Pekka Erkko

Cyclosporin in atopic dermatitis: time to relapse and effect of intermittent therapy

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe alopic dermatitis after a 6‐week treatment period with CyA at 5 mg/kg per day. After a follow‐up of 6‐26 weeks, depending on the time‐point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi‐weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re‐treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow‐up, the relapse rates were 71 and 90%. respectively. However, after the first treatment period five patients did not relapse during the 26‐week follow‐up period; the corresponding number was two after the second treatment period. The remission obtained in these seven patients was of clinical relevance, as their mean disease activity score at the end of the follow‐up periods was only 28% (range 11–40) and 43% (both patients), respectively, of their own baseline score. In contrast with the rapid relapse of the dermatitis in the other patients after CyA was stopped, all disease parameters showed improvement when these patients were seen 1 year after the study, i.e. the mean activity score was 17.8 (58% of baseline). All seven patients who did not relapse after the first or second treatment period were still in remission after 1 year, and their mean activity score was only 32% (range 10–69) of their own baseline score. The most common side‐effects were paraesthesiae and gastrointestinal discomfort. CyA dose was reduced in two patients because of drug‐related side‐effects; treatment was stopped prematurely in one patient. The present study confirms the efficacy of CyA in atopic dermatitis. It also suggests that CyA treatment may improve the long‐term outcome of atopic dermatitis, although most patients initially relapsed a few weeks after CyA was stopped.

Long-term follow-up of eczema patients treated with cyclosporine.

Cyclosporine is efficacious in short-term treatment of various eczematous disorders. In a follow-up study we have evaluated the long-term efficacy of cyclosporine in 75 patients, who in previous studies had been treated with cyclosporine for chronic actinic dermatitis (6 patients), atopic dermatitis (42 patients) and chronic hand eczema (27 patients), 4, 2 and 1 year after the initial treatment, respectively. Three out of 6 patients with chronic actinic dermatitis showed long-term efficacy. Two years after the initial treatment with cyclosporine (5 mg/kg/day for 1-2 treatment periods of 6 weeks) for atopic dermatitis the mean disease activity was significantly lower compared to baseline (58% decrease), and compared to the time of treatment stop no significant change had occurred. Of 37 evaluable patients 35 were still in remission. One year after the initial treatment with cyclosporine (3 mg/kg/day for 6 weeks) for chronic hand eczema the mean disease activity was significantly lower than at baseline (54% decrease), and compared to the time of treatment stop no significant change had occurred. Of 27 evaluable patients 21 patients were still in remission. The study suggests that long-term remissions are possible in eczematous diseases treated with cyclosporine, even for a relatively short treatment period. It must be stressed, however, that we did not have control groups for any of the studied patient groups.

Comparison of cyclosporin and UVAB phototherapy for intermittent one-year treatment of atopic dermatitis.

Although cyclosporin is effective for the treatment of severe atopic dermatitis, phototherapy is the standard second-line treatment for this disease. An open, randomized, controlled, parallel-group study was conducted to compare the efficacy, influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients. The main endpoints of the study were the number of days in remission and the influence on quality of life. Seventy-two patients were treated, 36 in each group. Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period. At the end of the study no difference between the 2 groups was noted in terms of quality of life. A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment. It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period.

Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%. showing high interpatient and intrapatient variability. The steady‐state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA‐SGC) and a newer oral formulation (sandimmun Neoral: CyA‐NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice‐daily treatment of CyA with a clinically effective dose of 2‐5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42‐day course of the study. At entry. patients were switched to CyA‐NOF for 4 weeks and then back to CyA‐SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady‐state on day 14 while the patients were on CyA‐NOF, and on day 42 while on CyA‐SGC. Switching from CYA‐SGC to CyA‐NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady‐state blood concentration‐time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in tthe clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA‐NoF: the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.

Cyclosporin for palmoplantar pustulosis

Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles, which is resistant to most treatments. Recently, two published uncontrolled studies suggested that cyclosporin (CsA) could be an effective treatment for PPP. Similarly, an unpublished, randomized, placebo-controlled study showed that CsA is effective in preventing new pustule formation in PPP. In the present paper we review the treatment of PPP with special emphasis on CsA treatment.