Cyclosporine is an immunosuppressive polypeptide used to prevent graft versus host disease in stem cell transplant recipients and prevent graft rejection in solid organ transplant recipients. In addition, cyclosporine is used in the treatment of immune-mediated diseases, including psoriasis and rheumatoid arthritis.
Cyclosporine reduces production of interleukin (IL)-2 and other cytokines produced by T-lymphocytes via interaction with calcineurin. Cyclosporine should be considered for acute treatment of severe psoriasis and when other systemic medications have failed. Safety and efficacy of cyclosporine can be improved through education and adherence to strict periodic monitoring guidelines.
Mechanism of Action
Cyclosporine is a lipophilic cyclic peptide composed of 11 amino acids. The drug binds with high affinity to cyclophilins (a family of cytoplasmic proteins). This drug-receptor complex competitively inhibits calcineurin. Ultimately, the drug inhibits the translocation of NF-AT leading to decreased transcriptional activation of cytokine genes for IL-2, IL-3, IL-4, tumor necrosis factor-alpha, CD40L, GM-CSF, interferon gamma and reduction in lymphocyte proliferation. Cyclosporine specifically affects T-helper lymphocytes, T-suppressor lymphocytes and T-cytotoxic lymphocytes.
Dosing
Cyclosporine may be administered via various formulations including oral, intravenous (IV), topical and ophthalmic. However, the IV form is only used in extenuating circumstances due to increased risk of toxicity. Oral bioavailability of the drug is limited due to inadequate absorption, metabolism by enzymes in the bowel mucosa and first-pass effect in the liver. Cyclosporine is metabolized in the gut mucosa to a minimal extent and extensively by CYP-450 in the liver with excretion in the bile. Bile salts are necessary for the absorption of cyclosporine. Absorption may be increased with consumption of a fatty meal at the time of drug administration.
Development of microemulsion oral formulations allows absorption of the drug in the absence of bile salts and leads to increased drug bioavailability. Therefore, the microemulsion formulation is generally preferred, particularly in individuals with biliary diversion or cholestasis. Initial dosing of cyclosporine for psoriasis is 2.5 mg/kg to 4 mg/kg divided into 2 doses, sometimes somewhat higher for short periods to get rapid control of flaring psoriasis.
Efficacy
A meta-analysis of several randomized studies involving patients with severe psoriasis determined that after 10 to 12 weeks of cyclosporine treatment at 1.25 mg/kg/day, 2.5 mg/kg/day and 5 mg/kg/day, there were Psoriasis Area and Severity Index (PASI) reductions of 44.4%, 69.8% and 71.5% respectively. In a study which assessed severe psoriasis patients assigned to either a 2.5 mg/kg/day starting dose and an increasing regimen or a 5.0 mg/kg/day starting dose and a decreasing regimen, PASI 50 response rates at 12 weeks was similar for both groups, while PASI 75 response rate at 12 weeks was higher in the step-down regimen group.
Side Effects
Frequency and severity of side effects are less in patients using the drug for treatment of dermatological and autoimmune disorders versus usage in transplant recipients due to lower doses and more flexibility in decreasing medications if signs of side effects arise.
Nevertheless, the side effect profile of cyclosporine limits its use (Table 1). In some cases, side effects associated with cyclosporine may be reversible upon discontinuation of use.
Contraindications
Absolute contraindications to use of cyclosporine include malignancy, uncontrolled hypertension, renal insufficiency, uncontrolled infection, immune deficiency, high cumulative dose of previous psoralen and UVA light phototherapy, cutaneous T cell lymphoma and hypersensitivity to cyclosporine (Table 2). Due to the immunosuppressive effects of cyclosporine, it is prudent to inquire about the presence of these contraindications in a patient being considered for cyclosporine therapy.
Monitoring
Various recommended monitoring guidelines exist to assist healthcare providers in monitoring for potential side effects of cyclosporine therapy (Table 3). At each office visit, patients should be asked questions pertaining to common side effects of cyclosporine use.
Malignancy screening guidelines include colonoscopy, mammogram, Pap smear, etc. Due to the gingival hyperplasia side effect, patients on cyclosporine should be instructed to visit the dentist at 6-month intervals. Age-appropriate vaccinations should be obtained prior to starting cyclosporine therapy. The pneumococcal vaccine should be administered once, and killed influenza vaccinations should be administered annually.
Tips and Tricks
1. The use of cyclosporine should be limited to short time periods where a quick improvement in severe psoriasis is necessary.
2. Avoid using cyclosporine for more than 2 years, as this increases the chance of kidney failure. Biologic medications are much safer options in patients with severe disease necessitating systemic treatment.
This article is an excerpt from the book, Practical Psoriasis Management.
Ms. Cardwell is PGY-1 in internal medicine with Medical College of Wisconsin Affiliated Hospitals in Milwaukee, WI.
Dr. Anderson is with Wake Forest Baptist Health Department of Dermatology in Winston-Salem, NC.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Yoon HS, Youn JI. A comparison of two cyclosporine dosage regimens for the treatment of severe psoriasis. J Dermatolog Treat 2007;18(5):286-290.
2. Colombo MD, Cassano N, Bellia G, Vena GA. Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. ScientificWorld Journal. 2013;2013:805705.
Cyclosporine is an immunosuppressive polypeptide used to prevent graft versus host disease in stem cell transplant recipients and prevent graft rejection in solid organ transplant recipients. In addition, cyclosporine is used in the treatment of immune-mediated diseases, including psoriasis and rheumatoid arthritis.
Cyclosporine reduces production of interleukin (IL)-2 and other cytokines produced by T-lymphocytes via interaction with calcineurin. Cyclosporine should be considered for acute treatment of severe psoriasis and when other systemic medications have failed. Safety and efficacy of cyclosporine can be improved through education and adherence to strict periodic monitoring guidelines.
Mechanism of Action
Cyclosporine is a lipophilic cyclic peptide composed of 11 amino acids. The drug binds with high affinity to cyclophilins (a family of cytoplasmic proteins). This drug-receptor complex competitively inhibits calcineurin. Ultimately, the drug inhibits the translocation of NF-AT leading to decreased transcriptional activation of cytokine genes for IL-2, IL-3, IL-4, tumor necrosis factor-alpha, CD40L, GM-CSF, interferon gamma and reduction in lymphocyte proliferation. Cyclosporine specifically affects T-helper lymphocytes, T-suppressor lymphocytes and T-cytotoxic lymphocytes.
Dosing
Cyclosporine may be administered via various formulations including oral, intravenous (IV), topical and ophthalmic. However, the IV form is only used in extenuating circumstances due to increased risk of toxicity. Oral bioavailability of the drug is limited due to inadequate absorption, metabolism by enzymes in the bowel mucosa and first-pass effect in the liver. Cyclosporine is metabolized in the gut mucosa to a minimal extent and extensively by CYP-450 in the liver with excretion in the bile. Bile salts are necessary for the absorption of cyclosporine. Absorption may be increased with consumption of a fatty meal at the time of drug administration.
Development of microemulsion oral formulations allows absorption of the drug in the absence of bile salts and leads to increased drug bioavailability. Therefore, the microemulsion formulation is generally preferred, particularly in individuals with biliary diversion or cholestasis. Initial dosing of cyclosporine for psoriasis is 2.5 mg/kg to 4 mg/kg divided into 2 doses, sometimes somewhat higher for short periods to get rapid control of flaring psoriasis.
Efficacy
A meta-analysis of several randomized studies involving patients with severe psoriasis determined that after 10 to 12 weeks of cyclosporine treatment at 1.25 mg/kg/day, 2.5 mg/kg/day and 5 mg/kg/day, there were Psoriasis Area and Severity Index (PASI) reductions of 44.4%, 69.8% and 71.5% respectively. In a study which assessed severe psoriasis patients assigned to either a 2.5 mg/kg/day starting dose and an increasing regimen or a 5.0 mg/kg/day starting dose and a decreasing regimen, PASI 50 response rates at 12 weeks was similar for both groups, while PASI 75 response rate at 12 weeks was higher in the step-down regimen group.
Side Effects
Frequency and severity of side effects are less in patients using the drug for treatment of dermatological and autoimmune disorders versus usage in transplant recipients due to lower doses and more flexibility in decreasing medications if signs of side effects arise.
Nevertheless, the side effect profile of cyclosporine limits its use (Table 1). In some cases, side effects associated with cyclosporine may be reversible upon discontinuation of use.
Contraindications
Absolute contraindications to use of cyclosporine include malignancy, uncontrolled hypertension, renal insufficiency, uncontrolled infection, immune deficiency, high cumulative dose of previous psoralen and UVA light phototherapy, cutaneous T cell lymphoma and hypersensitivity to cyclosporine (Table 2). Due to the immunosuppressive effects of cyclosporine, it is prudent to inquire about the presence of these contraindications in a patient being considered for cyclosporine therapy.
Monitoring
Various recommended monitoring guidelines exist to assist healthcare providers in monitoring for potential side effects of cyclosporine therapy (Table 3). At each office visit, patients should be asked questions pertaining to common side effects of cyclosporine use.
Malignancy screening guidelines include colonoscopy, mammogram, Pap smear, etc. Due to the gingival hyperplasia side effect, patients on cyclosporine should be instructed to visit the dentist at 6-month intervals. Age-appropriate vaccinations should be obtained prior to starting cyclosporine therapy. The pneumococcal vaccine should be administered once, and killed influenza vaccinations should be administered annually.
Tips and Tricks
1. The use of cyclosporine should be limited to short time periods where a quick improvement in severe psoriasis is necessary.
2. Avoid using cyclosporine for more than 2 years, as this increases the chance of kidney failure. Biologic medications are much safer options in patients with severe disease necessitating systemic treatment.
This article is an excerpt from the book, Practical Psoriasis Management.
Ms. Cardwell is PGY-1 in internal medicine with Medical College of Wisconsin Affiliated Hospitals in Milwaukee, WI.
Dr. Anderson is with Wake Forest Baptist Health Department of Dermatology in Winston-Salem, NC.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Yoon HS, Youn JI. A comparison of two cyclosporine dosage regimens for the treatment of severe psoriasis. J Dermatolog Treat 2007;18(5):286-290.
2. Colombo MD, Cassano N, Bellia G, Vena GA. Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. ScientificWorld Journal. 2013;2013:805705.
Cyclosporine is an immunosuppressive polypeptide used to prevent graft versus host disease in stem cell transplant recipients and prevent graft rejection in solid organ transplant recipients. In addition, cyclosporine is used in the treatment of immune-mediated diseases, including psoriasis and rheumatoid arthritis.
Cyclosporine reduces production of interleukin (IL)-2 and other cytokines produced by T-lymphocytes via interaction with calcineurin. Cyclosporine should be considered for acute treatment of severe psoriasis and when other systemic medications have failed. Safety and efficacy of cyclosporine can be improved through education and adherence to strict periodic monitoring guidelines.
Mechanism of Action
Cyclosporine is a lipophilic cyclic peptide composed of 11 amino acids. The drug binds with high affinity to cyclophilins (a family of cytoplasmic proteins). This drug-receptor complex competitively inhibits calcineurin. Ultimately, the drug inhibits the translocation of NF-AT leading to decreased transcriptional activation of cytokine genes for IL-2, IL-3, IL-4, tumor necrosis factor-alpha, CD40L, GM-CSF, interferon gamma and reduction in lymphocyte proliferation. Cyclosporine specifically affects T-helper lymphocytes, T-suppressor lymphocytes and T-cytotoxic lymphocytes.
Dosing
Cyclosporine may be administered via various formulations including oral, intravenous (IV), topical and ophthalmic. However, the IV form is only used in extenuating circumstances due to increased risk of toxicity. Oral bioavailability of the drug is limited due to inadequate absorption, metabolism by enzymes in the bowel mucosa and first-pass effect in the liver. Cyclosporine is metabolized in the gut mucosa to a minimal extent and extensively by CYP-450 in the liver with excretion in the bile. Bile salts are necessary for the absorption of cyclosporine. Absorption may be increased with consumption of a fatty meal at the time of drug administration.
Development of microemulsion oral formulations allows absorption of the drug in the absence of bile salts and leads to increased drug bioavailability. Therefore, the microemulsion formulation is generally preferred, particularly in individuals with biliary diversion or cholestasis. Initial dosing of cyclosporine for psoriasis is 2.5 mg/kg to 4 mg/kg divided into 2 doses, sometimes somewhat higher for short periods to get rapid control of flaring psoriasis.
Efficacy
A meta-analysis of several randomized studies involving patients with severe psoriasis determined that after 10 to 12 weeks of cyclosporine treatment at 1.25 mg/kg/day, 2.5 mg/kg/day and 5 mg/kg/day, there were Psoriasis Area and Severity Index (PASI) reductions of 44.4%, 69.8% and 71.5% respectively. In a study which assessed severe psoriasis patients assigned to either a 2.5 mg/kg/day starting dose and an increasing regimen or a 5.0 mg/kg/day starting dose and a decreasing regimen, PASI 50 response rates at 12 weeks was similar for both groups, while PASI 75 response rate at 12 weeks was higher in the step-down regimen group.
Side Effects
Frequency and severity of side effects are less in patients using the drug for treatment of dermatological and autoimmune disorders versus usage in transplant recipients due to lower doses and more flexibility in decreasing medications if signs of side effects arise.
Nevertheless, the side effect profile of cyclosporine limits its use (Table 1). In some cases, side effects associated with cyclosporine may be reversible upon discontinuation of use.
Contraindications
Absolute contraindications to use of cyclosporine include malignancy, uncontrolled hypertension, renal insufficiency, uncontrolled infection, immune deficiency, high cumulative dose of previous psoralen and UVA light phototherapy, cutaneous T cell lymphoma and hypersensitivity to cyclosporine (Table 2). Due to the immunosuppressive effects of cyclosporine, it is prudent to inquire about the presence of these contraindications in a patient being considered for cyclosporine therapy.
Monitoring
Various recommended monitoring guidelines exist to assist healthcare providers in monitoring for potential side effects of cyclosporine therapy (Table 3). At each office visit, patients should be asked questions pertaining to common side effects of cyclosporine use.
Malignancy screening guidelines include colonoscopy, mammogram, Pap smear, etc. Due to the gingival hyperplasia side effect, patients on cyclosporine should be instructed to visit the dentist at 6-month intervals. Age-appropriate vaccinations should be obtained prior to starting cyclosporine therapy. The pneumococcal vaccine should be administered once, and killed influenza vaccinations should be administered annually.
Tips and Tricks
1. The use of cyclosporine should be limited to short time periods where a quick improvement in severe psoriasis is necessary.
2. Avoid using cyclosporine for more than 2 years, as this increases the chance of kidney failure. Biologic medications are much safer options in patients with severe disease necessitating systemic treatment.
This article is an excerpt from the book, Practical Psoriasis Management.
Ms. Cardwell is PGY-1 in internal medicine with Medical College of Wisconsin Affiliated Hospitals in Milwaukee, WI.
Dr. Anderson is with Wake Forest Baptist Health Department of Dermatology in Winston-Salem, NC.
Dr. Feldman is with the Center for Dermatology Research and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine in Winston-Salem, NC.
Disclosure: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec and Bristol-Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea and Anacor and has received stock options from Photomedex. He is owner of www.DrScore.com and a founder of Causa Research.
Disclosure: The authors report no relevant financial relationships.
Suggested References
1. Yoon HS, Youn JI. A comparison of two cyclosporine dosage regimens for the treatment of severe psoriasis. J Dermatolog Treat 2007;18(5):286-290.
2. Colombo MD, Cassano N, Bellia G, Vena GA. Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. ScientificWorld Journal. 2013;2013:805705.
