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doi: 10.1111/j.1365-2133.1996.tb00701.xpmid: 8881896
SummaryCyclosporin is a highly effective treatment for psoriasis, atopic dermatitis and many other inflammatory dermatoses. Absorption of cyclosporin from the traditional Sandimmun® formulation is influenced by many factors, including bile flow, food and gastrointestinal motility. As a consequence, the bioavailability of Sandimmun® is low and highly variable, both within and between patients. Neoral® is a microemulsion preconcentrate formulation that has self‐emulsifying properties and immediately forms a microemulsion in aqueous fluids, allowing rapid and consistent absorption of cyclosporin from the gastrointestinal tract. Benefits in dermatology are likely to be more patients responding at lower doses, a faster onset of action and a more predictable response to a given dose allowing for fewer dose adjustments. In the future these benefits of Neoral® may lead to the simplified management of cyclosporin treatment and less frequent safety monitoring.
doi: 10.1111/j.1365-2133.1996.tb00702.xpmid: 8881897
SummaryCyclosporin has been shown to be highly effective in psoriasis, atopic dermatitis and numerous other dermatoses. Depite the effectiveness of cyclosporin, the response varies somewhat between individuals. Some may not respond, and often this is linked with unpredictable absorption of the traditional formulation. Cases of atopic dermatitis and psoriasis previously resistant to cyclosporn have responded wel to a new microemulsified formulation, Neoral®, and formal trials are now underway to investiage its use in these indications. Preliminary data from a clinical trial using the new traditional formulation in this condition, and that repeated short courses of therapy may be well tolerated.
CHAWLA, M.; ALI, M.; MARKS, R.
doi: 10.1111/j.1365-2133.1996.tb00703.xpmid: 8881898
SummaryA comparison was made of the efficacy, tolerability, safety and steady state pharmacokinetics of Sandimmun® in 11 stable atopic dermatitis patients already on Sandimmun®. The study was of an open, crossover design. At entry into the trial, patients were switched to Neoral® for 28 days. Treatment was switched back to Sandimmun® for Days 28 to 42. The morning dose was given fasting, the evening dose after a standard meal. Al measures of eczema severity improved during the Neoral® treatment period. Neoral® was markedly better tolerated with fewer side‐effects. Switching from Sandimmun® to Neoral® at the same dose resulted in less variable pharmacokinetic profiles in both fasted and fed states. There was an increase in bioavailability with better, less variable and faster absorption, with a slightly reduced tmax, a higher mean Cmax (+43%) and a higher mean AUC (+30%) in fasted, but not fed patients. Higher trough levels (Cmin) occurred throughout for Neoral® These differences between the two formulations were not associated with any changes in safety parameters. Overall, Neoral® was equivalent or superior to Sandimmun® in tolerability and efficacy when given on a 1:1 dose basis.
ZONNEVELD, I.M.; DE RIE, M.A.; BELJAARDS, R.C.; VAN DER RHEE, H.J.; WUITE, J.; ZEEGELAAR, J.; BOS, J.D.
doi: 10.1111/j.1365-2133.1996.tb00704.xpmid: 8881899
SummaryAn open, randomized trial was performed to determine the optimal dosage schedule with regard to the efficacy and safety of cyclosporin in severe atopic dermatitis. The study also provided clinical experience with regard to the efficacy and safety of long‐term cyclosporin treatment. During a 2‐month dose‐finding period. 78 patients with severe, long‐standing atopic dermatitis received cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B). Patients were maintained on their optimal dose for a further 10 months. Patients in Group A showed a significantly greater improvement in efficacy parameters over the first 2 weeks than with patients in Group B, but as the dose was decreased in Group A and increased in Group B, these differences were minimized. After 1 year, cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed by a severity score. Assessed in terms of an area score, these figures were 48.7% and 40%, respectively. Cyclosporin demonstrated a good safety profile during long‐term treatment and was generally well tolerated. The lower starting dosage was not associated with higher dropout rates. This study showed no differences in efficacy or adverse events between the two dosage schedules in long‐term treatment.
ZAKI, I.; EMERSON, R.; ALLEN, B.R.
doi: 10.1111/j.1365-2133.1996.tb00705.xpmid: 8881900
SummaryCyclosporin has been shown to be effective in the treatment of adult atopic dermatitis, but there are no clinical trials evaluating its use in childhood. Atopic dermatitis is more common in children and the severe form can be associated with considerable morbidity. We report on 18 children with severe refractory atopic dermatitis who have been treated with cyclosporin on an open basis. The drug was given at an initial daily dose of 5 or 6 mg/kg and in some patients the dose was reduced according to response. Sixteen patients showed a good or excellent response to treatment, one a moderate response and one patient failed to improve. The treatment was well tolerated and there were no significant changes in serum creatinine or blood pressure. Long remission after withdrawal of treatment was seen in some patients, although most relapsed within a few weeks. We suggest that cyclosporin is an effective and safe short‐term treatment for severe atopic dermatitis in childhood.
doi: 10.1111/j.1365-2133.1996.tb00706.xpmid: 8881901
SummaryThe Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple and effective system for recording and monitoring disease activity in atopic dermatitis. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of 0 (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, trunk. The maximum score is 108.
doi: 10.1111/j.1365-2133.1996.tb00707.xpmid: 8881902
SummaryThe efficacy and side‐effects of cyclosporin in psoriasis, namely hypertension and renal dysfunction, are dose‐related. An initial dose of 3 mg/kg per day has a better risk/benefit ratio than 5 mg/kg per day. Maximum efficacy is usually reached after 2–3 months, and effects of the drug remain even after treatment stops. We therefore suggest the periodic short‐term use of cyclosporin in order to combine persisting therapeutic effect with safety. Psoriatic erythroderma and arthropathy also respond rapidly to oral cyclosporin. Once patients have been successfully treated, the drug should be discontinued. Treatment must not exceed 6 months, but in the case of relapse, a new cycle of the previously effective and tolerated dose can be given. The concomitant use of other therapies has been assessed in an attempt to reduce the dose of cyclosporin. There are no significant cyclosporin‐sparing effects when etretinate or UVB are used adjunctively, and currently no convincing data on the risk of combining low‐dose cyclosporin with immunosuppressive therapy (including methotrexate, UVB. and PUVA) in dermatological indications. The addition of topical corticosteroids or calcipotriol leads to more rapid clearing of psoriasis plaques, although relapse rates remain unchanged. Individualized short‐course cyclosporin therapy is useful in controlling acute psoriasis flares and/or inducing remission; less potent agents can then be used for maintenance therapy. Short courses of low‐dose cyclosporin may almost completely eliminate the risks of renal dysfunction from this drug.
GULLIVER, W.P.; MURPHY, G.F.; HANNAFORD, V.A.; PRIMMETT, D.R.N.
doi: 10.1111/j.1365-2133.1996.tb00708.xpmid: 8881903
SummaryCyclosporin, as the microemulsion formulation Neoral®, was given to two groups of patients with severe psoriasis (Psoriasis Area and Severity Index: PASI > 12.0). Group A (10 patients) were receiving the traditional formulation of cyclosporin, Sandimmun®, at the start of the study, with a partial clinical response, and were switched to Neoral® at the same dose (3.3 mg/kg per day). Group B patients, who had previously been treated with Sandimmun® but were treatment failures, were given Neoral®, 3.5 mg/kg per day. This led to rapid improvement in psoriasis in both groups. In Group A mean PASI fell from 22.3 to 11.6 on Sandimmun®, after 82 ± 30 weeks, and to 4.0 (P<0.05) after 32 weeks of Neoral®. In Group B mean PASI decreased from 20.3 to 3.7 (P < 0.05) at a dose of 3.1 mg/kg per day. Pharmacokinetic data demonstrated significant decrease in tmax from 2.3 to 1.4 hours. After 2 weeks Cmax and the area under the curve (AUC) (0–4h) were significantly increased by 41% and 61%, respectively. Further pharmacokinetic data at 3 months showed similar results. No significant changes in renal function from pre‐treatment status were seen in either group. None of the patients developed hypertension. No serious adverse events were reported. The microemulsion formulation of cyclosporin showed greater efficacy and bioavailability. Improved outcome was seen at doses which were on average 15% lower than with the traditional formulation, leading to a reduction in cost of treatment.
doi: 10.1111/j.1365-2133.1996.tb00709.xpmid: 8881904
SummaryCyclosporin represents a major step forward in the systemic treatment of various dermatoses. Psoriasis vulgaris and atopic eczema, the two major indications for the drug, are dealt with elsewhere in this issue. Therefore, this short review will focus on less common inflammatory skin diseases.
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