with the protocol. After 24 weeks, complete remission was reached by two of the 15 (13%) CSA and one of the 17 (5%) CPH patients (p = n.s.). Partial remission was achieved by seven of the 15 (46%) CSA and two of the 15 (11%) CPH patients (p <0.05). Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study, most of them during the non-responder protocol. The number of adverse events was comparable between both groups. We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children.

Cyclosporine in chronic idiopathic urticaria with positive autologous serum skin test

This small study evaluates the effectiveness and safety of cyclosporine (CsA) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test (ASST), who fail to respond to conventional therapy, and requiring long-term oral steroid treatment. This small study evaluates the effectiveness and safety of cyclosporine (CsA) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test (ASST), who fail to respond to conventional therapy, and requiring long-term oral steroid treatment. Small open-label trials suggest that cyclosporine (CsA), used at a range of different daily dosages (<5 mg/kg) and duration, could be of therapeutic value in patients with chronic idiopathic urticaria (CIU) that is unresponsive to conventional therapy.1–4 Five adult patients (4 females and 1 male) in the age group of 20-50 years with mean age of 37.8 years with severe disease ranging from 6 weeks to 5 years (Table 1), unresponsive to antihistamines and showing a positive ASST, were advised to take 3 mg/kg per day of CsA for 12 weeks after taking consent for treatment, along with cetirizine (10 mg). Exclusion criteria included other concomitant forms of urticaria, any contraindications to cetirizine and CsA, and relevant systemic disorders. The clinical efficacy was measured with an activity score of wheal numbers and itch (Urticaria Activity Score, UAS). All patients were followed up to assess response to treatment. Table 1 Distribution of patients by sex and disease duration All patients were reviewed at 0,2,4,8 and 12 weeks with urticaria activity score. The UAS consists of the sum of the wheal number score and the itch severity score.5 The wheal numbers are graded from 0 to 3 as follows: 0 - less than 10 small wheals (diameter, 3 cm); 2 - greater than 50 small wheals or 10 to 50 large wheals; and 3 - almost the whole body is covered. The severity of itching is graded from 0 to 3 (0, none; 1, mild; 2, moderate; and 3, severe). Baseline investigations included urine examination, complete blood count, blood sugar, urea, creatinine and serum electrolytes. Repeat tests were done at 2, 4, 8 and 12 weeks. Blood pressure was monitored every two weeks. Average urticaria activity score was 5.4. Within two weeks of starting cyclosporine, the score came down to 1.6. The male patient discontinued cyclosporine due to high cost of therapy. Score came down to less than one in all four female patients who continued treatment. Side effects were few. In one patient, blood pressure went up 120/90 mm of Hg requiring amlodipine (2.5 mg) therapy. By the end of treatment, 3/4 (75%) patients were in full remission (score 0) and the remainder scored 1. This uncontrolled study has shown that low-dose CsA is effective in treating CIU patients, and can be given safely for 3 months. One study showed that prolonged treatment with CsA is beneficial for maintaining remission in severe cases of CU. It spares the need for corticosteroids and is accompanied with mild side effects.6 We could not perform ASST after stopping treatment, but one study from Italy has shown that ASST becomes negative in majority of patients with remission of symptoms.7 Methotrexate can be used in patients who cannot afford cyclosporine as reported by us.8

Safety of Cyclosporin A in HCV‐Infected Patients

Because of the relatively high prevalence of both hepatitis C virus (HCV) infection and autoimmune disorders (ADs), it is not rare to encounter in daily clinical practice patients with ADs also carrying HCV. Corticosteroids and/or immunosuppressant drugs are needed to treat ADs, but they place HCV-infected patients at risk of worsening the infection. So, rheumatologists have often refrained from using corticosteroids or immunosuppressants in AD when HCV-RNA is also present. Cyclosporin A (CsA) is an immunosuppressive agent used to treat a wide range of ADs, but there is a large evidences in the literature, both in vitro and in vivo, suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. Therefore, this evidence has opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases, including those with transplants. Recent reports, although limited in number, also suggest the safety of CsA in the treatment of patients with AD and concomitant HCV infection. In this review we also report our personal experience on the combination treatment with CsA and anti-TNF-alpha agents in rheumatoid arthritis.

Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis

The calcineurin inhibitors cyclosporine and tacrolimus are important treatments for patients with active rheumatoid arthritis, especially in cases of resistance or intolerance to methotrexate or other disease-modifying antirheumatic drugs. Here, we discuss the mechanism, efficacy and safety of cyclosporine and tacrolimus in the treatment of rheumatoid arthritis. Recent clinical trials of cyclosporine have shown the advantages of its combination with methotrexate, glucocorticoids and leflunomide in the treatment of active rheumatoid arthritis. In Japan, tacrolimus monotherapy was found to be quite effective and combination therapy with methotrexate had positive results in an American study. The inhibitory effects of both drugs not only on T lymphocytes, but also on human osteoclast formation, have been demonstrated in basic studies. Cyclosporine and tacrolimus are clinically available disease-modifying antirheumatic drugs. Numerous clinical studies have shown the usefulness of these calcineurin inhibitors in monotherapy and also when combined with methotrexate. Although these drugs have similar effects, there are some differences in adverse reactions.

Cyclosporin in the treatment of patients with atopic eczema – a systematic review and meta‐analysis

To systematically assess the effectiveness of systemic cyclosporin in patients with severe atopic eczema. Systematic review and meta-analysis of controlled and uncontrolled trials. Electronic (MEDLINE, Cochrane databases) and hand search of published work. Independent standardized assessment of eligibility and data abstraction by two reviewers. For the qualitative review data on study design, study population, methodology, results, tolerability and methodological quality was independently extracted by two reviewers. Qualitatively homogeneous studies were pooled using a random-effects model. The mean relative change in objective disease severity was chosen as the main outcome measure for the quantitative analysis. Publication bias was explored by regressing treatment effect on sample size. Sensitivity analysis included meta-regression of study-specific covariates (inclusion of children, study type, concomitant topical therapy, study quality). Fifteen studies including 602 patients met the eligibility criteria. In all studies analysed, cyclosporin consistently decreased the severity of atopic eczema. Twelve studies appeared homogeneous enough to be pooled. After 2 weeks of treatment we found a dose-related response with a pooled mean decrease in disease severity of 22% (95%-CI 8-36%) under low-dose cyclosporin ( 3 mg/kg) and 40% (95%-CI 29-51%) at dosages >or=4 mg/kg. After 6-8 weeks the relative effectiveness was 55% (95%-CI 48-62%). Due to evidence of publication bias the quantitative results need to be interpreted with caution. Effectiveness of cyclosporin is similar in adults and children, but tolerability might be better in children. As data to adequately evaluate the long-term effectiveness and safety of cyclosporin in patients with atopic eczema are unavailable, long-term registries are encouraged.

Clinical evaluation of efficacy and safety of cyclosporine (Imusporin) in renal transplant patients with stable graft function maintained on neoral or bioral

Objective:Previous pharmacokinetic studies have demonstrated bioequivalence of Imusporin (microemulsion preparation of cyclosporine, Cipla) to the innovator product Neoral (Novartis, Switzerland). This study was done to evaluate the clinical efficacy and safety of Imusporin in patients who have already undergone renal transplant and have stable graft function maintained on cyclosporine preparation other than Imusporin.Materials and Methods:Twenty-two renal allograft recipients (mean age of 31.77 years, range 18-53 years), with stable graft function, previously on Neoral or Bioral were switched over to Imusporin after recording their relevant baseline clinical and biochemical parameters. These were repeated on 1, 4, 7, 15, 30 and 90 days after the start of therapy. Change in dosage required to maintain C2 levels at each visit were analyzed by paired sample t-test. Safety of the drug was assessed by the type and severity of adverse events developed during the therapy. Cost analysis was done assuming an average maintenance immunosuppression dose of 150 mg/day of cyclosporine.Results:Twenty-one patients completed the study. One patient was lost to follow-up. Mean C2 value before switchover was 894 ± 208 ng/ml, which was not significantly different from the mean values of C2 after switchover therapy (P>0.30). Change in dosage required to maintain C2 levels was not significantly different from the baseline dose of 2.34 mg/ kg body weight (P>0.1). No patient developed graft rejection after switchover therapy at a median follow-up of 16 months (14-18 months). Mean baseline SCr was similar to SCr at day 90 (1.38 vs. 1.37 mg/dl, P=0.930). No severe adverse events were reported. Mild side-effects included headache (4), somnolence (2), dry mouth (5) and generalized fatigue (6). Use of Imusporin (Cipla, India) results in an annual savings of Rs. 19892 over Neoral (Novartis, Switzerland) and Rs. 2263 over Bioral (Panacea Biotech, India).Conclusions:Imusporin is clinically as safe and efficacious as other cyclosporine preparations available while significantly reducing the cost of treatment.

Efficacy and Safety of Cyclosporine in the Treatment of IBD in Children: Retrospective Analysis

Efficacy and Safety of Cyclosporine in the Treatment of IBD in Children: Retrospective Analysis

TGF-β1 mRNA upregulation influences chronic renal allograft dysfunction

Acute rejection (AR) is a dominant risk factor for developing chronic allograft nephropathy (CAN) after kidney transplantation. CAN is characterized by progressive interstitial fibrosis. It has been associated with increased transforming growth factor (TGF)-beta1 expression, however, kinetic studies are absent. We investigated whether intragraft TGF-beta1 expression in various causes of early graft dysfunction may influence late renal allograft dysfunction. A total of 174 human renal biopsies were quantified for TGF-beta1 mRNA expression using real-time reverse transcriptase-polymerase chain reaction. Expression levels were correlated with the Banff histopathological grades, TGF-beta1 immunohistology, and clinical follow-up. TGF-beta1 was most markedly upregulated in AR, CAN, and acute tubular necrosis - delayed graft function compared to non-rejecting controls (P < 0.001). TGF-beta1 expression was heightened in borderline changes (P < 0.01), recurrence of glomerulonephritis, and cyclosporine toxicity (P < 0.05). There was no correlation between intragraft TGF-beta1 expression during AR and short-term outcome of a rejection episode. TGF-beta1 gene overexpression during CAN has been shown to be associated with the increased risk for renal allograft dysfunction 18 months after biopsy (odds ratios 9.9 vs 3.2, respectively). Intragraft TGF-beta1 mRNA expression is significantly upregulated in both AR and CAN. Thus, our results support the hypothesis that TGF-beta1 might play a key role in chronic allograft dysfunction.

Long-Term Trends in Allograft Survival

Kidney transplantation has changed dramatically over the past decade. Many advances have occurred that result in shorter hospital stays, decreased acute rejection, less infectious morbidity, and improved long-term allograft survival. Many factors are responsible for the improvement in kidney transplantation, and these factors are discussed in this review. These successes have led to a paradox in the care of the kidney-transplant recipient, however. As the short-term complications are prevented or successfully managed, more patients will develop chronic problems with the function of the allograft.

Intraocular implantation of cyclosporine A drug delivery system in the treatment of experimental uveitis

To investigate the effects and safety of cyclosporine A drug delivery system (CsA DDS) implanted into vitreous cavity on the treatment of experimental rabbit uveitis. A model of uveitis was established in 30 New Zealand white rabbits (30 eyes). The rabbits were randomized into control group (group A, 6 eyes), intravitreal non-medicated DDS group (group B, 6 eyes), oral CsA group (group C, 6 eyes) and intravitreal CsA DDS group (group D, 12 eyes). The inflammatory parameters such as floating cells, flaring and exudation in anterior chamber were graded. The cells infiltration and degree of opacity in vitreous were scored as well. The electroretinography and histopathological examination in eye, liver and kidney were recorded. In addition, CsA level in vitreous cavity was measured by HPLC in another 13 New Zealand white rabbits that received intravitreal implantation of CsA DDS. Uveitis was successfully induced in the 30 eyes. The inflammation in groups A, B and C was more severe than group D. There was no significant difference between groups D and A or B (P < 0.05). The electroretinography showed more significant b-wave depression in groups A and B than group D (P < 0.05). A large amount of inflammatory cells infiltration and marked tissue disorganization were found at ciliary body and retina in groups A and B. The mean drug level in vitreous cavity ws (491.0 +/- 481.6) ng/ml at 4 weeks, (575.2 +/-0373.2) ng/ml at 8 weeks and (301.5 +/- 128.5) ng/ml at 12 weeks. No toxicity could be detected in histological examination by light microscopy. Sustained therapeutic drug level could be achieved by implanting CsA DDS into vitreous cavity. It may effectively reduce the ocular inflammation in the rabbit model of uveitis.

Clinical trial evaluating the efficacy and safety of cyclosporine in dogs with atopic dermatitis

To determine efficacy and safety of cyclosporine in the treatment of atopic dermatitis among dogs in North America. Randomized controlled (phase 1) and open-label (phase 2) trials. 268 dogs with atopic dermatitis. In phase 1, dogs were randomly assigned to be treated with cyclosporine (5 mg/kg [2.3 mg/Ib], PO, q 24 h) or a placebo. In phase 2, all dogs were treated with cyclosporine for 16 weeks. Frequency of cyclosporine administration was decreased if dogs improved clinically. At the end of phase 1, canine atopic dermatitis extent and severity index (CADESI) scores for dogs treated with cyclosporine were significantly lower than scores for control dogs. Percentage of dogs with severe pruritus decreased from 67% to 16% for the cyclosporine group but from 66% to only 61% for the control group. During phase 2, cyclosporine dosage was decreased to every-other-day administration in 39% of the dogs after 4 weeks. After 12 weeks, 22% of the dogs were treated twice weekly and 36% were treated every other day. After 16 weeks, CADESI score had decreased > 50% in 68% of the dogs and 47% of dogs had no or mild pruritus. The most frequent adverse reactions were gastrointestinal tract signs. Results suggest that cyclosporine is efficacious for the treatment of atopic dermatitis in dogs and that frequency of cyclosporine administration can be reduced following an initial induction period. The drug was well tolerated.

Safety of cyclosporine in patients with psoriasis

Safety of cyclosporine in patients with psoriasis