Reduction In Psoriasis Area And Severity Index Score Research Articles

Infliximab for the treatment of adults with psoriasis

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of infliximab for the treatment of moderate to severe plaque psoriasis, in accordance with the licensed indication, based on the evidence submission from Schering-Plough to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer's definition of the decision problem were severity [Psoriasis Area and Severity Index (PASI) score], remission rates, relapse rates and health-related quality of life. The main evidence in the submission comes from four randomised controlled trials (RCT) comparing infliximab with placebo and eight RCTs comparing either etanercept or efalizumab with placebo. At week 10, patients on infliximab had a significantly higher likelihood of attaining a reduction in PASI score than placebo patients. There were also statistically significant differences between infliximab and placebo in the secondary outcomes. In the comparator trials both the efalizumab and etanercept arms included a significantly higher proportion of patients who achieved a reduction in PASI score at week 12 than the placebo arms. No head-to-head studies were identified directly comparing infliximab with etanercept or efalizumab. The manufacturer carried out an indirect comparison, but the ERG had reservations about the comparison because of the lack of information presented and areas of uncertainty in relation to the included data. The economic model presented by the manufacturer was appropriate for the disease area and given the available data. The cost-effectiveness analysis estimates the mean length of time that an individual would respond to infliximab compared with continuous etanercept and the utility gains associated with this response. The base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with continuous etanercept for patients with severe psoriasis was 26,095 pounds per quality-adjusted life-year. A one-way sensitivity analysis, a scenario analysis and a probabilistic sensitivity analysis were undertaken by the ERG. The ICER is highly sensitive to assumptions about the costs and frequency of inpatient stays for non-responders of infliximab. The guidance issued by NICE in August 2007 as a result of the STA states that infliximab within its licensed indication is recommended for the treatment of adults with very severe plaque psoriasis, or with psoriasis that has failed to respond to standard systematic therapies. Infliximab treatment should be continued beyond 10 weeks in people whose psoriasis has shown an adequate response to treatment within 10 weeks. In addition, when using the Dermatology Life Quality Index (DLQI), care should be taken to take into account the patient's disabilities, to ensure DLQI continues to be an accurate measure.

Balneotherapy for chronic plaque psoriasis at Comano spa in Trentino, Italy

Thermal therapy is used worldwide in the treatment of psoriasis but few controlled studies have evaluated its efficacy and safety. We studied the efficacy and safety of balneotherapy compared to photobalneotherapy performed at Comano spa in Trentino, Italy, in chronic plaque psoriasis in a prospective, nonrandomized, open study. Three hundred adult patients with mild to severe chronic plaque psoriasis were assigned to either balneotherapy or photobalneotherapy with daily narrow-band ultraviolet B for a mean period of 1 or 2 weeks, reflecting the times that most patients can dedicate to thermal therapy. Patients were evaluated at baseline and end of treatment for psoriasis area and severity index (PASI) and body surface area; self-administered PASI (SAPASI) and Skindex-29 were evaluated at the same times, and also at 4 months by a mailed questionnaire. One-week balneotherapy or photobalneotherapy resulted in a significant reduction in PASI score (11.54% +/- 2.76 and 12.76% +/- 3.79, respectively; mean +/- standard deviation; p < 0.001). Two-week therapy induced a greater response with photobalneotherapy than with balneotherapy alone, with PASI reduction of 19.8% +/- 24.5 and 13.5% +/- 23.1 (p < 0.005), respectively. These results were confirmed by SAPASI and Skindex-29 evaluation. The therapy was well tolerated. Skin improvement was mostly lost after 4 months. Short-term balneotherapy and photobalneotherapy could thus be offered to patients willing to temporarily discontinue pharmacologic therapy or as adjuvant therapy.

A comparative study of different treatment frequencies of psoralen and ultraviolet A in psoriatic patients with darker skin types (randomized‐controlled study)

Photochemotherapy psoralen and ultraviolet A (PUVA) is a viable option for treatment of psoriasis. However, concerns about its side effects have raised the need to change current PUVA protocols. The aim of this study is to determine whether reducing the treatment frequency of PUVA to twice/week instead of three times/week would affect the efficacy of PUVA therapy. The study included 20 psoriatic patients, randomized into two groups, 10 patients in each group. The first group received two weekly sessions, the second group received three. The study lasted until complete clearance or for 12 weeks (endpoint). Psoriasis area and severity index (PASI) score was done prior to therapy, at mid therapy and at end of therapy (PASI final). No significant different in PASI final and in the percentage of reduction of PASI score between both groups (P value >0.05) was found. However, a significant difference in the total number of sessions and the total cumulative UVA doses between both groups was found (P value <0.001). Our study suggests reducing PUVA frequency and the cumulative UVA dose does not compromise the efficacy of PUVA, but it may improve its benefit/risk ratio. RESTRICTIONS: Few number of cases.

Efficacy of Etanercept in the Management of Plaque Psoriasis and Psoriatic Arthritis

Etanercept is a fully human dimeric fusion protein that reversibly binds tumor necrosis factor α. The first approved indication for etanercept was for the treatment of rheumatoid arthritis. It has also been shown to be highly efficacious in numerous large-scale trials for the treatment of plaque psoriasis; this indication was approved in Canada, the United States, and Europe. The recommended dosing of etanercept for plaque psoriasis is 50 mg twice weekly for 12 weeks, followed by a maintenance dose of 50 mg per week. Etanercept given at 50 mg twice weekly for 12 weeks significantly improved plaque psoriasis, as assessed by the Psoriasis Area and Severity Index (PASI), in which 75% reduction in PASI scores (PASI 75) has been the gold standard for judging effective therapy. Dosing given for 12 weeks produced PASI 75 rates of 47 to 49% in the phase 3 clinical trials. Longer treatment periods at this dosage have been investigated, from 24 to 48 weeks, with PASI 75 increasing to 63%. The importance of quality of life for psoriasis patients has been the focus of recent trials, and etanercept has been shown significant improvement in quality of life measures. Interim results from a phase 3b study suggest that etanercept may help reduce the burden of health care resources use by psoriatics. Etanercept has also shown efficacy in nail psoriasis. Case reports indicate that etanercept may be useful in psoriatic erythroderma, pustular psoriasis, guttate psoriasis, and palmopustular psoriasis. Etanercept is an effective biologic agent currently approved for the management of plaque psoriasis and psoriatic arthritis.

Adalimumab for long‐term treatment of psoriatic arthritis: Forty‐eight week data from the adalimumab effectiveness in psoriatic arthritis trial

To evaluate the efficacy and safety of treatment with adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, over 48 weeks in patients with moderate to severe psoriatic arthritis (PsA). Patients who completed the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), a 24-week, double-blind study of adalimumab versus placebo in PsA, could elect to receive open-label adalimumab, 40 mg subcutaneously every other week after week 24. Radiographs were obtained at week 48 and were read with radiographs obtained previously. Clinical and radiographic efficacy data were analyzed overall and in patient subsets. Safety data were collected over 48 weeks. At week 48, patients from the adalimumab arm of ADEPT (n = 151) had achieved American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 response rates of 56%, 44%, and 30%, respectively. Among those evaluated with the Psoriasis Area and Severity Index (PASI) (n = 69), PASI50, PASI75, PASI90, and PASI100 response rates (> or =50%, > or =75%, > or =90%, and 100% reduction in PASI scores, respectively) were 67%, 58%, 46%, and 33%, respectively (ACR and PASI response rates were analyzed using nonresponder imputation). Improvements in disability, as measured by the Disability Index of the Health Assessment Questionnaire (mean change in score -0.4) were sustained from week 24 to week 48. At week 24 and week 48, the mean changes from baseline in the modified total Sharp score were -0.1 and 0.1, respectively, for patients who received adalimumab for 48 weeks (n = 133), and 0.9 and 1.0, respectively, for patients who received placebo for 24 weeks followed by adalimumab for 24 weeks (n = 141). Adalimumab demonstrated clinical and radiographic efficacy regardless of whether patients were receiving methotrexate (MTX) at baseline. Adalimumab was generally safe and well tolerated through week 48. Adalimumab improved joint and skin manifestations, reduced disability, and inhibited radiographic progression over 48 weeks in patients with PsA who were participants in ADEPT. MTX use at baseline was not required for clinical or radiographic efficacy. Adalimumab had a good safety profile through week 48.

Treatment of palmoplantar psoriasis with monochromatic excimer light (308-nm) versus cream PUVA

Palmoplantar psoriasis is a chronic disease, which is very resistant to treatment and often leads to severe disabilities. Photochemotherapy employing psoralens combined with UVA irradiation (PUVA) is a well-accepted therapy for palmoplantar psoriasis. Its topical application (bath PUVA; cream PUVA) avoids the typical side effects of orally applied psoralens. We compared the efficacy of cream PUVA therapy with monochromatic excimer light therapy, a treatment modality employing 308-nm UVB radiation generated by a new kind of light source. Ten patients with psoriasis of the palms and soles were randomly assigned to receive cream PUVA on one side and 308-nm UVB on the contralateral side. Based on the psoriasis area and severity index (PASI) score, clinical assessment was carried out before and 5 weeks after the beginning of the study. At the end of the treatment period both test groups showed a remarkable PASI score reduction (308-nm UVB, 63.57%; cream PUVA, 64.64%). No relevant adverse effects were observed, except for mild irritation in a few patients. After a 12-week follow-up, a relapse of the disease was only observed in one patient. Thus, mono-chromatic excimer light cleared palmoplantar psoriasis as rapidly as cream PUVA. In contrast to cream PUVA, monochromatic excimer light therapy is not associated with prior drug application. This might lead to a lower incidence of adverse reactions and better compliance. Therefore, monochromatic excimer light therapy seems to be a useful new therapeutic option for palmoplantar psoriasis.

Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: Updated results from an ongoing trial

Efalizumab is a T cell-targeted therapy for psoriasis. We sought to evaluate the efficacy and safety of long-term, continuous efalizumab therapy. Of 339 patients enrolled in this ongoing, open-label, phase III study, after 3 months 290 qualified for and entered the maintenance treatment phase. Results for the first 27 months of this 36-month continuous therapy trial are available. At month 3, 41% of patients achieved at least a 75% reduction in Psoriasis Area and Severity Index (PASI) score; at month 27, 47% achieved at least a 75% reduction in PASI score (intent to treat, n = 339). Among patients eligible for maintenance therapy (n = 290), 56% achieved at least a 75% reduction in PASI score at month 27. Moreover, the at least 90% reduction in PASI score rate increased through 18 months (33%). The safety profile with efalizumab was sustained throughout 27 months of continuous treatment with no new common events over time. Because the extended treatment period was not a randomized clinical trial, no formal comparative analyses versus placebo were conducted. Three-month placebo data from randomized, parallel, placebo-controlled studies are briefly discussed. These results suggest that efalizumab maintains, and in some patients continues to improve, efficacy during long-term therapy.

Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis

Efalizumab targets T cell-mediated steps important in psoriasis immunopathogenesis. We sought to evaluate the efficacy and safety of efalizumab retreatment in patients with moderate to severe plaque psoriasis. In this open-label, phase III study, 365 patients who received efalizumab therapy during an earlier clinical trial were retreated with 12 weeks of subcutaneous efalizumab (1 mg/kg/wk) 35 days or more after their last dose of efalizumab. After 12 weeks of efalizumab retreatment, 56.9% of patients achieved 50% or more improvement from baseline Psoriasis Area and Severity Index (PASI) and 25.3% achieved at least 75% reduction in PASI score. The mean percentage PASI improvement from baseline was 51.2%. Overall, 76.1% of patients surveyed were "very satisfied" or "satisfied" with the efficacy of efalizumab. The safety profile of efalizumab retreatment was similar to that observed in patients receiving efalizumab for the first time. Not all patients received sufficient exposure to efalizumab during their previous efalizumab clinical trial to allow for determination of their initial response to efalizumab. Of 365 patients enrolled in the study, 282 received at least 12 weeks of prior efalizumab therapy; of these patients, 208 (73.8%) achieved a PASI-50 response from their previous therapy. These results suggest that retreatment with efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.

Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6)

Disordered differentiation and hyperproliferation of keratinocytes with inflammation are the hallmarks of psoriasis. Ligand activation of peroxisome proliferator receptor-gamma (a class of nuclear receptors) by thiazolidinediones can normalize the histologic features of psoriasis. In a 10-week, double-blind, randomized, placebo-controlled, parallel-group study, 70 patients with moderate to severe psoriasis received one of the following treatments: pioglitazone 15 mg, pioglitazone 30 mg or placebo. Efficacy was evaluated by observing the change in the psoriasis area and severity index (PASI) after 10 weeks of treatment. There was a dose-dependent improvement in psoriasis. Median PASI scores at the end of 10 weeks were significantly reduced in the pioglitazone treatment groups as compared to the placebo-treated group. The psoriasis lesions cleared in more than 40% of patients treated with pioglitazone as compared to 12.5% of those with placebo. The percentage reduction in mean PASI scores was 21.6%, 41.1% and 47.5% in the placebo, pioglitazone 15 mg, and 30 mg groups, respectively. No serious adverse events were detected. This is the first report from a controlled trial demonstrating that pioglitazone could be considered as an efficacious and safe agent for the treatment of plaque psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined.

A combination therapy of calcipotriol cream and PUVA reduces the UVA dose and improves the response of psoriasis vulgaris

BACKGROUND: The addition of calcipotriol ointment to PUVA therapy for psoriasis vulgaris results in a lower total UVA dose and a faster onset of response. The addition of calcipotriol cream to PUVA, however, has not been studied.OBJECTIVE: To investigate whether combining calcipotriol cream with PUVA therapy has a UVA sparing effect.METHODS: We performed a randomized, multicentre, vehicle‐controlled, double‐blind, 12‐week comparative study including 120 patients with psoriasis covering 20–50% body surface area. The study consisted of a washout phase followed by a 10‐week treatment phase. PUVA therapy three times weekly was added within 1 week after randomization. Efficacy was assessed by the Psoriasis Area and Severity Index (PASI).RESULTS: At baseline the mean PASI scores were 17.5 and 19.2 in the calcipotriol and vehicle (placebo) groups, respectively. At the end of treatment, the mean PASI scores were 2.65 and 7.03 (p<0.01), respectively. A reduction in PASI score >90% was observed in 69% of the patients in the calcipotriol‐treated group and in 36.4% of the patients in the vehicle group (p<0.01).CONCLUSION: Calcipotriol cream plus PUVA clearly reduces the cumulative dose of UVA and improves the response of psoriasis vulgaris to PUVA.

Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial

Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 microg g(-1). The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0.01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3.6 (95% confidence interval 1.0-6.2, P = 0.008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0.05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0.8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0.02) at 16 204 mJ cm-2 compared with 21 082 mJ cm-2 for the control group. We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.

Dead sea bath salt for the treatment of psoriasis vulgaris: a double‐blind controlled study

AbstractBack‐ground The beneficial effect of the Dead Sea (DS) area in psoriasis is attributed in part to the DS water, which has a high content of minerals,Aim The aim of the study was 10 evaluate the sole therapeutic effect of DS salt in psoriasis.Patients and Methods Thirty patients wild psoriasis vulgaris, involving &gt;15% body area, were included in the study, which was conducted in a double‐blind controlled manner. Treatment consisted of once daily baths, heated lo 35°C, of 20 min duration, for 3 weeks, of cither DS bath salt (group I) or common salt (group II). Clinical evaluation was based on Psoriasis Area and Severity Index (PASI) score determination before and after treatmentResults Twenty‐five patients 113 in group 1 and I 2 in group II) terminated the treatment protocol. In both groups, treated by US hath salt and common salt, respectively, the mean PASI score before treatment (18.6, ± 9.4 and 15.7 ± 7.1. respectively) decreased significantly al the end of the treatment (11.4 ± 6.1 and 11.4± 6.6, respectively). The mean percentage reduction of PASI score at the end of the treatment regimen, was higher in patients treated with IDS bath salt (34.8%) compared to patients treated with common salt (27.5%) (P &gt; 0.05). The mean percentage reduction a month after termination of the treatment protocol was higher in patients treated with DS hath salt (43.6%) than in those treated with common salt (24%) (P &gt; 0.05).Conclusions The present study implies a beneficial effect to bathing wish either DS hath salt or common salt as a sole therapy for psoriasis vulgaris. However, we observed an enhanced beneficial effect of DS hath salt compared to common salt.

Dead sea bath salt for the treatment of psoriasis vulgaris: a double-blind controlled study

Background The beneficial effect of the Dead Sea (DS) area in psoriasis is attributed in part to the DS water, which has a high content of minerals.Aim The aim of the study was to evaluate the sole therapeutic effect of DS salt in psoriasis.Patients and Methods Thirty patients with psoriasis vulgaris, involving >15% body area, were included in the study, which was conducted in a double-blind controlled manner. Treatment consisted of once daily baths, heated to 35°C, of 20 min duration, for 3 weeks, of either DS bath salt (group I) or common salt (group II). Clinical evaluation was based on Psoriasis Area and Severity Index (PASI) score determination before and after treatment.Results Twenty-five patients (13 in group I and 12 in group II) terminated the treatment protocol. In both groups, treated by DS bath salt and common salt, respectively, the mean PASI score before treatment (18.6±9.4 and 15.7±7.1, respectively) decreased significantly at the end of the treatment (11.4±6.1 and 11.4±6.6, respectively). The mean percentage reduction of PASI score at the end of the treatment regimen, was higher in patients treated with DS bath salt (34.8%) compared to patients treated with common salt (27.5%) (P>0.05). The mean percentage reduction a month after termination of the treatment protocol was higher in patients treated with DS bath salt (43.6%) than in those treated with common salt (24%) (P>0.05).Conclusions The present study implies a beneficial effect to bathing with either DS bath salt or common salt as a sole therapy for psoriasis vulgaris. However, we observed an enhanced beneficial effect of DS bath salt compared to common salt.

Efficacy of low-dose cyclosporin A in psoriasis: results of dose-finding studies

The efficacy of cyclosporin A (CyA) in severe psoriasis was analysed in 457 adult patients included in five European multicentre dose-finding studies. Initial CyA doses were 1.25 mg/kg/day in 33 patients, 2.5-3 mg/kg/day in 285 and 5 mg/kg/day in 139. After 3 months of treatment, the reduction of the Psoriasis Area and Severity Index (PASI) score was 35 +/- 6% with 1.25 mg/kg/day of CyA, 57 +/- 2% with 2.5 mg or 3 mg/kg/day and 86 +/- 2% with 5 mg/kg/day (P less than 0.001). The rates of success, defined by a PASI score reduction greater than or equal to 75% or a score less than or equal to 8, were 24%, 52% and 88%, respectively. There were no differences in age, initial severity or duration of psoriasis. The improvement was maintained for 9 months or more in the majority of patients receiving continuous CyA therapy.

(8) Comparison of psoriasis treated with cyclosporin alone or cyclosporin and clobetasol propionate

Cyclosporin A (CyA) in the low dosage of 3 mg/kg/day has been shown to clear psoriasis; however, the disease relapses soon after withdrawal of the drug. Immunological studies have demonstrated persistence of activated T helper (TH) cells within the epidermis after clearance of psoriatic plaques with cyclosporin but disappearance if clearance is achieved by the use of topical clobetasol propionate (CP). If the relapse is a result of resumption of function by epidermal-activated TH cells then combination therapy with CP and CyA should delay the rate of relapse. Six patients with chronic plaque psoriasis were treated with CyA at a dose of 3 mg/kg/day for a period of 6 weeks; during the first 2 weeks CP was applied twice daily to the psoriatic plaques. A second group of six psoriatic patients was treated with cyclosporin alone. The psoriasis was scored at weekly intervals during treatment using the Psoriasis Area and Severity Index (PASI), and for 4 weeks after cessation of treatment. Using CyA alone, the mean time taken to achieve 80% reduction in PASI score was 7·3 ± 2·4 weeks compared to 4·2 ± 2·1 weeks with CyA and CP (P < 0·05). Four weeks after withdrawal of treatment the average percentage deterioration in PASI score was 29·2 in the CyA group and 17·8 in the CyA + CP group. This difference was not significant. Thus, the addition of CP to CyA in the management of psoriasis cleared psoriasis faster than CyA alone but did not slow the relapse rate. It would seem that the initiating factor responsible for attracting TH cells into the epidermis is not cleared by either treatment.