Comparison of Guidelines for the Use of Cyclosporine for Psoriasis: A Critical Appraisal and Comprehensive Review
March 2016 | Volume 15 | Issue 3 | Original Article | 293 | Copyright © 2016
Teo Soleymani MD,a Janna M. Vassantachart MS4,b and Jashin J. Wu MD FAADc
aThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY
bSchool of Medicine, Loma Linda University, Loma Linda, CA
cDepartment of Dermatology, Kaiser Permanente Los Angeles, Los Angeles, CA
There are several well-established guidelines for the treatment of psoriasis. Guidelines have been proposed in the United States by the American Academy of Dermatology (AAD), in Europe by the European S3, in the United Kingdom by the National Institute for Health and Care Excellence (NICE), and in Canada by the Canadian Dermatology Association. These guidelines are predominantly evidence-based, supported by expert panel consensus where evidence is lacking. Cyclosporine, a potent calcineurin inhibitor that acts selectively on T-cells, revolutionized the world of immunosuppression upon its discovery in 1970. Since its approval in 1997 by the U.S. Food and Drug Administration for the treatment of psoriasis, cyclosporine has been used with great efficacy in the treatment of not only psoriasis but also a wide consortium of dermatological diseases. However, in the past decade or so, many dermatologists have become increasingly
hesitant to use this important drug because of its potent toxicity profile.
The purpose of this article is to review and compare the current evidence-based guideline recommendations for the use of cyclosporine in the treatment of psoriasis.
Although the various guidelines are similar in their initial treatment recommendations, significant differences exist in recommendations on maximal treatment duration (1 year versus 2 years), intermittent short-term versus continuous therapy, use in erythrodermic and palmoplantar psoriasis, as well as recommendations on managing cyclosporine-associated side effects. By following guideline recommendations, cyclosporine remains an excellent and indispensable tool for the dermatologist treating moderate-to-severe psoriasis.
J Drugs Dermatol. 2016;15(3):293-301.
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Psoriasis is a common, chronic immune-mediated inflammatory skin disorder with potential systemic complications. Current epidemiological studies demonstrate a prevalence of 0.45-4.6% worldwide, with both ethnic and genetic factors strongly influencing incidence and prevalence.1-6 Although the complex pathogenesis of psoriasis remains incompletely understood, compelling evidence demonstrates that it is a systemic immune-mediated inflammatory disease in which CD-4+ T-lymphocytes play a key role in the production of pro-inflammatory cytokines and subsequent activation of inflammatory pathways.4-14 This results in a cascade of over-rampant inflammation that leads to clinically evident keratinocyte hyperproliferation and epidermal hyperplasia. Until recently, it was thought that psoriasis was predominantly TH-1 mediated, however eloquent research has illustrated that psoriasis is in fact primarily a disease driven by TH-17 cells and its respective cytokine IL-17.4-14
A landmark study published in the journal Lancet in 1978 demonstrated that cyclosporine was successful in preventing rejection in renal transplant patients who received mismatched kidneys.15 Just a year later in 1979, another milestone study was published, demonstrating cyclosporine’s ability to treat psoriasis.13 It was not until 18 years later in 1997, however, that cyclosporine was approved by the US FDA for the treatment of psoriasis. Since its initial discovery and approval, cyclosporine has continued to demonstrate excellent efficacy in the treatment of plaque-type psoriasis.16-26
Recommendations Prior to Initiating Therapy
The indications for cyclosporine are the same as any other systemic non-biologic treatment for psoriasis.17,23,25,26 Prior to initiation, patients should undergo a thorough history and physical examination, reviewing a history of severe infection including HIV, hepatitis B, or C, history of malignancy including cutaneous, renal or liver disease as well as current medications.17,23,25,26 Testing for TB should be considered and vaccinations should be up-to-date. Immunocompromised states such as HIV or cancer must be taken into serious consideration prior to starting cyclosporine.17,23 Patients should be evaluated for factors that may increase their risk of nephrotoxicity including diabetes, hypertension, obesity, age and concomitant use of nephrotoxic drugs.17,23,26 Reliable contraception is recommended for all patients of childbearing age.17,23,25,26 In addition, specific laboratory studies are strongly recommended prior to treatment initiation and are compared in Table 1.