Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2–3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9–9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1–21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.
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The purpose of this study is to propose a ranking system for the severity of psoriasis. The consensus method of selecting the indices to include and the classification of real patient profiles by an expert panel to create a gold standard of severity were used. The performance of potential cut-offs was evaluated to create a ranking algorithm. The combined use of PASI, BSA, and sPGA may allow the classification of the severity of psoriatic patients. The final algorithm identifies severe patients in a single step (2 out 3 are met: PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3), while two steps are required for mild ((2 out 3 are met: PASI ≤ 3 or BSA ≤ 5 or sPGA ≤ 2) and DLQI < 5) and moderate forms (the patient does not meet 2 out 3 (PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3) but has a DLQI ≥ 5. A ranking algorithm is presented, consisting of different measures of disease which classifies psoriatic patients into three categories: mild, moderate, and severe.
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