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Severe combined immunodeficiency mouse-human skin chimeras: a unique animal model for the study of psoriasis and cutaneous inflammation.

Elucidation of the molecular and cellular mechanisms responsible for the pathogenesis of psoriasis had been significantly handicapped due to lack of an ideal animal model. To overcome this hurdle several investigators have developed a number of animal models for psoriasis. Recent establishment of the SCID-human skin chimeras with transplanted psoriasis plaques has opened new vistas to study the molecular complexities involved in psoriasis. This model also offers a unique opportunity to investigate various key biological events such as cell proliferation, angiogenesis, homing in of T cells in target tissues, neurogenic inflammation and cytokine/chemokine cascades involved in an inflammatory reaction. The SCID mouse model will be of immense help to target the cellular and molecular events associated with these pathogenic processes and develop novel drugs for psoriasis and other inflammatory diseases. In this article we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

Animals↗

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis.

BACKGROUND: T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system. OBJECTIVES: To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients. METHODS: ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study. RESULTS: All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia. CONCLUSIONS: ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.

Adenosine Deaminase↗

Novel immune-based therapies for psoriasis.

The primacy of the immune system in the pathogenesis of psoriasis is a well-established concept to the extent that psoriasis has been classified as a T-cell-mediated, autoimmune disease. An explosion of knowledge concerning immunological events in psoriasis and the clinical efficacy of immunologically directed therapies, such as cyclosporin, support this concept. Armed with this understanding and modern biotechnology, novel interventions have been developed to treat psoriasis. The aim of these therapies is to provide selective, immunologically directed intervention with the hope that such specificity will result in fewer side-effects than traditional therapies. Of interest and importance, these pharmaceutical interventions also act as a form of investigational tool in psoriasis. Their relative efficacy in the psoriatic process provides useful insights into the hierarchial importance of immune events in the disease process and recent evidence suggests that innate rather than acquired immunity has a key role. This article reviews recent developments in immune-based therapies for psoriasis.

Cytokines↗

Cyclosporin trough levels: is monitoring necessary during short-term treatment in psoriasis? A systematic review and clinical data on trough levels.

BACKGROUND: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin. METHODS: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated. RESULTS: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.

Adult↗

Response of psoriasis to sunbed treatment: comparison of conventional ultraviolet A lamps with new higher ultraviolet B-emitting lamps.

BACKGROUND: Sunbeds fitted with conventional ultraviolet (UV) A lamps that have about 0.7% UVB emission are widely used by patients with psoriasis even though they are minimally effective. A new fluorescent sunbed lamp has been developed that emits a higher proportion of UVB (4.6%) than conventional lamps and also requires shorter exposure times to achieve equivalent erythema. OBJECTIVES: To perform a randomized, within-patient comparison of conventional sunbed lamps (Cleo Performance) with the new lamps (Cleo Natural) in the treatment of psoriasis. METHODS: A sunbed and canopy unit were modified to allow exposure to Cleo Performance lamps on one side of the body (front and back) and Cleo Natural lamps to the other side of the body. Two studies were done. In study 1, equal erythemal doses were given from the two lamp types. In study 2, equal exposure times were given. We treated 34 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. RESULTS: Fourteen patients completed each study. In study 1, there was no significant difference in median improvement in half-body PASI score for the two lamp types. In study 2, there was a significant difference in PASI score improvement between the two lamps (median Cleo Performance change minus median Cleo Natural change was - 2.20; 95% confidence interval - 3.75 to - 0.65; P = 0.006). CONCLUSIONS: That no difference in response was found when equal erythemal doses were given suggests that the spectral emission of the Cleo Natural lamp is of no greater advantage for clearance of psoriasis than conventional lamps. However, the Cleo Natural lamps are more erythemally powerful, and exposure times similar to those used in conventional sunbeds result in a significant improvement of psoriasis. The risk of non-melanoma skin cancer from different patterns of exposure to Cleo Natural lamps can be estimated using established numerical models.

Adolescent↗

Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis.

BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.

Administration, Topical↗

Salient features and HLA markers of childhood psoriasis in Kuwait.

A total of 305 consecutive Kuwaiti children with psoriasis were studied for clinical features and 50 children were tissue typed for HLA class I and class II antigens. The salient features of psoriasis in these children included: female preponderance (M : F ratio, 1:1.5); peak age of onset between 2 and 8 years; scalp as the most common site of onset (30%); scalp and extensors of legs as commonly affected sites (52.5% each); plaque psoriasis the most common clinical type (89%); and a positive family history of psoriasis in 34% of the patients. Kuwaiti children with psoriasis showed a significant association with HLA-A3, Cw1, and DR7 antigens and those with a positive family history of psoriasis had a significant association with HLA-DR8 antigen.

Biomarkers↗

Group therapy: a useful and supportive treatment for psoriasis patients.

BACKGROUND: Because of the social and psychologic effects of psoriasis, many patients with the disease experience considerable emotional stress which in tum can aggravate the disease. This study was undertaken to determine the usefulness of group therapy in helping psoriasis patients cope with their condition. METHODS: A structured program consisting of seven sessions was carried out with 10 psoriasis patients under the guidance of a social worker. The program covered knowledge of psoriasis, feelings of acceptance, stress management, and coping with daily living. An evaluation was carried out at the end of the program. RESULTS: Most patients found that the program enhanced their knowledge of psoriasis and helped them to cope better, and that they also learned from each other how to handle stress and gained self-confidence. CONCLUSION: Group therapy is a useful adjuvant therapy for psoriasis patients in coping with their illness.

Adult↗

A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.

BACKGROUND: Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis. AIM: To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp. METHODS: Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events. RESULTS: After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events. CONCLUSIONS: Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.

Administration, Topical↗

Frequent use of tobacco and alcohol in Chinese psoriasis patients.

BACKGROUND: This study aimed to explore smoking and drinking as risk factors in psoriasis. METHODS: Data collected from 789 psoriasis patients and 789 healthy controls were analyzed to determine whether there was an association between smoking/drinking and psoriasis. RESULTS: The proportion of male psoriasis patients using tobacco and alcohol was much higher than that of the control group (P < 10(-6)), whereas no statistical differences were found between female smokers and the control group. In general, heavy smokers were more likely to have severe psoriasis. CONCLUSION: Tobacco use in patients is correlated with psoriasis.

Adolescent↗

Clinical response to alefacept: results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis.

BACKGROUND: There is a current lack of safe and effective psoriasis therapies that provide patients with lasting remissions after treatment is discontinued. Alefacept, a novel and selective biological agent, has demonstrated durable efficacy in patients with chronic plaque psoriasis, and its efficacy has been correlated with reductions in memory-effector T cells. OBJECTIVE: To demonstrate the efficacy and safety of both one and two 12-week courses of alefacept 7.5 mg given once weekly as an intravenous (IV) bolus injection in patients with chronic plaque psoriasis. METHODS: Multicentre (51 centres in the USA and Canada), randomized, double-blind, parallel-group study comparing once-weekly alefacept 7.5 mg IV or placebo for two 12-week treatment courses. Each course had a 12-week follow-up phase. Patients were eligible for enrollment if they were > or =16 years of age, had chronic plaque psoriasis for > or =12 months involving > or =10% body surface area, and had CD4+ T-cell counts at or above the lower limit of normal. RESULTS: 553 patients received treatment in Course 1, and 449 were treated in Course 2. The cohorts were well balanced for demographic and baseline disease characteristics. During the treatment and follow-up period of Course 1, 28% of patients treated with alefacept achieved > or =75% reduction in Psoriasis Area and Severity Index (PASI), compared with 8% of placebo-treated patients (P < 0.001). Patients achieving > or =75% reduction in PASI following a single 12-week course of alefacept maintained > or =50% reduction in PASI for a median of over 7 months. Among patients who received a second course of alefacept therapy, 71% achieved > or =50% reduction in PASI, and 40% achieved > or =75% reduction in PASI over two treatment courses. One or two 12-week courses of alefacept were similarly well tolerated. CONCLUSIONS: Treatment with alefacept 7.5 mg IV provided highly significant improvements in all measures of psoriasis disease activity compared with placebo. A second course of alefacept provided additional benefit.

Adolescent↗

The role of oxidants and antioxidants in psoriasis.

BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated erythema and scaly plaques. The pathogenesis of psoriasis still remains unclear. An increased reactive oxygen species (ROS) and insufficient antioxidant activity have been determined in psoriatic lesions. AIM OF THE STUDY: To evaluate and compare superoxide dismutase (SOD) and glutathione peroxidase (GP) activity in erythrocytes, catalase (CAT) activityand malondialdehyde (MDA) levels in serum of subjects with psoriasis and controls as well as MDA levels in skin biopsies from both groups. STUDY POPULATION: Twenty-two psoriatic patients (12 women and ten men) and 22 (12 women and ten men) healthy controls were involved in this study. FINDINGS: Statistically significant decreased levels of erythrocyte SOD and GP activities were noted in psoriatic subjects. Furthermore, a statistically significant increased serum CAT activity was found in the psoriasis group. No statistically significant difference was found in the serum MDA levels in the two groups, however, statistically significant increased tissue levels of MDA were noted in the psoriasis group. CONCLUSIONS: Our results support the hypothesis of an imbalance in the oxidant-antioxidant system in psoriasis.

Adult↗

Interleukin-10 promoter polymorphism in psoriasis.

Beneficial effects of interleukin-10 therapy and lower endogenous interleukin-10 formation compared with atopic dermatitis and cutaneous T cell lymphomas indicated that interleukin-10 is a key cytokine in psoriasis. The interleukin-10 promoter is highly polymorphic, with two informative microsatellites, interleukin-10.G and interleukin-10.R. In order to understand whether interleukin-10 itself is a predisposing gene for the psoriasis susceptibility we analyzed interleukin-10 promotor polymorphism in patients. The distribution of interleukin-10.G and interleukin10.R microsatellite alleles did not vary between patients (n = 78) and healthy controls (n = 80). In addition, when the psoriasis patients were stratified according to age of onset (younger than 40 y of age, or age 40 and older), no difference in allele distribution was observed; however, a clear differential distribution was revealed at the interleukin10.G locus when patients were stratified according to whether they had a positive family history of psoriasis (p = 0.04). This difference was due to an over-representation of the interleukin10.G13 allele in those patients with familial disease (40.4% vs 19.6%, Chi-square = 7.292, p = 0.007). The positive association of allele interleukin10.G13 with familial psoriasis was especially true when patients with an early onset (< 40 y of age) of the disease were compared with those patients with early onset against a nonfamilial background (39.6% vs 14.5%, Chi-square = 8.959, p = 0.003). Patients with age-of-onset of less than 40 were 4-fold [odds ratio = 3.85 (1.55--9.62)] more likely to have a psoriatic family background if they carried this interleukin10.G13 allele. These data suggest that the interleukin-10 locus contributes to the heritability of psoriasis susceptibility.

Alleles↗

Identification of a commonly used CDR3 region of infiltrating T cells expressing Vbeta13 and Vbeta15 derived from psoriasis patients.

Psoriasis is a common inflammatory skin disease that is thought to be mediated by activated T cells. In this study, the complementarity-determining region 3 (CDR3) in T cell receptors was examined for a common sequence motif among the T cells infiltrated in psoriatic lesional skin. A common specific CDR3 motif (Vbeta13-DWTSGV-Jbeta2.7) in lesions from psoriasis patients was identified by polymerase-chain-reaction-based spectratyping analysis and DNA sequencing. In addition, VDJ rearrangement with highly homologous amino acid composition in the CDR3 was observed in Vbeta15 of T cell receptors in lesions derived from psoriatic patients. Remarkably, T cell receptors containing the Vbeta13-DWTSGV-Jbeta2.7 were also found in the clinically normal skin from the psoriasis patients, which might seem to be responsible for the artificial production of psoriatic lesions. The identified CDR3 motif was highly expressed in cutaneous lymphocyte antigen (CLA+) cells of peripheral blood mononuclear cells from psoriasis patients compared with the expression in healthy individuals. This result showed that the infiltrated CLA+ T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in peripheral blood mononuclear cells from psoriasis patients might be involved in the development of psoriatic lesions. In addition, the results in this study suggest that the infiltrated T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in psoriatic lesions may be involved in the pathogenesis of psoriasis.

Amino Acid Motifs↗

Association of TAP and HLA-DM genes with psoriasis in Koreans.

To investigate the possible involvement of antigen-processing genes in the pathogenesis of psoriasis, we analyzed the polymorphisms of the TAP1, TAP2, LMP2, LMP7, DMA, and DMB genes in 98 Korean psoriasis patients and compared them with 184 healthy controls. The frequencies of TAP2*B/B [relative risk (RR)=3.6, p<0.0002] and TAP2*B (RR=1.7, p<0.05) were significantly increased, but TAP1*B (RR=0.3, p<0.002) and TAP2*A (RR=0.6, p<0.03) were significantly decreased, in the patients compared to the controls. We performed further analysis on the TAP1 and TAP2 single nucleotide polymorphisms and found significant differences between the patients and controls in TAP1 single nucleotide polymorphism at position 637 and in TAP2 at 665. In HLA-DM, DMA*0102 (RR=2.5, p<0.0003) was significantly increased, but DMA*0101/0101 (RR=0.4, p<0.0004) and DMB*0103/0103 (RR= 0.3, p<0.005) were significantly decreased in the patients compared to the controls. The TAP and HLA-DM alleles were also analyzed according to the age of onset of psoriasis in the patients (types I and II). It was found that the HLA-DM alleles showed a greater association in type I than type II patients. An analysis of the linkage disequilibrium and stratification also indicated that the alleles of TAP and HLA-DM might be independently associated with HLA-Cw*0602 in psoriasis patients. The stratification analysis between DMA*0101/0101 and DMB*0103/0103 showed that a certain factor, controlled by a gene located between DMA and DMB, might provide strong protection against psoriasis, independently of Cw*0602, in our Korean population. In conclusion, our data suggest that the TAP and HLA-DM alleles could lead to genetic susceptibility toward psoriasis in Koreans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A pilot study to assess the safety and efficacy of topical calcipotriol treatment in childhood psoriasis.

Childhood psoriasis is more extensive and severe compared with that of adults. Therefore an effective and safe treatment modality is needed. Although a few studies of childhood psoriasis indicate that treatment with calcipotriol is safe and effective, short-term studies cannot reflect the exact effect of calcipotriol on systemic calcium homeostasis. Our purpose was to study the long-term efficacy and safety of calcipotriol for childhood psoriasis. An uncontrolled pilot study, with long-term follow-up for as long as 106 weeks, using open-label calcipotriol ointment was conducted in 12 psoriasis patients less than 15 years of age. Response to treatment was assessed by the psoriasis area and severity index (PASI) and serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, as well as routine laboratory analyses including serum calcium and phosphate, which were measured before and after the course of treatment. At the end of the study, the patients showed significant improvement in PASI scores compared with the baseline level. No serious side effects, including those related to calcium homeostasis, were detected. The mean values of 1,25-dihydroxyvitamin D3, however, were decreased and half of the patients had levels below the normal range. In conclusion, it is thought that calcipotriol ointment is an effective treatment modality for long-term use in childhood psoriasis. However, although not lowering serum calcium and phosphate levels, the long-term use of calcipotriol in childhood may possibly decrease the serum values of endogenous vitamin D. Therefore monitoring of vitamin D metabolites may be necessary during calcipotriol therapy. More investigative studies are needed to resolve this issue.

Administration, Cutaneous↗

Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial.

BACKGROUND: Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects. METHODS: In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding. RESULTS: The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin. CONCLUSIONS: Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.

Administration, Oral↗

Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis.

BACKGROUND: Methotrexate and cyclosporine are well-known systemic therapies for moderate-to-severe chronic plaque psoriasis. We conducted a randomized, controlled trial comparing methotrexate and cyclosporine in terms of effectiveness, side effects, and the quality of life. METHODS: A total of 88 patients with moderate-to-severe psoriasis were randomly assigned to treatment for 16 weeks with either methotrexate (44 patients; initial dose, 15 mg per week) or cyclosporine (44 patients; initial dose, 3 mg per kilogram of body weight per day) and were followed for another 36 weeks. The primary outcome was the difference between groups in the psoriasis area-and-severity index after 16 weeks of treatment, after adjustment for base-line values; scores were determined in a blinded fashion by trained observers. RESULTS: Two patients were excluded from the analysis after randomization because they were found to be ineligible, and one patient withdrew his consent. Twelve patients in the methotrexate group had to discontinue treatment because of reversible elevations in liver-enzyme levels, and 1 patient in the cyclosporine group had to do so because of an elevation in the bilirubin level, but all 13 were included in the analysis. After 16 weeks of treatment, the mean (+/-SE) score for the psoriasis area-and-severity index decreased from 13.4+/-3.6 at base line to 5.0+/-0.7 among 43 patients treated with methotrexate, whereas the score decreased from 14.0+/-6.6 to 3.8+/-0.5 among 42 patients treated with cyclosporine. After adjustment for base-line values, the mean absolute difference in values at 16 weeks was 1.3 (95 percent confidence interval, -0.2 to 2.8; P=0.09). The physician's global assessment of the extent of psoriasis, the time to and the rates of remission, and the quality of life were similar in the two groups. CONCLUSIONS: No significant differences in efficacy were found between methotrexate and cyclosporine for the treatment of moderate-to-severe psoriasis.

Adult↗