Efficacy and safety of oral cyclosporin A (CyA; SandimmunR) for long-term treatment of chronic severe plaque psoriasis

Abstract

The value of oral cyclosporin A (CyA; Sandimmun) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation. The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2.5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the end-point was significantly higher in the group on 5.0 mg/kg/day (92%) than in that on 2.5 mg/kg/day (52%; P < 0.001). A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine > 30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine > 30% above baseline was dose-related. The results of this study show that 5.0 mg/kg/day of CyA is significantly more effective than 2.5 mg/kg/day in the treatment of chronic plaque psoriasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural Findings and Tumor Necrosis Factor-alpha and Intercellular Adhesion Molecule-1 Expression in Psoriasis Patients Before and After Oral Cyclosporin A Therapy

“…Efficacy of short-term, low-dose of Cy A in psoriasis is shown [22,23]. An initial dose of 5 mg=kg seems to be effective [24,25]. In our study a 3-to 7.5-mg=kg oral Cy A treatment for 6 months caused no complications in any of the patients.…”

Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials

“…68 Since our previous review, 14 a substantial number of new head-to-head trials comparing different pharmacological treatments for psoriasis against each other have been published. This is a very positive development highlighting that the Adalimumab 0Á065 (À0Á038 to 0Á168) Etanercept 2 9 50 mg 0Á235 (0Á140-0Á330) 0Á17 (0Á10-0Á24) 60 Etanercept 1 9 50 mg or 2 9 25 mg 0Á367 (0Á270-0Á464) CSA low dose (2Á5-3 mg) 0Á429 (0Á256-0Á602) Alefacept 0Á547 (0Á442-0Á652) MTX 0Á278 (À0Á211 to 0Á767) Ustekinumab 45 mg Adalimumab 0Á020 (À0Á048 to 0Á089) Etanercept 2 9 50 mg 0Á190 (0Á134-0Á246) 0Á11 (0Á03-0Á19) 60 Etanercept 1 9 50 mg or 2 9 25 mg 0Á322 (0Á264-0Á380) CSA low dose (2Á5-3 mg) 0Á384 (0Á229-0Á539) Alefacept 0Á502 (0Á430-0Á574) MTX 0Á233 (À0Á249 to 0Á716) Adalimumab Etanercept 2 9 50 mg 0Á170 (0Á100-0Á240) Etanercept 1 9 50 mg or 2 9 25 mg 0Á302 (0Á230-0Á374) CSA low dose (2Á5-3 mg) 0Á364 (0Á204-0Á524) Alefacept 0Á482 (0Á399-0Á565) MTX 0Á213 (À0Á271 to 0Á697) 0Á44 (0Á32-0Á56) 35 Etanercept high dose 2 9 50 mg Etanercept 1 9 50 mg or 2 9 25 mg 0Á132 (0Á072-0Á192) 0Á17 (0Á12-0Á22) 10,43,48,49 CSA low dose (2Á5-3 mg) 0Á194 (0Á038-0Á349) Alefacept 0Á312 (0Á239-0Á385) MTX 0Á043 (À0Á440 to 0Á526) Etanercept low dose 1 9 50 mg or 2 9 25 mg CSA low dose (2Á5-3 mg) 0Á062 (À0Á094 to 0Á218) Alefacept 0Á180 (0Á105 to 0Á255) MTX 0Á089 (À0Á394 to 0Á572) CSA high dose (5 mg) CSA low dose (2Á5-3 mg) 0Á35 (0Á20 to 0Á51) 20,24 CSA low dose (2Á5-3 mg) Alefacept 0Á118 (À0Á044 to 0Á280) MTX 0Á151 (À0Á353 to 0Á655) 0Á15 (À0Á01 to 0Á30) 23,25 Alefacept MTX 0Á269 (À0Á216 to 0Á754) MTX Fumaric acid 0Á05 (À0Á18 to 0Á27) 30 RD, risk difference, interpreted as the excess chance for PASI 75 response of intervention vs. comparator; CI, confidence interval; CSA, ciclosporin A; MTX, methotrexate. a Based on all placebo-controlled trials on the interventions included (see Fig.…”

Which Antipsoriatic Drug Has the Fastest Onset of Action?—Systematic Review on the Rapidity of the Onset of Action

“…During treatment with low-dose CsA, a period of 2.3 weeks was required for a 25% reduction and a period of 5.4 weeks was required for a 50% reduction in the mean PASI (8 study arms, n ¼ 359) Elder et al, 1995;Mahrle et al, 1995;Meffert et al, 1997;Heydendael et al, 2003;Yoon and Youn, 2007;Vena et al, 2012). Patients treated with high-dose CsA achieved a reduction in the mean PASI by 25% within a period of 1.6 weeks and a reduction in the mean PASI by 50% within a period of 3.1 weeks (4 study arms, n ¼ 211) (Finzi et al, 1993;Laburte et al, 1994;Reitamo et al, 2001;Yoon and Youn, 2007). Patients treated with low-dose etanercept (3 study arms, n ¼ 811) required time periods of 3.5 and 10.9 weeks to lower the mean PASI by 25% and 50%, respectively (Leonardi et al, 2003;Costanzo et al, 2005;van de Kerkhof et al, 2008).…”