Safety Of Cyclosporine Research Articles

Efficacy and Safety of Cyclosporine in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI −0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.

Ciclosporina no Tratamento da Urticária Crónica Espontânea na Era do Omalizumab

Introdução: Na urticária crónica espontânea (UCE) refratária a anti-histamínicos, as recomendações nacionais propõem utilizar o omalizumab mas este nem sempre está prontamente disponível, justificando-se discutir o valor de outros fármacos. Neste contexto, analisámos a eficácia e a segurança da ciclosporina e explorámos a relação entre características da urticária e a resposta terapêutica.Material e Métodos: Estudo retrospetivo num serviço de dermatologia (2010-2016). Foram reunidos dados demográficos, clínico-evolutivos e laboratoriais da UCE moderada a grave tratada com ciclosporina, dose, duração do tratamento, período de follow-up e reações adversas. A eficácia foi avaliada pela escala de atividade da urticária durante 7 dias (UAS7). A significância estatística foi definida para 0,05.Resultados: Foram estudados 23 doentes (19 feminino/4 masculino; idade média 46,0 ± 14,0 anos) com UCE que evolui há 129,7 ± 128,1 meses, tratados com ciclosporina numa dose média de 3,2 ± 0,3 mg/kg. Em 10 doentes (44%) observou-se boa resposta logo no primeiro mês com redução significativa do UAS7 (UAS7 ≤ 6) relativamente aos não respondedores (p < 0,05). Ocorreram eventos adversos em oito doentes, com necessidade de suspensão em seis (hipertensão arterial não controlada ou infeções). Nenhum dos dados avaliados mostrou relação com a resposta terapêutica.Conclusão: A ciclosporina, eficaz em 44% dos doentes com urticária moderada a grave, poderá ser considerada alternativa ao omalizumab, quando este não está disponível, mas com monitorização estreita de eventos adversos.

Cyclosporine for the treatment of lupus nephritis in patients with systemic lupus erythematosus.

This study aimed to assess retrospectively the efficacy and safety of cyclosporin A (CsA) therapy in patients with lupus nephritis (LN). From September 2005 to August 2015, eligible patients with LN undergoing CsA treatment were enrolled in the study. Medical charts as well as clinical and laboratory data were retrospectively reviewed. The data were evaluated at 0, 1, 6, 12 month(s) after the start of CsA. Serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine protein/creatinine ratio (uPCR), complement components C3, C4, and anti-double stranded DNA antibody (anti-dsDNA) titers were recorded. Renal response to CsA (complete response (CR) and partial response (PR)) and relapse after stopping CsA were set as primary endpoint, and adverse events, progression to end-stage renal disease (ESRD), and all-cause mortality as secondary endpoint. Among 60 patients enrolled, 11.7%, 20%, 25% achieved CR and 65.0%, 51.7%, 40% achieved PR at 1, 6, and 12 months, respectively. The SCr and eGFR remained stable during follow-up. After 1 year, CsA led to a decrease in median uPCR (3.79 to 0.51, p<0.001) and anti-dsDNA (10.1 to 5.7IU/mL, p=0.011), an increase in mean C3 (75.9 to 88.5mg/dL, p<0.001) and C4 (15.9 to 19.5mg/dL, p<0.001) as well as a decrease in glucocorticoid dose. There were no deaths or progression to ESRD originating from adverse events in our study. CsA is an effective and safe treatment for patients with LN. Further randomized controlled trials are needed. .

Topical ocular 0.1% cyclosporine A cationic emulsion in dry eye disease patients with severe keratitis: experience through the French early-access program.

PurposeThe objective of this study was to report the evaluation of efficacy and safety of cyclosporine A cationic emulsion (CsA CE) 0.1% for the treatment of severe keratitis in adults with dry eye disease (DED) in a French early-access program.MethodsPatients with DED and severe keratitis (corneal fluorescein staining [CFS] score of 3–5 on the Oxford scale and/or the presence of corneal lesions [filaments or ulcers]) were enrolled in a compassionate use program (Authorization for Temporary Use [ATU]) for once-daily CsA CE, which was approved by French health authorities prior to its registration. Efficacy and safety at 1, 3, 6, and 12-month follow-up visits were evaluated.ResultsThe ATU cohort (n=1,212; mean age =60.5 years; 79.5% female; 98.1% with severe keratitis; 74.5% with corneal lesions) consisted of 601 CsA-naïve patients and 611 patients treated previously with other CsA formulations. The primary DED etiology was Sjögren’s syndrome (48.7%). Clinical benefit could be discerned among 548 evaluable patients from months 1 to 12: keratitis improvement, 44.8% at month 1 and 42.1% at month 12; keratitis stabilization, 47.2% and 45.7%, respectively; symptom improvement, 47.2% and 48.6%; and symptom stabilization, 44.8% and 45.0%. Corneal clearing (CFS score =0) increased from 4.8% (month 1) to 11.4% (month 12). No unexpected safety concerns were identified; instillation site pain (10.2%) and eye irritation (7.8%) were the most common adverse events.ConclusionThe French ATU cohort provides supportive data on the clinical benefit of CsA CE in improving/stabilizing symptoms and corneal damage in DED patients with severe keratitis in real-world clinical practice.

Comparative evaluation of efficacy and safety of cyclosporine 0.1% add-on therapy with artificial tears (carboxymethylcellulose 0.5%) with artificial tears alone in post cataract surgery patients

Background: Cataract is the most common cause of preventable blindness and to surgically remove the affected lens and replace it with an artificial lens is the only effective treatment. Most patients post cataract surgery, complain of dry eye. Artificial tears are commonly used symptomatic treatment in dry eye. Since there is an underlying inflammatory cause; therefore, recently topical immunomodulator therapy is gaining acceptance. Aims and Objective: The present prospective, randomized, open-label, the study was undertaken to evaluate the efficacy of cyclosporine 0.1% as add-on therapy with artificial tears (carboxymethylcellulose 0.5%) in post cataract surgery patients suffering from moderate-to-severe dry eye symptoms. Materials and Methods: A total of 69 patients were selected after application of inclusion and exclusion criteria with 37 patients in artificial tears 0.5% group and 32 patients in cyclosporine 0.1% + artificial tears 0.5% group, respectively. Patients were followed up to 8 weeks. Grading of the severity of dry eye was done on the basis of ocular surface disease index scale (OSDI), and patients with >23 score were selected for the study. Safety and tolerability were based on adverse events reported by the participants. Results: Treatment in both the group’s cyclosporine 0.1% + artificial tears 0.5% and artificial tears 0.5% leads to a significant improvement in the OSDI score in the patients at 4 weeks and 8 weeks interval (P < 0.0001). On intergroup comparison, the effect on OSDI score was more favorably affected by combination therapy than artificial tears alone. Both treatments were well tolerated, itching/burning and redness were common adverse drug events, all the events reported were mild in nature and did not warrant any cessation of therapy or change of therapy. Conclusion: Cyclosporine 0.1% + artificial tears 0.5% and artificial tears 0.5% topical therapy caused improvement in moderate-to-severe dry eye condition. However, combination treatment was more effective than artificial tears alone, therefore, suggesting its clinical superiority in the improvement of overall symptoms of dry eye in the patients after cataract surgery.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989–2013): A Nationwide Multicenter Study

To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Low dose Cyclosporin A treatment increases live birth rate of unexplained recurrent abortion - initial cohort study

Pregnancy is similar to allogeneic transplantation. Eighty percent of unexplained recurrent spontaneous abortions (URSA) relate to disturbances of immune regulation. Cyclosporin A (CsA) is a immunosuppressant widely used after organ transplantation and to treat autoimmune disease. Animal studies show that low dose of CsA could induce maternal-fetal immunity tolerance while enhance trophoblast invasion. So far no clinical trial reported on the effect and safety of cyclosporin A treatment for URSA has been published. The objective of this study was to explore the effect, safety, and mechanism of low-dose CsA treatment in human patients in order to find a novel therapy to treat URSA. Eighty-six patients with eligible URSA treated at the clinic of the present hospital were included in this study from December 2009 to December 2012. The research was approved by the Ethics committee. Through a clinical study with prospective non-randomized controlled trials, the patients were divided into CsA treatment group (n = 66 cases) and in control group (n = 20 cases) based on the patients' choice. Both groups started treatment as soon as the pregnancy test was positive. Patients in the treatment group were treated with oral CsA 100 mg/day for 30 days. Patients in the control group were treated with progesterone 20 mg im per day until 12 weeks of gestation. Cytoimmunology test of CD3, CD4, CD8, CD4/8, CD4/25, CD19/21, and Th/Ts were examined before and after the treatment in both groups. Clinical consequences of mothers and fetuses were followed up and recorded. Live birth rate and cytoimmunology markers and their change before and after the treatment were analyzed and compared between the two groups. The live birth rate was significantly higher in study group (41/66, 62.1%) than in the control group (6/20, 30.0%) (p < 0.001). There was no obvious side effect and adverse consequence in the pregnancy women. No IUGR or birth defect was observed in fetus in this study. After CsA treatment, CD3 level in maternal blood was higher in successful group than abortion group but CD8 level was decreased after CsA treatment. Low-dose CsA treatment increases live birth rate of unexplained recurrent abortion. No maternal-fetal adverse consequence was observed in this study and it is safe in clinic use. The mechanism of CsA therapy may be related to immune regulation which may favor the success of pregnancy.

The efficacy of cyclosporine A as salvage therapy for severe active ulcerative colitis refractory to glucocorticoid

Objective: To clarify the efficacy and safety of cyclosporine A (CsA) as salvage therapy in patients with severe active ulcerative colitis (UC) and refractory to steroids. Methods: A total of 24 severe active UC patients refractory to steroids and hospitalized from 2006 to 2012, were retrospectively enrolled.Data including demographic features, clinical manifestations, laboratory tests and medications were collected. Results: CsA was effective in 15(62.5%) patients, who did not receive colectomy during 12-week administration. This regimen was tolerable in most patients.Twelve (50.0%) patients reported 16 adverse events, but only one patient withdrew CsA due to intolerance.The rates of adverse events in initial intravenous CsA including 4 mg·kg(-1)·d(-1,) 3 mg·kg(-1)·d(-1) and 2 mg·kg(-1)·d(-1) were 2/2, 9/17 and 1/5 respectively.Responders had higher white blood cell count compared with non-responders (P= 0.045). Conclusions: CsA could be an effective alternative regimen to colectomy in severe active UC patients who are refractory to steroids.

A Prospective, Randomized Study of Cyclosporine or Corticosteroids As an Adjunct to Plasma Exchange for the Treatment of Thrombotic Thrombocytopenic Purpura

INTRODUCTIONA prospective, randomized study (NCT00713193) was undertaken to compare the efficacy and safety of cyclosporine (CSA) and prednisone (P) as adjuncts to plasma exchange therapy (PEX) in the treatment of acquired TTP. The primary objective was to determine if CSA or P given as an adjunct to PEX has a lower exacerbation rate. Secondary endpoints included the effect of CSA and P on the ADAMTS13 activity and anti-ADAMTS13 antibody concentration and their relationship to clinical outcomes.METHODS: Patients were randomized 1:1 to CSA (2-3mg/kg/d orally) or P (1mg/kg/d orally) with daily PEX until response was achieved (normal platelets , LDH). After stopping PEX CSA was continued for 6 months; P was continued at full dose for the first 4 weeks, then tapered over 4 weeks. Exacerbation was defined as recurrent thrombocytopenia requiring PEX <30 days after the last PEX, with relapse defined as recurrence >30 days after the last PEX. ADAMTS13 biomarkers were obtained pretreatment, weekly for 4 weeks after the last PEX, monthly for 5 months, and then every 3 months until 42 months of follow-up.RESULTS: Since November 2007, 26 patients were randomized to CSA (n=12) or P (n=14) and followed for a median 42 m. (range, 1 -42). The study was halted after a planned interim analysis. Response rates were comparable in both arms (CSA: 11/12(92%); P:11/14,(79%);p=0.2), with one patient dying on each arm before achieving a response, and 2 P treated patients crossing over to the CSA arm after failing to achieve a response. The exacerbation rate on the CSA arm was 3/11(27%) v. 1/11(9%) on the P arm (p=0.3). Relapses in patients that achieved remission (without exacerbation) occurred in 5/8 CSA treated patients and 4/10 P treated patients at a median of 7 m. (range, 3-39) and 16m. (range, 4-26), respectively. Serial measurements of the ADAMTS13 activity and IgG inhibitor concentrations over the first 30 days after the last PEX and over the 6 m. CSA treatment course are show in Figures 1 and 2.CONCLUSIONS: There was no significant difference in the exacerbation rate between the CSA and P arms. However, improvement in the ADAMTS13 activity and suppression of the anti-ADAMTS13 antibodies were significantly better in the P arm compared to the CSA-treated patients. These ADAMTS13 activity and inhibitor concentration data for the first time provide support for the efficacy of P as an adjunct to PEX, and the superiority of P over CSA as an adjunct to PEX therapy in the initial treatment of acquired TTP. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Efficacy and Safety of Cyclosporin A in Pregnant Patients with Systemic Autoimmune Diseases

Cyclosporin A (CYS A) is an immunosuppressant agent administered in autoimmune diseases, and its use during pregnancy and lactation is a debated topic. The demographic characteristics, the activity of the underlying disease, and the onset of fetal-maternal complications have been investigated in 21 consecutive patients (2 RA, 14 SLE, 2 PA, 1 SjS, 1 DM, 1 Churg-Strauss vasculitis), treated with CYS A throughout 29 gestations. A subanalysis of the SLE group was performed. We recorded a live birth rate of 86.2%. The median gestational age at birth was 38.2 weeks. The prevalence of maternal-fetal complications showed no differences with general population. Disease flares appeared in 4% of patients during gestation and in 12% during puerperium. We found no evidence justifying the suspension of CYS A when a pregnancy occurs. The drug does not appear to promote maternal-fetal complications and should be continued in patients who benefit from therapy. Data regarding breast-feeding during therapy are still scarce, but no evidence of toxicity has emerged.

Cyclosporine A lipid nanoparticles for oral administration: Pharmacodynamics and safety evaluation

The pharmacodynamic effect and the safety of cyclosporine A lipid nanoparticles (CsA LN) for oral administration were investigated using Sandimmune Neoral® as reference. First, the biocompatibility of the unloaded LN on Caco-2 cells was demonstrated. The pharmacodynamic response and blood levels of CsA were studied in Balb/c mice after 5 and 10days of daily oral administration equivalent to 5 and 15mg/kg of CsA in different formulations. The in vivo nephrotoxicity after 15days of treatment at the high dose was also evaluated. The results showed a significant decrease in lymphocyte count (indicator of immunosuppression) for the CsA LN groups which was not observed with Sandimmune Neoral®. CsA blood levels remained constant over the time after treatment with LN, whereas a proportional increase in drug blood concentration was observed with Sandimmune Neoral®. Therefore, CsA LN exhibited a better pharmacological response along with more predictable pharmacokinetic information, diminishing the risk of toxicity. Moreover, a nephroprotective effect against CsA related toxicity was observed in the histopathological evaluation when LN containing Tween® 80 were administered. Therefore, our preliminary findings suggest LN formulations would be a good alternative for CsA oral delivery, enhancing efficacy and reducing the risk of nephrotoxicity.

Efficacy of cyclosporine A as monotherapy in patients with psoriatic arthritis: a subgroup analysis of the SYNERGY Study.

The SYNERGY Study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNERGY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexes of cutaneous and spinal involvement, PASI and BASDAI were significantly reduced over the study period, as were the number of swollen and tender peripheral joints, and enthesitis and dactylitis. Cyclosporine in monotherapy confirmed its efficacy in cutaneous psoriasis and suggested to be effective also on PsA, reducing spinal and peripheral joints' signs and symptoms.

Comparisons for Evaluation of Efficacy and Safety of Cyclosporin A 0.05% Ophthalmic Emulsion Treatment Groups

Comparisons for Evaluation of Efficacy and Safety of Cyclosporin A 0.05% Ophthalmic Emulsion Treatment Groups

Clinical experience with systemic cyclosporine A treatment in severe childhood psoriasis

Background: Severe forms of psoriasis including erythrodermic or pustular psoriasis, which require a more aggressive therapeutic approach such as phototherapy or systemic therapies, are rarely seen. Systemic toxicity and long-term safety of these agents are serious concerns in children. Objective: We report our experience on the efficacy and safety of cyclosporine A treatment in 22 patients of childhood psoriasis. Methods: We retrospectively analyzed the records of all patients less than 18 years of age treated with systemic cyclosporine A therapy at our clinic between January 2000 and March 2009. Demographic features as well as other relevant data including previous therapies, the dosage and duration of cyclosporine A therapy, response to treatment and side effects were retrieved from the patients’ records. Results: A total of 22 children were treated with systemic cyclosporine A therapy. Seventeen patients were found to be excellent responders. The mean therapeutic dosage of cyclosporine A was 3.47 ± 0.62 mg/kg/day. The mean duration of cyclosporine A therapy was 5.68 ± 3.29 months. The median time to total clearance of the lesions was 4.0 weeks. Conclusion: We conclude that cyclosporine A therapy is equally effective and safe in pediatric psoriasis patients as in adults.

Effectiveness and safety of cyclosporine in pediatric plaque psoriasis: A multicentric retrospective analysis

Background: Cyclosporine (CysA) is effective for psoriasis in adult patients but little data exist about its efficacy and safety in childhood and adolescence psoriasis. Objectives: To assess the effectiveness and safety of CysA for childhood and adolescence psoriasis. Methods: Retrospective analysis of a group of children and adolescents (age < 17 years) with plaque psoriasis treated with CysA at several Italian dermatology clinics. Results: Our study population consisted of 38 patients. The median age at the start of treatment was 12.3 years. Therapy duration varied from one to 36 months. The median maintenance dosage per day was 3.2 mg/kg (range 2–5 mg/kg). Fifteen patients (39,4%) achieved a complete clearance or a good improvement of their psoriasis defined by an improvement from baseline of ≥75% in the psoriasis area and severity index (PASI) at week 16. Eight patients (21.05%) discontinued the treatment due to laboratory anomalies or adverse events. Serious events were not recorded. Conclusions: In this case series, CysA was effective and well-tolerated treatment in a significant quote of children. CysA, when carefully monitored, may represent a therapeutic alternative to the currently used systemic immunosuppressive agents for severe childhood psoriasis.

In vivo release and retinal toxicity of cyclosporine-loaded intravitreal device

To determine the in vivo release profile and retinal safety of cyclosporine A (CsA) delivered from a biodegradable poly-lactide-co-glycolide (PLGA) device in the vitreous cavity of rabbits' eyes. A total of 60 animals (60 eyes) divided into two groups were used. For the in vivo release study, 32 eyes received PLGA implants containing 350 µg of CsA, and 16 eyes received the implants without drug (control). Four animals of CsA group and two of the control group were killed weekly until 8 weeks; the vitreous was removed, and CsA concentration was evaluated. Ophthalmological examination was performed in the animals prior to implant placement and weekly during the study period. Electroretinography (ERG) was performed in other six animals for each group, treated and control, at the beginning and at the end of the study (8 weeks) when they were killed and had their eyes processed for histology. No sign of inflammation was noticed on slit lamp examinations and the IOP maintained stable during the study period in CsA and control groups. CsA concentration in the vitreous (ng/ml) was 257.07 ± 117.23, 271.15 ± 98.96, 296.66 ± 86.25, 256.27 ± 99.22, 304.50 ± 88.18, 326.35 ± 105.24, 491.25 ± 119.90 and 589.93 ± 132.55 after 1, 2, 3, 4, 5, 6, 7 and 8 weeks of implantation, respectively. At the end of the study, 21.67 % of mass loss was found. The retina did not show any histological alteration in either group, but a significant reduction in dark-adapted b-wave amplitude was observed in the CsA group, with no changes in a-wave amplitude. These data show that the PLGA system is safe, but the selective reduction in ERG b-wave amplitude indicates that the PLGA with 350 µg CsA causes retinal function impairment, specifically on the rod postreceptor pathway, 8 weeks after implantation. These ERG changes were not associated with any histological damage as seen at the light microscopy level.

Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments.

Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.

Safety and Efficacy of Cyclosporine in Psoriatic Arthritis

Objectives The purpose of this study was to review evidence for the efficacy and safety of cyclosporine therapy in patients with psoriatic arthritis. Methods We performed a systematic literature review of available evidence using the electronic database PubMed. Results The available evidence suggests that cyclosporine may be an effective third-line treatment for psoriatic arthritis. However, its well-established side effect profile limits long-term use. Conclusion Cyclosporine may be an effective treatment option for psoriatic arthritis, but large randomized, placebo-controlled clinical trials with adequate sample sizes are needed to assess its impact on symptomatic control, inhibition of radiological disease progression, prevention of disability, and improvement of quality of life.

Barriers to the prescription of systemic therapies for moderate-to-severe psoriasis––a multinational cross-sectional study

Despite the availability of a plethora of approved systemic treatments, high proportions of patients with moderate-to-severe psoriasis do not receive systemic treatment. This study aims at identifying barriers that hinder dermatologists from prescribing systemic treatments for psoriasis. A cross-sectional online survey in six countries (Canada, Germany, Spain, France, Italy, UK) was performed among 300 dermatologists, assessing the relevance of 15 potential barriers towards prescribing acitretin, cyclosporine, methotrexate, adalimumab, etanercept, infliximab and ustekinumab. Multivariate regression analyses were used to explore provider characteristics related to these barriers. Treatment barriers are perceived differently in the countries investigated, with Spanish, Italian and Canadian dermatologists being particularly concerned about the safety of methotrexate and Canadian dermatologists about the safety of cyclosporine. In general, safety concerns were the most important barrier to the use of cyclosporine, (18% of participants' moderate/9% strong or very strong barrier). Costs were being perceived as a strong or very strong barrier to the use of the different biologics by 19-24% of the participants. Overall, country and work place were the most important determinants of treatment barriers. Sex, age, training, position and experience were minor determinants of treatment barriers. Medical reasons such as safety concerns or an inappropriate risk-benefit profile are particularly relevant barriers to the prescription of conventional treatments; whereas for biological treatments, economic reasons such as costs are more prevalent. Country specific analysis showed national differences in the perception of safety. The treatment barriers identified in this exploratory study should be confirmed in further health services research.

Cyclosporine in Anti-Jo1-positive Patients with Corticosteroid-refractory Interstitial Lung Disease

To describe the longterm effectiveness and safety of cyclosporine (CYC) in patients with anti-Jo1-positive antisynthetase syndrome with corticosteroid-refractory interstitial lung disease (ILD). All patients with anti-Jo1 antisynthetase syndrome referred to our division between June 1991 and February 2010 were retrospectively evaluated for ILD. ILD was assessed using pulmonary function tests (PFT) and/or high-resolution computed tomography (HRCT). Kazerooni score was used to evaluate the HRCT extent of ILD. Prednisone was the first-line treatment in all cases (1 mg/kg/day orally, then tapering). Patients with corticosteroid-refractory or relapsing ILD were then included in this retrospective study. All patients started CYC (3 mg/kg/day) without increasing prednisone dosage. Both PFT and chest HRCT were regularly reassessed during followup. Over the period of study we evaluated 18 patients with antisynthetase syndrome; 17 had ILD (13 women; median age at ILD onset 57 yrs); all patients failed prednisone within 12 months of ILD onset and subsequently started CYC. The median followup on CYC was 96 months [interquartile range (IQR) 57-120 mo]. Upon starting CYC, median forced vital capacity (FVC) was 60% (IQR 56%-70%), median DLCO 60% (IQR 50%-62.75%), and median Kazerooni score 16 (IQR 7-18). After 1 year of CYC, FVC (p = 0.0006), DLCO (p = 0.0010), and total Kazerooni score (p = 0.0002) improved and prednisone was tapered (median reduced from 25 mg/day to 2.5 mg/day; p < 0.0001). The results were substantially maintained including at last available followup. CYC side effects were hypertension (5 patients) and creatinine increase (6 patients). CYC was reduced in 3 cases and withdrawn in 4. Three out of 4 patients who interrupted CYC experienced ILD relapse; 2 patients recommenced low-dose CYC with subsequent ILD control. One patient refused re-treatment and subsequently died. CYC is effective and substantially safe in patients with anti-Jo1 antisynthetase syndrome with corticosteroid-refractory ILD. CYC withdrawal may be associated with ILD relapse, and low-dose CYC was effective in ILD control.