1 days for patients with PASI scores selleck compound of 13 or more to 287.5 days for patients with PASI scores of <13. The PISCES study also compared the effects of abrupt against gradual discontinuation of CsA [6]. A total of 45% of subjects had not relapsed 4 months after stopping treatment, and 31% had not relapsed after 6 months. Median time to relapse was 109 days in the patients who abruptly stopped CsA and 113 days for patients who were tapered off. However, Hakkaart-van Roijen et al. [38] showed that gradually tapering the CsA dose before discontinuing treatment results in both lower costs and improved efficacy in comparison with abrupt discontinuation, improving the overall mean incremental cost-effectiveness ratio. These results corroborated previous findings showing better preservation of remission by drug tapering rather than abrupt discontinuation [13].

Longer-term continuous therapy may be required for maintenance in a minority of patients with recalcitrant disease, often with doses less than 3.5mg/kg/day [34]. However, renal dysfunction related to long-term CsA maintenance therapy is a major concern. While intermittent short courses are associated with dose-dependent, transient, and reversible renal function abnormalities, renal structural alterations have been demonstrated in a small percentage of patients after 2 years of continuous treatment at 5mg/kg/day [37, 39, 40]. Within this period, once the drug is withdrawn, the nephropathy is not progressive. For this reason, the US and European guidelines recommend to avoid continuous treatment for more than 1 year and 2 years, respectively [34, 40�C43].

Table 2 summarizes some of the most important studies exploring long-term management with CsA after induction of psoriasis remission (e.g., intermittent or continuous treatment strategies or maintenance treatment) [6, 12, 36, 37, 44�C47].Table 2Main studies with CsA after induction of remission in moderate-to-severe plaque-type psoriasis.4. Pulse Treatment Some studies explored the feasibility of CsA treatment as pulse administration for a few days per week for the induction or maintenance of psoriasis remission.4.1. For Induction of RemissionStarting from the premise of the 36-hour cell cycle of psoriatic keratinocytes, more than 20 years ago, Goodman et al. [48] studied the effects a new CsA regimen in 15 psoriasis patients, consisting in a 36-hour weekly schedule. This ��cell-cycle-derived dosing schedule�� was probably based on the traditional regimen with methotrexate for psoriasis. Carfilzomib In particular, CsA was administered at 12-hour intervals for three consecutive doses per week for 10 weeks. The initial dose was 2.5mg/kg/dose and was then increased every 2 weeks by 2.