Safety Of Cyclosporine Research Articles

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908–8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Comparison of tacrolimus vs. cyclosporine in pediatric hematopoietic stem cell transplantation for thalassemia.

Graft-versus-host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. Despite the GvHD prophylaxis, grade II-IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI-related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno-occlusive disease, CMV reactivation, PRES, or graft rejection. Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.

Long‐term results and persistence of topical cyclosporine a 0.1% treatment in patients with dry eye disease in a tertiary eye centre

Aims/Purpose: This study aims to assess clinical effectiveness, outcome and safety of long‐term topical Cyclosporine A 0.1% Cationic Emulsion (CsA 0.1% CE; Ikervis®) treatment in patients with dry eye disease.Methods: Retrospective chart review of 55 patients (110 eyes) with dry eye disease and severe keratitis treated with Ikervis® since 2016 for at least 12 months without interruption was performed. Study outcomes were median change from baseline in corneal fluorescein staining (CFS, Oxford Grade Scale) score, clinical outcome, treatment discontinuation reason, ocular symptom severity and adverse events (AEs) during long follow‐up.Results: The mean age of patients was 65.96 ± 1.9 years, 81.8% women and 18.2% men. The mean follow‐up was 33.8 ± 19.1 (12–80) months. 43.6% eyes had grade III of CFS at baseline and 4.5% had grade I of CFS at the last follow up. The median CFS score reduced from 2 (1–3) at baseline to 0 (0–1) at the last follow up and this reduction was statistically significant (p < 0.001) from the fourth week. Clinical outcome was defined as active/worsening in 1.8%, stabilization in 14.5%, improvement in 69.1% and resolution in 14.5% of the cases. 65.5% of the patients have continued the treatment without interruption during the whole follow‐up, the treatment discontinuation in 35.5% of the cases were due to improvement (14.5%), AEs (5.5%), patient decision (5.5%), treatment failure (3.6%), other reason (5.5%). Ocular symptom severity was significantly reduced from baseline during the follow up (p < 0.001). In 27.3% cases treatment‐related AEs were reported, most of them (64.7%) were mild.Conclusions: This study shows a long‐term clinical effectiveness and persistence of the topical CsA 0.1% CE treatment in patients with dry eye disease. The significantly reduction of the dry eye symptoms severity from the fourth week of the initiated Ikervis® treatment sustains for a long follow up, and thus definitely improves the quality of life of patients.Reference1. Geerling G, Hamada S, Trocmé S, Ræder S, Chen X, Fassari C, Lanzl I; PERSPECTIVE study group. Real‐World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment. Ophthalmol Ther 2022; 11(3): 1101–1117. doi: 10.1007/s40123‐022‐00487‐x.

Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis.

Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy. We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC. Monocentric, prospective study. We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy. Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated. Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies. Not applicable.

The efficacy and safety of cyclosporine in children with systemic lupus erythematosus: A protocol for systematic review and meta-analysis.

Childhood-onset systemic lupus erythematosus (SLE) is a rare but severe multisystem autoimmune/inflammatory disease with marked heterogeneity between patients, causing anything from mild to life-threatening disease. We performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of cyclosporine in childhood-onset SLE. This systematic review has been registered in PROSPERO (CRD42022377450), which will be conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Only randomized controlled trials will be included.We searched the following databases including PubMed, EMBASE, the Cochrane Library, SinoMed, CNKI, VIP, Wanfang Data and International Clinical Trials Register Search Portal, and Clinical Trials.gov. Two researchers will use the Cochrane systematic evaluation tool to assess the risk of bias independently. Data synthesis will be performed using RevMan V.5.4. This study will comprehensively summarize the high-quality trials to determine the efficacy and safety of cyclosporine in the treatment of childhood-onset SLE. This study may be beneficial to health policymakers, clinicians, and patients with regard to the use of cyclosporine in childhood-onset SLE.

Cyclosporine A Delivery Platform for Veterinary Ophthalmology-A New Concept for Advanced Ophthalmology.

Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as a medication for a wide spectrum of diseases in humans such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis. Furthermore, the CsA is used to treat keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis and equine recurrent uveitis in animals. The selective activity of Cyclosporine A (CsA) was demonstrated to be an immunomodulation characteristic of T-lymphocyte proliferation and inhibits cytokine gene expression. Moreover, the lipophilic characteristics with poor bioavailability and low solubility in water, besides the side effects, force the need to develop new formulations and devices that will provide adequate penetration into the anterior and posterior segments of the eye. This review aims to summarize the effectiveness and safety of cyclosporine A delivery platforms in veterinary ophthalmology.

The efficacy and safety of cyclosporine A plus androgen versus androgen alone for adult patients with non-severe aplastic anemia in China: a meta-analysis of randomized controlled trials

ABSTRACT Background Whether combined CsA with androgen therapy was superior to androgen therapy alone in NSAA remains controversial. This study aimed to assess the efficacy and safety of combined therapy versus androgen therapy for NSAA patients using a meta-analytic approach. Methods An electronic database of PubMed, EmBase, Cochrane library, CNKI, VIP, and Wanfang was systematically searched for randomized controlled trials (RCTs) from their inception to February 2020. The primary endpoint was effective rate, while the secondary endpoints included white blood cell (WBC), hemoglobin, platelet, and potential adverse events. The pooled results from included trials were calculated with the random-effects model. Results Forty-three RCTs recruited 2610 NSAA patients for the final quantitative meta-analysis. We noted that combined therapy was associated with an increased incidence of effective rate than androgen therapy alone (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.29–1.41; P < 0.001). Moreover, patients treated with combined therapy were associated with higher WBC (weighted mean difference [WMD]: 1.22; 95%CI: 0.94–1.49; P < 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86–17.01; P < 0.001), and platelet (WMD: 8.65; 95%CI: 7.05–10.24; P < 0.001). Finally, the pooled incidence of hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage were 0.35 (95%CI: 0.22–0.48), 0.24 (95%CI: 0.15–0.32), 0.22 (95%CI: 0.10–0.35), 0.19 (95%CI: 0.14–0.25), and 0.06 (95%CI: 0.01–0.11), respectively. Conclusions This study found that combined CsA with androgen therapy was superior to androgen therapy alone for Chinese patients with NSAA, and the most common adverse of combined therapy included hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage.

Effectiveness and Safety of Cyclosporine A in Childhood Nephrotic Syndrome.

Effectiveness and Safety of Cyclosporine A in Childhood Nephrotic Syndrome.

Real-World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment.

IntroductionThe PERSPECTIVE study evaluated, in routine clinical practice, the effectiveness, tolerability and safety of cyclosporine A (CsA) 0.1% cationic emulsion (CE) in controlling severe keratitis in adults with dry eye who remained insufficiently controlled despite artificial tear (AT) use.MethodsA prospective, multicenter, observational study was conducted at 44 ophthalmology clinics across Finland, Germany, Norway, Sweden and the UK. Adults treated with ATs for severe keratitis and dry eye received CsA 0.1% CE therapy (1 drop in both eyes at bedtime) and were followed up at weeks 4, 12 and 24 and at month 12. Primary endpoint was mean [standard deviation (SD)] change from baseline in corneal fluorescein staining (CFS; Oxford Grade Scale) at month 12 following CsA 0.1% CE initiation. Secondary endpoints examined ocular sign and symptom severity and adverse events (AEs).ResultsThe full analysis set included 472 adults (75.9% female). Mean (SD) age was 61.9 (15.41) years. Mean (SD) CFS score was significantly reduced from baseline [2.56 (1.10)] at month 12 [1.10 (SD 1.13); P < 0.0001]. CFS score reductions were statistically significant from week 4, with further incremental decreases reported at study visits through month 12 (P < 0.0001). Severity of eyelid and conjunctival erythema was significantly reduced from baseline at week 4 and maintained through month 12 (P < 0.001). Tear film breakup time increased significantly from baseline at all study visits through month 12 (P < 0.001). Ocular symptom severity was significantly reduced from baseline at all study visits through month 12 (P < 0.001). Overall, 101 treatment-related AEs were reported. Most were mild/moderate (83.6%) and resolved by month 12 (73.3%).ConclusionsIn routine clinical practice, CsA 0.1% CE provided statistically significant reductions in dry eye signs and symptoms. Improvements were seen at week 4 and maintained over 12 months. Treatment tolerability was good and consistent with previous CsA 0.1% CE clinical studies.Trial registrationEU PAS register number: EUPAS 22376.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00487-x.

Efficacy and safety of cyclosporine A treatment in autoimmune cytopenias: the experience of two Italian reference centers.

Background:Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) show good responses to frontline steroids. About two-third of cases relapse and require second-line treatment, including rituximab, mainly effective in AIHA, and thrombopoietin-receptor agonists (TPO-RAs) in ITP, while the use of splenectomy progressively decreased due to concerns for infectious/thrombotic complications. For those failing second line, immunosuppressants may be considered.Objectives:The aim of this study was to evaluate the efficacy of cyclosporine treatment in patients with ITP and AIHA.Design:In this retrospective study, we evaluated the efficacy and safety of cyclosporine A (CyA) in ITP (N = 29) and AIHA (N = 10) patients followed at two reference centers in Milan, Italy.Methods:Responses were classified as partial [Hb > 10 or at least 2 g/dl increase from baseline, platelets (PLT) > 30 × 109/l with at least doubling from baseline] and complete (Hb > 12 g/dl or PLT > 100 × 109/l) and evaluated at 3, 6, and 12 months. Treatment emergent adverse events were also registered.Results:The median time from diagnosis to CyA was 35 months (3–293), and patients had required a median of 4 (1–8) previous therapy lines. Median duration of CyA was 28 (2–140) months and responses were achieved in 86% of ITP and 50% of AIHA subjects. Responders could reduce or discontinue concomitant treatment and resolved PLT fluctuations on TPO-RA. CyA was generally well tolerated, and only two serious infectious complications in elderly patients on concomitant steroids suggesting caution in this patient population.Conclusion:CyA may be advisable in ITP, which is not well controlled under TPO-RA, and in AIHA failing rituximab, particularly if ineligible in clinical trial.

The effectiveness of cyclosporine A for patients with steroid-resistant nephrotic syndrome: A protocol for systematic review and meta-analysis.

Background:The purpose of this study is to determine the efficacy and safety of Cyclosporine A (CsA) for patients with steroid-resistant nephrotic syndrome (SRNS).Methods:This study will be designed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies are identified through systematic searches in November 2021 with no restrictions on date and time, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The risk of bias of included studies is estimated by taking into consideration the characteristics including random sequence generation, allocation concealment, blinding of patients, blinding of outcome assessment, completeness of outcome data, selective reporting, and other bias by Cochrane Collaboration's tool. Data synthesis and analyses are performed using Stata version 10.0 software.Results:The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.Conclusion:CsA may be an effective and safe therapy for SRNS. However, additional randomized controlled studies are needed to thoroughly assess the role of CsA in the treatment of SRNS.Open Science Framework registration number:10.17605/OSF.IO/P6YB9

Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all P>0.05).After 6 months of treatment,CsA+rhEPO group had higher overall response(OR)rate(55.6% vs. 31.3%;χ 2=4.456,P=0.040)and partial response(PR)rate(53.3% vs. 25.0%;χ2=6.181,P=0.019)than CsA group,and the complete response(CR)rate showed no statistical difference between the two groups(2.2% vs. 6.3%;χ2=0.810,P=0.567).The CR,PR,and OR rates showed no statistical difference between the two groups after 3 and 12 months of treatment and at the end of follow-up(all P>0.05).Similarly,the hemoglobin level at the sixth month of treatment with CsA+rhEPO was higher than that with CsA alone [(102.6±24.0)g/L vs.(90.3±29.1)g/L;t=2.017,P=0.047].However,it showed no significant difference between the two groups at other time points(all P>0.05).The side effects,including an increase in serum creatinine,slight increase in bilirubin,increase in aminotransferase,mild to moderate gingival hyperplasia,gastrointestinal reaction,and muscular fibrillation,had no significant differences between the two groups(all P>0.05),except that 11.1%(5/45)patients in the CsA+rhEPO group reported soreness at the injection site.The two groups showed similar rates of clonal revolution during the follow-up period and no death.No clinical factor was found for prediction of the efficacy of CsA+rhEPO. Conclusion CsA+rhEPO has higher OR rate and hemoglobin level than CsA alone at the sixth month of treatment,and it has similar side effects compared with CsA alone.

P-81 ALTERNATIVE THERAPIES FOR DIFFICULT-TO-TREAT AUTOIMMUNE HEPATITIS: AN EXPERIENCE OF THREE BRAZILIAN REFERRAL CENTERS

15% of patients with autoimmune hepatitis (AIH) are refractory to usual treatment. The management of these cases is still challeging. To evaluate the efficacy and safety of cyclosporine (CYA), mycophenolate (MMF) and tacrolimus (FK). This is a retrospective study with alternative therapies (AT) for non-response or intolerance to azathioprine (AZA) and prednisone (PD). Biochemical remission (BR) was defined as the normalization of AST and ALT; and histological remission (HR) as periportal activity 0/1 or histological activity index <4 after at least 18 months of BR. Liver enzymes before and after AT were compared by Wilcoxon Test and categorical variables by Chi-square test; p value ≤0.05 was significant. 60 patients (88.3% female, 86.7% type 1 AIH). At diagnosis 56.7% had cirrhosis, 15% ascites. AZA+PD was the initial regimen in 75%. The median time AT onset was 2.23 yr. AT was introduced due to absence of BR (26.7%), absence of BR + adverse effects (AE) of AZA (11.7%), of AZA/PD (50%), BR without HR (6.7%) and liver dysfunction (3.3%). The main AE were from AZA: hepatotoxicity (10), gastrointestinal intolerance (10) and cytopenias (8). At AT onset, 65% were using AZA+PD. AT were MMF+PD (36.7%) and CYA+AZA±PD (30%). After 6 and 12m of AT there was significant drop in AST/ALT/ γGT. BR and HR were achieved in 53.3% and 8.3% respectively. In those with BR, HR occurred in 15.6%. Cirrhosis at diagnosis resulted in lower BR. AD was used for a median of 2.7 yr; 28% had AE (gingival hyperlasia, infection and diarrhea). AT were withdrawn in 33.3%: non-response (5), liver dysfunction (4), AE (4), HR (3), infections (2), pregnancy (1) and loss of follow-up (1). Five patients transplanted and 1 died. Although BR was acceptable in difficult-to-treat AIH, HR was low and AT was withdrawn due to non-response in 8% and liver dysfunction in 6.6%. AT were well tolerated, with few AE. Prospective studies with a larger sample size are still needed.

Successful treatment of corticosteroid-dependent drug reaction with eosinophilia and systemic symptoms with cyclosporine

BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is an intractable drug hypersensitivity disease with high mortality. The current standard treatment requires high-dose and long-term systemic corticosteroids, which may lead to adverse effects and intolerability of patients. ObjectiveTo evaluate the efficacy and safety of cyclosporine in patients with corticosteroid-dependent DRESS or intolerance to systemic corticosteroids. MethodsA retrospective review of 8 patients with corticosteroid-dependent DRESS who were treated with cyclosporine as an alternative treatment owing to suboptimal response to regular doses of systemic corticosteroids for at least 3 weeks, flare-ups when tapering corticosteroids, or experiencing intolerable adverse effects of corticosteroids. ResultsIn all 8 patients (4 women and 4 men; age range, 15-75 years), either intractable skin eruptions, persistent eosinophilia, or elevated liver function was noted after at least 3 weeks of treatment with systemic corticosteroids. The patients had marked cutaneous improvement and normalization of liver function and eosinophil count after adding cyclosporine, and the systemic corticosteroid treatment was smoothly tapered down. The mean dosage of cyclosporine was 1.68 ± 0.73 mg/kg/d, and the mean duration of cyclosporine treatment was 76.13 ± 35.64 days. Their serum eosinophil counts, serum alanine aminotransferase levels, and serum thymus and activation-regulated chemokine levels were all elevated at baseline and then significantly decreased during the recovery stage after cyclosporine therapy (P < .05). No adverse events were reported after adding cyclosporine. ConclusionCyclosporine is an effective and safe therapeutic alternative as a steroid-sparing agent for corticosteroid-dependent DRESS. Further prospective randomized controlled studies are required to confirm these preliminary results.

Isolated carotid webs – An uncommon cause of recurrent strokes

Severe cutaneous adverse drug reactions (sCADR) comprise the life-threatening Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Aim: The aim of this study was to assess the efficacy and safety of cyclosporine in treating sCADR. Materials and Methods: A retrospective study was done from data collected over a three year period at the department of dermato-venereo-leprology at a tertiary care centre in South India. Out of thirty-four in-patients with adverse drug reactions (ADRs), twenty who fulfilled the inclusion criteria (one DRESS, ten SJS and nine TEN patients) were taken for the study. Fixed drug eruption and TEN with multiorgan failure were excluded. Methodology: Patients were evaluated, screened for multiorgan involvement, offending drug/drugs were withheld, routine investigations done and the severity assessed based on SCORTEN. Treatment was initiated with injection dexamethasone 1mg/kg/day and supportives. In those with unsatisfactory response in three days, if not contra-indicated, oral cyclosporine was added at a dose of 100mg bid for 2 weeks, tapered by 50mg/week and stopped once the lesions healed. Efficacy of cyclosporine was assessed using the average number of stabilization days, the rate of cutaneous re-epithelialization and the duration of hospitalization. Results: For SJS, the mean duration of stabilization was 2 days, re-epithelialization 7.9 days and hospital-stay 18.1 days. For TEN, the mean duration of stabilization was 3.9 days, re-epithelialization 12.8 days and hospital-stay 29.2 days. Conclusion: With the use of cyclosporine, patients stabilized early, re-epithelialization occurred early; concomitant use with steroids helped in early tapering of steroid dose. Recovery time and duration of hospital stay were shortened. Cyclosporine was well tolerated, no significant toxicity was noted; there was no mortality. Keywords: Cyclosporine, Severe cutaneous adverse dru

Efficacy and safety of cyclosporine A in the treatment of idiopathic membranous nephropathy in an Asian population.

IntroductionThe efficacy of cyclosporine A (CsA) in the treatment of idiopathic membranous nephropathy (IMN) is unclear. This meta-analysis was conducted to assess the efficacy and the safety of CsA in the treatment of IMN in Asians.MethodsWe searched the Pubmed, China Biomedical Database, CNKI, Wanfang Data, VIP, and EMBASE (November 30, 2018) systematically to identify the appropriate randomized controlled trials (RCTs) reporting the efficacy and the safety of CsA and glucocorticoid (GC) treatment vs other immunosuppressants and GC on patients with IMN in Asian populations.ResultsThe CsA treated group entered complete remission (CR) faster (3 months) than a cyclophosphamide (CTX) group. While the CsA group lower inefficacy rates and higher total remission (TR, CR, or partial remission) than the CTX group in the total treatment (3 months, 6 months, and 12 months), it had a higher relapse rate. As for the CsA group vs the tacrolimus (TAC) group, the TAC had a significant effect in increasing the CR and the TR, with decreased no remission. With the therapeutic regimens of CsA+GC vs CTX+GC, the CsA exhibited better efficacy in lowering the proteinuria levels only at 12 months, not at 3 months or 6 months. Severe events like leucopenia, hemorrhagic cystitis, and alopecia were observed in the CTX group. Gingival hyperplasia, hirsutism, and elevated blood pressure were reported only in the CsA group. Gastrointestinal syndrome, liver function lesion, happened more frequently in the CTX group, and elevated uric acid was more common in the CsA group.ConclusionsIn brief, the CsA has better efficacy than the CTX group in the Asian population, with mild adverse effects but higher relapse rates in short-term treatment.

Efficacy and Safety of Cyclosporine in Children with Steroid-Dependent Nephrotic Syndrome

Efficacy and Safety of Cyclosporine in Children with Steroid-Dependent Nephrotic Syndrome

CNS Delivery and Anti-Inflammatory Effects of Intranasally Administered Cyclosporine-A in Cationic Nanoformulations.

The main objective of this study was to develop and evaluate the CNS delivery efficiency, distribution, therapeutic efficacy, and safety of cyclosporine A (CSA) using a cationic oil-in-water nanoemulsion system upon intranasal administration. An omega-3 fatty acid-rich, flaxseed oil-based nanoemulsion was used for intranasal delivery to the brain, and further magnetic resonance imaging (MRI) was used to evaluate and confirm the transport of the positively charged CSA nanoemulsion (CSA-NE) in CNS. Furthermore, the anti-inflammatory potential of CSA peptide was evaluated using the lipopolysaccharide (LPS) model of neuroinflammation in rats. CSA-NE showed a good safety profile when tested in vitro in RPMI 2650 cells. Upon intranasal administration in rats, the nanoemulsion delivery system showed higher uptake in major regions of the brain based on changes in MRI T1 (longitudinal relaxation time) values. Additionally, CSA nanoemulsion showed improved therapeutic efficacy by inhibiting proinflammatory cytokines in the LPS-stimulated rat model of neuroinflammation compared with solution formulation. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects in rats. Based on these results, intranasal delivery of CSA and other "neuroprotective peptides" may provide a clinically translatable strategy for treating neurologic diseases.

Infliximab versus cyclosporine for severe ulcerative colitis refractory to steroids: A protocol for systematic review and meta-analysis.

Background:Infliximab and cyclosporine are two main therapies in treating acute severe ulcerative colitis (ASUC), our objective is to assess the effectiveness and safety of cyclosporine (CSA) versus infliximab (IFX) as rescue agents in patients with steroid-refractory ulcerative colitis (UC).Methods:We will search three databases from inception to May 2018, and 19 studies are identified that infliximab and cyclosporine as a treatment in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months, 12 months, 36 months, adverse drug reactions and mortality in those who received rescue therapy.Results:This update review will provide a high quality synthesis of current evidence of two treatment for steroid-refractory ulcerative colitis. The definition of severe colitis is according to Truelove and Witts’ criteria.Conclusions:In the treatment of steroid-resistant ulcerative colitis with infliximab and cyclosporine, there is no difference between the two treatments on short-term and long-term results.

Mycophenolate mofetil versus cyclosporine A in children with primary refractory nephrotic syndrome

Objective: To compare the efficacy and safety of mycophenolate mofetil versus cyclosporine A in treating children with primary refractory nephrotic syndrome. Methods: Conducted a prospective randomized controlled clinical trial in 62 pediatric patients (including 44 boys and 18 girls), age ranged from 2.1 to 17.0 years; 32 cases presented with frequently relapsing nephrotic syndrome (FRNS) and 30 cases presented with steroid-resistant nephrotic syndrome (SRNS), who were admitted to department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from October 2013 to October 2015. The patients received either mycophenolate mofetil (20-30)mg/(kg·d) or cyclosporine A (3-5)mg/(kg·d) randomly, on the basis of prednisone treatment. Follow-up interview was conducted regularly for at least one year. Efficacy rate, relapse rate, time required for induction of remission, relapse-free period and prednisone dosage were compared between the two groups. Results: (1) Renal histologic examination, which was available for 17 patients, revealed minimal change disease in 8 patients, mesangial proliferative glomerulonephritis (MsPGN) in five, membranous nephropathy in two, and focal segmental glomerulosclerosis (FSGS) in two. (2) Comparison of mycophenolate mofetil versus cyclosporine A in children with FRNS: There were 14 patients with FRNS in mycophenolate mofetil group and 18 patients with FRNS in cyclosporine A group respectively. The relapse rate (episodes/year) in cyclosporine A group was lower than that of mycophenolate mofetil group (1.0 (0.0, 1.0) vs. 1.0 (1.0, 3.0), Z=-2.405, P=0.016). The relapse-free period (months) in cyclosporine A group was longer than that of mycophenolate mofetil group (10.0 (5.7, 12.1) vs. 5.0 (1.0, 11.0), Z=-1.984, P=0.047). No significant difference in dosage of prednisone was found between cyclosporine A and mycophenolate mofetil groups when followed up for 1 year. (3) Comparison of mycophenolate mofetil versus cyclosporine A in children with SRNS: The efficacy rate was 6/14 in mycophenolate mofetil group and 13/16 in cyclosporine A group. The complete remission rate was 4/14 in mycophenolate mofetil group and 12/16 in cyclosporine A group (P<0.05). The time (months) required for induction of remission in cyclosporine A group was significantly shorter than that of mycophenolate mofetil group (1.0 (1.0, 2.0) vs. 3.0 (2.5, 4.0), Z=-2.529, P=0.011). No significant differences were found between the two groups with respect to relapse-free period and relapse rate. (4) Except that one patient developed hypertensive encephalopathy in cyclosporine A group, no other serious adverse events were recorded. There were no significant differences between two groups with respect to adverse events. Conclusion: Our results indicated that both mycophenolate mofetil and cyclosporine A were effective in the treatment of children with refractory nephrotic syndrome. Cyclosporine A was superior to mycophenolate mofetil in preventing relapses in patients with FRNS and inducing complete remission in patients with SRNS. Although most patients were able to tolerate mycophenolate mofetil and cyclosporine A, but the toxicity and safety of cyclosporine A should be monitored closely.