Cyclosporine In Psoriasis Research Articles

14393 Real world experience using cyclosporine in psoriasis: Efficacy and toxicity in the Australasian Psoriasis Registry

Background: Cyclosporine is a calcineurin inhibitor that is approved for short-term use to treat moderate to severe chronic plaque psoriasis. In Australia it is a requirement to have trialed and failed, or have a valid contraindication to, at least two of cyclosporine, methotrexate, acitretin, or nbUVB therapy to be eligible for subsidised biologic therapy for chronic plaque psoriasis in adults. Therefore, it is important in clinical practice throughout Australia that cyclosporine efficacy and safety is well understood.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

P3340Greater improvement of coronary artery function, left ventricular deformation and twisting by treatment with IL-17A antagonist compared to Cyclosporine in psoriasis

P3340Greater improvement of coronary artery function, left ventricular deformation and twisting by treatment with IL-17A antagonist compared to Cyclosporine in psoriasis

A pharmacogenetic study of ABCB1 polymorphisms and cyclosporine treatment response in patients with psoriasis in the Greek population.

Psoriasis affects 2-3% of the population, causing significant morbidity and financial burden. Immunosuppressive drugs such as cyclosporine are first line systemic therapies for moderate-to-severe forms. However, patients exhibit heterogeneity in their response to therapy, possibly due to genetic factors. The aim of the present study was to assess the ABCB1 T-129C, G1199A, C1236T, G2677T and C3435T single-nucleotide polymorphisms (SNPs) as candidate predictive markers of response to cyclosporine treatment in 84 psoriasis patients. 62% of the patients were defined as responders and 38% as nonresponders. All SNPs complied with Hardy-Weinberg equilibrium. SNP and haplotype analyses were performed to access responsiveness to treatment. Association analysis revealed statistically significant association of SNP 3435 T with negative response (P=0.0075), a result that was further validated in haplotype analysis. This study is the first in the field of the pharmacogenetics of cyclosporine in psoriasis whose results merit further exploitation in larger independent cohorts.

Combination of Etanercept and Twice-Weekly Administration of Cyclosporin in Psoriasis Unsatisfactorily Controlled by Etanercept Monotherapy: A Retrospective Analysis

Combination of systemic biological and traditional agents is increasingly used for the treatment of “high-need” patients with psoriasis. There are only limited data on the combination of cyclospori...

Evidence‐based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists

There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis. The aim of this study was to develop evidence-based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids. A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session. A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non-plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non-plaque psoriasis. These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.

Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non‐plaque psoriasis

Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words 'psoriasis', 'CyA', 'nephrotoxicity' during the period from 1980 to June 2010. The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2-4 months. CyA was more effective than etretinate on nail psoriasis. Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.

High Prevalence of Potential Drug-Drug Interactions for Psoriasis Patients Prescribed Methotrexate or Cyclosporine for Psoriasis: Associated Clinical and Economic Outcomes in Real-World Practice

High Prevalence of Potential Drug-Drug Interactions for Psoriasis Patients Prescribed Methotrexate or Cyclosporine for Psoriasis: Associated Clinical and Economic Outcomes in Real-World Practice

High Prevalence of Potential Drug-Drug Interactions for Psoriasis Patients Prescribed Methotrexate or Cyclosporine for Psoriasis: Associated Clinical and Economic Outcomes in Real-World Practice

Background: Methotrexate (MTX) and cyclosporine (CYC) may adversely interact with common medications in patients with psoriasis. Objective: Our purpose was to investigate the prevalence and outcomes of MTX/CYC polypharmacy. Methods: We evaluated rates of events that may be associated with drug-related toxicity, health care resource utilization and costs for patients with psoriasis in the Ingenix® Impact National Managed Care Database (1999–2007) who were exposed or not exposed to potential drug-drug interactions. Results: Among 4,583 (57.6%) exposed and 3,372 (42.4%) nonexposed patients, nonsteroidal anti-inflammatory drugs and antibiotics were the most common drugs with potential interactions. The exposed patients had significantly greater risks of developing renal [adjusted odds ratio (OR): 2.58; p = 0.0145], gastrointestinal (OR: 1.36; p = 0.0197) and pulmonary events (OR: 1.20; p = 0.0470), and significantly greater health care resource utilization (e.g. OR for inpatient and emergency department visits: 1.47; p < 0.0001) and costs (adjusted incremental cost: USD 1,722; p < 0.0001). Conclusions: MTX/CYC polypharmacy is prevalent in patients with psoriasis and associated with significant risks.

Understanding the Mechanism of Action of Methotrexate and Cyclosporine in Psoriasis

To uncover the mechanisms of action of two drugs successful in the treatment of psoriasis, researchers in the Netherlands investigated the effects of

Effect of pharmacologic treatment on dermatologic-specific quality of life (qol): a comparison of botulinum toxin type-a (bt-a) for primary focal hyperhidrosis (hh) to medical treatments for other dermatological diseases

Objectives: To review and compare via the Dermatology Life Quality Index (DLQI): 1) the effect of primary focal HH on QOL relative to other dermatological diseases; 2) the QOL treatment effect of BT-A for HH to the QOL treatment effect reported for other dermatological treatments and diseases.Methods: The DLQI is a 10 item dermatology-specific QOL questionnaire with a total score ranging from 0 to 30 (with 30 representing the worst impact on QOL). A literature search identified all publications reporting pre- and post-pharmacologic treatment DLQI scores for a variety of diseases. Using studies with data on at least 20 adult subjects to ensure sufficient sample size, an evidence table was constructed listing the pre- and post-pharmacologic DLQI score by dermatological disease and treatment. QOL treatment effect was defined as the reported mean or median difference in the pre- and post-treatment DLQI score.Results: 7 of 8 studies with pre- and post-pharmacologic treatment DLQI total scores reported data for at least 20 adult patients (3 on HH, 3 on moderate to severe psoriasis, and 1 on moderate to severe acne). Baseline DLQI total scores ranged from 9.1 to 18 for HH, 8.4 to 11.9 for psoriasis, and 8.3 to 9.2 for acne. Treatment effects ranged from −7.3 to −13 for BT-A in HH, −7 to −10 for cyclosporin in psoriasis, −2.4 to −6 for alefacept in psoriasis, and −5.8 to −6.1 for various treatments (oral isotretinoin, oral and topical antibiotics, and anti-androgens) in acne.Conclusion: The effect of primary focal hyperhidrosis on QOL as reported in the literature was similar to or greater than that reported at baseline for moderate to severe psoriasis and acne. In addition, the beneficial improvement in QOL reported for HH patients following the use of BT-A was similar to or greater than the magnitude of improvement in QOL reported for moderate to severe psoriasis following systemic treatment, and also was similar to or greater than the QOL benefit reported for moderate to severe acne following systemic and/or topical treatments. Objectives: To review and compare via the Dermatology Life Quality Index (DLQI): 1) the effect of primary focal HH on QOL relative to other dermatological diseases; 2) the QOL treatment effect of BT-A for HH to the QOL treatment effect reported for other dermatological treatments and diseases. Methods: The DLQI is a 10 item dermatology-specific QOL questionnaire with a total score ranging from 0 to 30 (with 30 representing the worst impact on QOL). A literature search identified all publications reporting pre- and post-pharmacologic treatment DLQI scores for a variety of diseases. Using studies with data on at least 20 adult subjects to ensure sufficient sample size, an evidence table was constructed listing the pre- and post-pharmacologic DLQI score by dermatological disease and treatment. QOL treatment effect was defined as the reported mean or median difference in the pre- and post-treatment DLQI score. Results: 7 of 8 studies with pre- and post-pharmacologic treatment DLQI total scores reported data for at least 20 adult patients (3 on HH, 3 on moderate to severe psoriasis, and 1 on moderate to severe acne). Baseline DLQI total scores ranged from 9.1 to 18 for HH, 8.4 to 11.9 for psoriasis, and 8.3 to 9.2 for acne. Treatment effects ranged from −7.3 to −13 for BT-A in HH, −7 to −10 for cyclosporin in psoriasis, −2.4 to −6 for alefacept in psoriasis, and −5.8 to −6.1 for various treatments (oral isotretinoin, oral and topical antibiotics, and anti-androgens) in acne. Conclusion: The effect of primary focal hyperhidrosis on QOL as reported in the literature was similar to or greater than that reported at baseline for moderate to severe psoriasis and acne. In addition, the beneficial improvement in QOL reported for HH patients following the use of BT-A was similar to or greater than the magnitude of improvement in QOL reported for moderate to severe psoriasis following systemic treatment, and also was similar to or greater than the QOL benefit reported for moderate to severe acne following systemic and/or topical treatments.

Concerns over the Present FDA Guidelines for the use of Cyclosporine in Psoriasis

Concerns over the Present FDA Guidelines for the use of Cyclosporine in Psoriasis

Renal function after 10 years' treatment with cyclosporin for psoriasis.

Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.

乾せんにおけるエトレチナートからシクロスポリンへの切替え療法の検討

乾癬に対する経口治療薬であるエトレチナートからシクロスポリンへの切替え療法の有効性と安全性を検討した。試験期間は最長20週とし, 乾癬患者にシクロスポリン2.5∼5mg/kg/日の投与をおこなった。総症例17例中エトレチナートからの切替え理由として, 無効または効果不十分が12例(70.6%)であった。シクロスポリン投与量は, 切替え時で平均2.6mg/kg/日, 最大投与量は平均3.2mg/kg/日で, 試験開始時に平均20.7であったPASIスコアが, シクロスポリン投与により4週後には平均10.0と有意な改善がみられた。寛解が得られた12週以降の平均投与量は2.7mg/kg/日で, シクロスポリン療法における寛解維持用量の目安になるものと考えられた。全般改善度は「著明改善」が得られた症例は9例(52.9%), また, 有用度では「極めて有用」の症例が8例(47.1%)であった。一方, 副作用発現症例率が41.2%(7/17例, 12件)と高い傾向を示したが, 内容は高血圧, 総ビリルビン上昇などいずれも軽度のもので, 投与量の漸減および中止により軽快した。以上からシクロスポリンはエトレチナートに抵抗性の症例に対しても高い有効性を示し, 有用な治療法であると考えられた。

Risk of cancer with cyclosporine in psoriasis.

Risk of cancer with cyclosporine in psoriasis.

Cyclosporin in psoriasis and dermatitis

Cyclosporin in psoriasis and dermatitis

Individualized short-course cyclosporin therapy in psoriasis.

The efficacy and side-effects of cyclosporin in psoriasis, namely hypertension and renal dysfunction, are dose-related. An initial dose of 3 mg/kg per day has a better risk/benefit ratio than 5 mg/kg per day. Maximum efficacy is usually reached after 2-3 months, and effects of the drug remain even after treatment stops. We therefore suggest that periodic short-term use of cyclosporin in order to combine persisting therapeutic effect with safety. Psoriatic erythroderma and arthropathy also respond rapidly to oral cyclosporin. Once patients have been successfully treated, the drug should be discontinued. Treatment must not exceed 6 months, but in the case of relapse a new cycle of the previously effective and tolerated dose can be given. The concomitant use of other therapies has been assessed in an attempt to reduce the dose of cyclosporin. There are no significant cyclosporin-sparing effects when etretinate or UVB are used adjunctively, and currently no convincing data on the risk of combining low-dose cyclosporin with immunosuppressive therapy (including methotrexate, UVB, and PUVA) in dermatological indications. The addition of topical corticosteroids or calcipotriol leads to more rapid clearing of psoriasis plaques, although relapse rates remain unchanged. Individualized short-course cyclosporin therapy is useful in controlling acute psoriasis flares and/or inducing remission; less potent agents can then be used for maintenance therapy. Short courses of low-dose cyclosporin may almost completely eliminate the risks of renal dysfunction from this drug.

Effects of cyclosporine on cytokines and cytokine receptors in psoriasis

Background: Oral cyclosporine is effective in the treatment of recalcitrant psoriasis. However, the precise mechanism(s) are not fully understood. A possible mode of action may be via down-modulation of proinflammatory cytokines that are increased in psoriatic lesions. Objective: This study was designed to monitor the effects of cyclosporine treatment on the expression of cytokines, cytokine receptors, and other markers of inflammation in psoriatic skin. Methods: Ten patients with recalcitrant psoriasis were treated with cyclosporine. The in vivo effects of cyclosporine on cytokines and their receptors were studied by the use of cryostatcut sections and a panel of antibodies. The in vitro effects were studied with flow cytometry of epidermal cell suspensions prepared from psoriatic lesions and control skin. Results: Clinical improvement was noted in all patients after 2 weeks of cyclosporine treatment. The expression of interleukin-1β, interleukin-8, CD25(IL-2R), CD36 and E-selectin were significantly decreased, whereas the number of tumor necrosis factor-receptor-positive epidermal cells was significantly increased in psoriatic lesions. Conclusion: Clinical improvement of psoriasis with cyclosporine treatment is accompanied by down modulation of proinflammatory epidermal cytokines and decreased dermal inflammation. Thus besides suppressing cytokine production by the inflammatory infiltrate, the beneficial effect of cyclosporine in psoriasis also depends on the inhibition of the epidermal cytokine network.

Short-contact anthralin treatment augments therapeutic efficacy of cyclosporine in psoriasis: A clinical and pathologic study

Background: Psoriasis is characterized by immune activation and increased epidermal proliferation. Cyclosporine acts by reducing T lymphocyte numbers and lymphokine production. Anthralin inhibits keratinocyte proliferation. Objective: We investigated whether topical anthralin would augment clearing of psoriasis produced by systemic cyclosporine. Methods: Twelve patients with psoriasis were treated with cyclosporine (5 mg/kg per day). Patients applied anthralin only to plaques on half of their body. They were treated until a remission or maximum benefit was achieved. Disease activity was assessed by a severity index and quantitative histopathologic markers. Results: Of the 12 patients, the skin of five cleared within 10 weeks irrespective of anthralin use. The other seven (slow responders) continued treatment for a mean of 18 weeks. Slow responders had a significantly lower severity index, a thinner epidermis, fewer CD8 + cells, and fewer proliferating keratinocytes on the anthralin-treated side than on the non-anthralin-treated side. Conclusion: The combination of cyclosporine and topical anthralin is effective in patients who are slow to respond to cyclosporine alone.

Individualized short-course cyclosporin therapy in psoriasis

The efficacy and side-effects of cyclosporin in psoriasis, namely hypertension and renal dysfunction, are dose-related. An initial dose of 3 mg/kg per day has a better risk/benefit ratio than 5 mg/kg per day. Maximum efficacy is usually reached after 2-3 months, and effects of the drug remain even after treatment stops. We therefore suggest that periodic short-term use of cyclosporin in order to combine persisting therapeutic effect with safety. Psoriatic erythroderma and arthropathy also respond rapidly to oral cyclosporin. Once patients have been successfully treated, the drug should be discontinued. Treatment must not exceed 6 months, but in the case of relapse a new cycle of the previously effective and tolerated dose can be given. The concomitant use of other therapies has been assessed in an attempt to reduce the dose of cyclosporin. There are no significant cyclosporin-sparing effects when etretinate or UVB are used adjunctively, and currently no convincing data on the risk of combining low-dose cyclosporin with immunosuppressive therapy (including methotrexate, UVB, and PUVA) in dermatological indications. The addition of topical corticosteroids or calcipotriol leads to more rapid clearing of psoriasis plaques, although relapse rates remain unchanged. Individualized short-course cyclosporin therapy is useful in controlling acute psoriasis flares and/or inducing remission; less potent agents can then be used for maintenance therapy. Short courses of low-dose cyclosporin may almost completely eliminate the risks of renal dysfunction from this drug.