Reduction In Psoriasis Area And Severity Index Score Research Articles

OP0076 Effect of Exercise and Dietary Weight Loss on Symptoms and Systemic Inflammation in Obese Adults with Psoriatic Arthritis: Randomized Controlled Trial

BackgroundPsoriatic arthritis (PsA) patients have a higher prevalence of comorbidities including obesity, metabolic syndrome, depression and premature cardiovascular disease. There is evidence that obesity is associated with PsA. Obesity leads...

Diet and physical exercise in psoriasis: a randomized controlled trial

Increased body mass index and weight gain are risk factors for psoriasis, and the prevalence of obesity in patients with psoriasis is higher than in the general population. Limited data exist regarding the role of diet in psoriasis. To assess the impact of a dietary intervention combined with physical exercise for weight loss on improving psoriasis in overweight or obese patients. This study included 303 overweight or obese patients with moderate-to-severe chronic plaque psoriasis who did not achieve clearance after 4 weeks of continuous systemic treatment. They were randomized to receive either a 20-week quantitative and qualitative dietary plan associated with physical exercise for weight loss or simple informative counselling at baseline about the utility of weight loss for clinical control of psoriatic disease. The main outcome was any reduction of the Psoriasis Area and Severity Index (PASI) from baseline to week 20. Intention-to-treat analysis showed a median PASI reduction of 48% (95% confidence interval 33.3-58.3%) in the dietary intervention arm and 25.5% (95% confidence interval 18.2-33.3%) in the information-only arm (P = 0.02). Among secondary outcomes, PASI score reduction of ≥ 50% significantly differed between study arms (49.7% with dietary intervention vs. 34.2% with information only, P = 0.006). The weight-loss target (a ≥ 5% reduction from baseline) was reached by 29.8% of patients in the dietary intervention arm compared with 14.5% in the information-only arm (P = 0.001). A 20-week dietetic intervention associated with increased physical exercise reduced psoriasis severity in systemically treated overweight or obese patients with active psoriasis.

The effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis: a prospective comparison of regular day care and day care with telemedicine

Evidence on the effectiveness and safety of short-contact dithranol therapy in paediatric psoriasis is sparse and based only on retrospective data. The best results are achieved in a time-consuming day-care setting. To study prospectively the effectiveness and safety of short-contact dithranol therapy in paediatric psoriasis. In addition, the effectiveness, safety, duration of treatment and number of visits between regular day care and day care with telemedicine were compared. Data were collected from the prospective observational Child-CAPTURE registry of children with psoriasis. Effectiveness was measured as the mean percentage improvement in Psoriasis Area and Severity Index (PASI). Safety was assessed by recording adverse events. The number of visits and duration of treatment were reported. For all patients a mean percentage reduction in PASI score of -69·3% was found, with no significant differences between regular day care and day care with telemedicine. The only adverse event reported was irritation of the skin. Neither the frequency of irritation during treatment nor the mean duration of treatment significantly differed between the two groups. Patients with telemedicine had significantly fewer visits. This first prospective observational study demonstrates that short-contact dithranol therapy in paediatric psoriasis is effective and safe. Regular day care and day care with telemedicine are equally effective. Telemedicine can be of additional value as it is less time consuming. We hope it will therefore make dithranol treatment appropriate for a larger number of children with psoriasis.

Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis.

The most commonly used types of phototherapy for treating psoriasis are narrow-band ultraviolet B (NB-UVB); broad-band ultraviolet B (BB-UVB), which includes selective (delivering radiation with a wavelength range of 305 to 325 nm) and conventional BB-UVB (280 to 320 nm); and psoralen ultraviolet A photochemotherapy (oral or bath PUVA). There is substantial controversy regarding their efficacy when compared with each other. To assess the effects of narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen ultraviolet A photochemotherapy for psoriasis. We searched the following databases up to August 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 7), MEDLINE (from 1946), and EMBASE (from 1974). We searched the following databases up to November 2012: CNKI (from 1974) and CBM (from 1978). We also searched trials registers and the OpenGrey database. We included all randomised controlled trials (RCTs) that compared NB-UVB phototherapy with BB-UVB or PUVA for treating psoriasis, which included chronic plaque psoriasis (CPP), guttate psoriasis (GP), and palmoplantar psoriasis (PPP). Two review authors independently conducted the study selection, 'Risk of bias' assessment, and data extraction. We included 13 RCTs, with a total of 662 participants. We report the results of intention-to-treat analyses (ITT) here. Our primary outcomes of interest were as follows: Participant-rated global improvement, Percentage of participants reaching Psoriasis Area and Severity Index (PASI) 75 (which meant equal to or more than 75% reduction in PASI score), Withdrawal due to side-effects, and Clearance rate.In one RCT of NB-UVB compared with oral PUVA in participants with CPP, the difference in PASI 75 was not statistically significant (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.63 to 1.32; N = 51; low quality). In three other RCTs of CPP, the clearance rates were inconsistent because in one, there was no difference between the groups (RR 1.01, 95% CI 0.91 to 1.12; N = 54), and in the other two, the clearance rates were statistically significantly in favour of oral PUVA: RR 0.66, 95% CI 0.47 to 0.93; N = 93 and RR 0.75, 95% CI 0.59 to 0.96; N = 100, respectively. Pooled data from these three studies indicated that withdrawals due to adverse events were not significantly different between either group (RR 0.71, 95% CI 0.20 to 2.54; N = 247; low quality).The evidence from the comparison of NB-UVB with bath PUVA in terms of clearance rate for CPP was also inconsistent: Pooled data from two left-right body comparison RCTs found no significant difference between the NB-UVB and bath PUVA groups (RR 1.79, 95% CI 0.46 to 6.91; N = 92; low quality), while a parallel RCT favoured bath PUVA (RR 0.18, 95% CI 0.05 to 0.71; N = 36; low quality).In participants with PPP, one RCT found there were no significant differences between NB-UVB treated sides and topical PUVA treated sides in terms of clearance rate (RR 0.09, 95% CI 0.01 to 1.56; N = 50; low quality).Two RCTs found NB-UVB plus retinoid (re-NB-UVB) and PUVA plus retinoid (re-PUVA) had similar effects for treating people with CPP or GP in terms of clearance rate (RR 0.93, 95% CI 0.79 to 1.10; N = 90; low quality).One RCT in people with CPP found no significant differences between NB-UVB and selective BB-UVB in terms of clearance rate (RR 1.40, 95% CI 0.92 to 2.13; N = 100; low quality) and withdrawals due to adverse events (RR 3.00, 95% CI 0.32 to 27.87; N = 100; low quality).No studies reported our primary outcomes for NB-UVB compared with conventional BB-UVB. Current evidence is very heterogeneous and needs to be interpreted with caution. The clearance rate between oral PUVA and NB-UVB is inconsistent among the included studies. Evidence regarding NB-UVB versus bath PUVA is also inconsistent. Re-NB-UVB and re-PUVA are similarly effective for treating people with CPP or GP. In practice, NB-UVB may be more convenient to use since exogenous photosensitiser is not required before phototherapy.NB-UVB is considered ineffective for PPP in clinical practice, and a small RCT did not detect a statistically significant difference between NB-UVB and topical PUVA for clearing PPP. NB-UVB seemed to be similar to selective BB-UVB for clearing CPP.Larger prospective studies are needed to confirm the long-term safety of NB-UVB.

Clinical efficacy of etanercept for the treatment of psoriasis

Objective To evaluate the efficacy profile of etanercept,a recombinant human type Ⅱ tumor necrosis factor receptor-Fc fusion protein,in patients with moderate to severe psoriasis.Methods A retrospective study was performed.This study included 24 patients with moderate to severe psoriasis vulgaris resistant to conventional therapy.They were treated with subcutaneous injection of etanercept 25 mg twice weekly for three months during February 2008 and August 2011.Six months of follow up was carried out.Clinical efficacy was evaluated by psoriasis area and severity index (PASI) and physician global assessment (PGA).Results After 24-week treatment,12 (50％) patients achieved a 75％ reduction in PASI score,1 (4.2％) patient failed to respond.Adverse reaction,such as erythematous swelling at the injection site,was observed in 4 patients.Conclusion Anti-tumor necrosis factor may be effective for the treatment of moderate to severe psoriasis recalcitrant to traditional therapy.

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone, narrowband ultraviolet B phototherapy alone, combination of calcipotriol and narrowband ultraviolet B phototherapy once a week, and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB-UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB-UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB-UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self-administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self-PASI scores among the four regimens. Although the serum levels of interleukin (IL)-17, IL-20 and IL-22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB-UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.

Effect of Narrow Band Ultraviolet B Therapy versus Methotrexate on Serum Levels of Interleukin-17 and Interleukin-23 in Egyptian Patients with Severe Psoriasis

Background. There is raised interest in the involvement of interleukin-(IL-)23/T-helper 17 cells (Th17) axis in the pathogenesis of psoriasis. Objectives. To compare the effect of narrow band ultraviolet B (NB-UVB) and methotrexate (MTX) therapy on serum levels of IL-17 and IL-23 in psoriatic patients. Methods. Thirty patients with severe plaque psoriasis were included: 15 patients received NB-UVB three times weekly (group I) and 15 patients received MTX 0.3 mg/kg per week (group II), both for 8 weeks. Before and after treatment, serum levels of IL-17 and IL-23 were investigated by ELISA technique and psoriasis area and severity index (PASI) was calculated. Results. After treatment, all patients showed a reduction in their PASI score, IL-17 and IL-23 serum levels with a nonsignificant difference between both therapeutic modalities (P value >0.05). A positive correlation was detected between the percent of reduction of IL-17, IL-23 and the percent of reduction of PASI score for patients receiving both treatments. No correlation was found between the percent of reduction of IL-17, IL-23 and duration of disease or age of all patients in this study. Conclusion. Interleukin-17 and IL-23 serum level may serve as a potential biomarker for predicting the prognosis and therapeutic response of NB-UVB or MTX in treating psoriasis.

An assessment of adalimumab efficacy in three Phase III clinical trials using the European Consensus Programme criteria for psoriasis treatment goals

The European Consensus Programme (ECP) established pan-European consensus definitions of psoriasis disease severity and treatment goals among 19 psoriasis experts from European nations. To use the ECP treatment goals to retrospectively assess adalimumab efficacy in patients who participated in Phase III clinical trials and met ECP criteria for moderate to severe psoriasis. Three trials were analysed: CHAMPION (n = 108), REVEAL (n = 814) and BELIEVE (n = 364). Moderate to severe psoriasis was defined as Dermatology Life Quality Index (DLQI) score > 10, with either > 10% body surface area involvement or Psoriasis Area and Severity Index (PASI) score > 10. Treatment goals were achieved with either treatment success (≥ 75% PASI score reduction) or intermediate response (PASI response ≥ 50% and < 75%) with DLQI ≤ 5. The percentages of patients who achieved treatment goals at week 16 in CHAMPION, REVEAL and BELIEVE were, respectively, (i) treatment success, 79·3%, 72·1% and 68·2%; (ii) intermediate response, 1·7%, 5·0% and 5·0%; or (iii) either goal, 81·0%, 77·1% and 73·2%. DLQI ≤ 5 at week 16 was achieved by 70·7%, 70·1% and 67·4% of patients, respectively. Differences between the percentages of adalimumab- vs. placebo-treated patients achieving treatment success were statistically significant (P < 0·001) from week 4 and week 8 of REVEAL and CHAMPION, respectively. Treatment success was achieved by > 93% of patients who attained treatment goals. At week 16 > 70% of patients achieved ECP treatment goals and met ECP criteria for continued treatment without modification. These results support the utility of ECP treatment goals for the assessment of therapeutic efficacy in moderate to severe psoriasis.

Pharmacogenetic Analysis of TNF, TNFRSF1A, and TNFRSF1B Gene Polymorphisms and Prediction of Response to Anti-TNF Therapy in Psoriasis Patients in the Greek Population

Although biologic therapies have revolutionized the treatment of psoriasis, patients exhibit a substantial heterogeneous response that could be due to complex genetic heterogeneity. The aim of this study was to investigate the possible influence of tumor necrosis factor-α (TNF), TNF receptor I (TNFRSF1A), and TNF receptor II (TNFRSF1B) gene polymorphisms on anti-TNF treatment responsiveness in psoriasis patients. A Greek multicenter collaboration was established to recruit a cohort of patients (n = 80) with psoriasis treated with anti-TNF drugs. Single nucleotide polymorphisms (SNPs) in TNF (-238G>A, -308G>A, -857C>T), TNFRSF1A (36A>G), and TNFRSF1B (676T>G) were genotyped by PCR-restriction fragment length polymorphism assays. SNPs and haplotypes, including stratification by comorbidity status, were analyzed for association with treatment response after 6 months of therapy, defined as a reduction in the Psoriasis Area and Severity Index (PASI) score by >75% (responders) or ≤50% (nonresponders). Sixty-three patients (78.8%) were defined as responders (PASI score reduction >75%) and 17 patients (21.2%) were defined as nonresponders (PASI score reduction ≤50%). Carriage of TNF -857C or TNFRSF1B 676T alleles was associated with positive response to drug treatment in patients treated with etanercept (p = 0.002 and p = 0.001, respectively). None of the genotyped SNPs were associated with responsiveness to treatment with infliximab or adalimumab. Additionally, when patients were stratified by comorbidity status, none of the genotyped SNPs were alone associated with responsiveness to drug treatment. This study is the first in the field of psoriasis demonstrating a strong association between genetic markers and positive response to drug treatment. Validation of this result in larger studies, as well as analysis of other drug treatments, could provide the basis for individually tailored treatment, along with increased cost effectiveness and reduced unnecessary exposure to toxicity.

Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): Why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis

Although there are many psoriasis assessment tools currently published, one of the unmet needs in psoriasis research remains consensus about the single best validated and reproducible assessment tool. In this systematic review we sought to determine the degree of correlation between two commonly used psoriasis assessment tools, the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Randomized controlled systemic trials in moderate to severe psoriasis were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We recorded and compared the percent of patients achieving both 75% reduction in PASI score (PASI 75) and PGA 0 or 1 (clear or almost clear) at 8 to 16 weeks, 17 to 24 weeks, and greater than 24 weeks of treatment with the investigational drug. Our literature review yielded 30 randomized controlled trials using biologic agents in moderate to severe psoriasis. We found that the two assessment tools correlate very tightly except at the lower bounds of therapeutic efficacy. The r(2) values for the correlation between PASI 75 and a score of clear or almost clear on the PGA were 0.9157 at 8 to 16 weeks and 0.892 at 17 to 24 weeks. Limitations of our study include the small number of randomized controlled trials publishing the percent of patients achieving 75% reduction in PASI score and a score of clear or almost clear on the PGA after 24 weeks of therapy. In addition, our results are not generalizable beyond the patients with moderate to severe plaque psoriasis. The two assessment tools are substantially redundant and either alone is a sufficient tool for assessing psoriasis severity in patients with moderate to severe disease. Because the PASI is better validated and more detailed, it remains the score of choice for clinical trials, but the simpler PGA may be well suited for community-based outcomes projects.

Mixed treatment comparison of a two-compound formulation (TCF) product containing calcipotriol and betamethasone dipropionate with other topical treatments in psoriasis vulgaris

Objective:The efficacy of the two-compound formulation (TCF) product containing calcipotriol and betamethasone dipropionate applied once daily in psoriasis has been demonstrated in phase III trials but no randomised clinical trial comparing all commonly used topical treatments exists. The aim of the study was to compare the efficacy of once-daily use of the TCF product relative to other commonly used topical agents in plaque psoriasis.Research design and methods:Data on change in Psoriasis Area and Severity Index (PASI) score from baseline and PASI 75 (percentage of patients achieving a 75% reduction in PASI score), after 4 weeks of treatment were obtained by means of a systematic literature review of randomised controlled trials and synthesised with a Bayesian mixed treatment comparison meta-analysis.Results:Relative to all active interventions, except for the unlicensed twice-daily application of the TCF product, the TCF once daily showed a greater efficacy based on PASI 75 response (relative risk ranging from 1.22 to 3.18) and improvement in PASI score from baseline (difference in % CFB PASI between TCF once daily and other active interventions ranged from 4.01 to 49.68).Conclusion:Among topical therapies evaluated, TCF once daily can be considered the most efficacious treatment for plaque psoriasis.

Psoriasis Therapy and Cardiovascular Risk Factors

Psoriatic patients present with an increased frequency of cardiovascular events. To study the impact of psoriasis duration and therapy on traditional and new cardiovascular risk factors. A longitudinal study performed between 2005 and the first trimester of 2008. Each patient was followed up for 12 weeks, and was observed before and 3, 6, and 12 weeks after starting therapy. Patients attending the Dermatology Service, University Hospital of Coimbra, Coimbra, Portugal were enrolled. Thirty-four patients with psoriasis vulgaris and 37 healthy volunteers as controls. Psoriasis Area and Severity Index (PASI); lipid profile, oxidized low-density lipoprotein (oxLDL), oxLDL/low-density lipoprotein (LDL), total antioxidant status, lipid peroxidation, C-reactive protein (CRP), and circulating levels of adiponectin. Ten patients started therapy with topical treatment, 11 with narrow-band UVB radiation (NB-UVB), and 13 with psolaren plus UVA (PUVA). Before starting therapy, psoriatic patients presented with several risk changes in their lipid profiles, and significantly higher CRP, oxLDL, and oxLDL/LDL, and lower adiponectin levels (vs control subjects), which may further contribute to inflammation and atherogenesis. After treatment of the patients, although no significant differences were observed in the lipid profile compared with baseline, some changes suggested that the treatment could somehow alter lipid metabolism, as the reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A and the increase in the atherogenic index cholesterol/HDL-C maintained an even higher significance (as shown by p-values) when compared with the control group. After topical therapy, there was a significant reduction in thiobarbituric acid reactivity only, suggesting that the reduction in the hyperproliferative process within the lesions is important for lipid peroxidation. After NB-UVB therapy, oxLDL/LDL, cholesterol/HDL-C, lipoprotein (a) [Lp(a)], and CRP remained higher than in the control subjects, reflecting persistent inflammation and atherogenic risk. After PUVA treatment, there was a significant reduction in Lp(a), associated with an almost significant increase in apolipoprotein-B (p = 0.054); these changes were not observed after NB-UVB treatment. However, after PUVA and NB-UVB treatment, CRP and, in the NB-UVB group, oxLDL/LDL were persistently higher than controls. Our data show that psoriatic patients present with several lipid profile changes that seem to be related to the severity of the disease and/or the treatment used. Mild psoriasis patients receiving topical treatment presented before starting therapy with a lipid profile similar to controls, whereas those undergoing NB-UVB and PUVA, who had higher PASI scores, presented with several risk factors. Moreover, PUVA therapy seems to interact in a different way with lipids that might result from an interaction of psoralen with plasma lipids, namely Lp(a). Inflammation, a hallmark of psoriasis, also seems to be related to psoriasis severity. Both NB-UVB and PUVA were effective, as shown by the reduction in PASI score, as well as in the oxidative and inflammatory stress markers. However, after NB-UVB and PUVA, a low-grade inflammatory process still persisted, which might be related to the duration of remission of the disease.

Vitamin D status in psoriasis patients during different treatments with phototherapy

Background Phototherapy (broadband UVB (BUVB), narrowband UVB (NBUVB) and heliotherapy) is commonly used treatment modalities for widespread psoriasis. Vitamin D3, cholecalciferol, is produced in the epidermis by ultraviolet radiation (290–315 nm) of 7-dehydrocholesterol. 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D [1,25(OH) 2D] are the major circulating metabolites. Sun exposure is the strongest factor influencing 25(OH)D. The similar wavelength spectrum of UVB responsible for D vitamin synthesis (BUVB, 280–315 nm) has been successfully used for years to treat psoriasis. Purpose The aim was: (1) To increase the knowledge about the effects of phototherapy on vitamin D production during treatment of psoriasis. (2) To examine if there were differences between the effect of BUVB, NBUVB and heliotherapy on vitamin D synthesis in psoriasis patients. Methods Serum concentrations of 25(OH)D, 1,25(OH) 2D, PTH, calcium and creatinine, measured before and after phototherapy in white Caucasian patients with moderate to severe active plaque psoriasis, were aggregated from three studies. Results Psoriasis improved in all patients, with a reduction in PASI ((Psoriasis Area and Severity Index) score of about 75% on all regimes. Serum 25(OH)D increased and PTH decreased after the phototherapy. The increase in 25(OH)D was higher in the BUVB treated patients compared with NBUVB. There was no correlation between the dose of UVB and the increase of 25(OH)D. Conclusion UVB and heliotherapy improved the psoriasis score, increased the serum 25(OH)D levels and reduced the serum PTH concentrations. Vitamin D production in psoriasis patients increased less with NBUVB than with BUVB phototherapy.

A case report of a psoriatic arthritis patient on hemodialysis treated with tumor necrosis factor blocking agent and a literature review

This report seeks to describe the clinical efficacy and safety of infliximab in a patient with psoriatic arthritis on hemodialysis and to review the literature on the topic. We present a patient with psoriatic arthritis on hemodialysis treated with infliximab and we review the literature. Our case includes a patient with severe psoriasis and dactylitis with chronic renal failure requiring regular hemodialysis. At presentation the patient had a psoriasis area and severity index (PASI) score of 35.1 and dactylitis affecting the right thumb. Evaluation of laboratory parameters revealed a slight increase of erythrocyte sedimentation rate (21 mm/h) and a mild normocytic anemia (Hct 36.4). The rest of the laboratory and imaging tests were within normal limits. Infliximab was initiated at the loading dose of 5 mg/kg body weight at weeks 0, 2, 6, and every 8 weeks thereafter. On retreatment at week 14 the PASI score was measured to 3.4. After the conclusion of 6 months of treatment, the reduction of PASI score was sustained reaching the point of 0.8. In addition, dactylitis, as well as laboratory parameters, showed a striking improvement. On the other hand, during the same period of time, no changes of renal functions were noted and no complications were reported and the patient continued his hemodialysis on a regular basis. Our case is in accordance with other reports supporting that infliximab treatment in patients undergoing hemodialysis can be safe, well tolerated, and effective. However, larger trials are needed to prove its use in these patients.

Evolución clínica de los pacientes psoriásicos tratados con efalizumab al suspender el fármaco

Introduction In February 2009, the European Medicines Agency suspended the marketing authorization for efalizumab after 3 confirmed cases of progressive multifocal leukoencephalopathy were reported. To assess the consequences of this decision, we performed a prospective follow-up study of patients in our department who were being treated with efalizumab at the time and compared clinical outcomes with data from the literature. Patients and methods Thirty-two patients (28 with plaque psoriasis and 4 with palmoplantar psoriasis) were enrolled between February and March 2009. We recorded psoriasis area and severity index (PASI) scores at the moment of efalizumab discontinuation, at 6 weeks post-discontinuation, and at 3-monthly intervals thereafter. PASI scores prior to treatment with efalizumab were also noted. For patients who experienced rebounds with generalized psoriasis, we noted the time that had elapsed since efalizumab discontinuation and the treatment they were receiving. Results Even though 92.8% of the patients were considered good responders (>75% reduction in PASI score), 25% of the group (8/32) experienced rebound and 15.7% (5/32) experienced relapse. The percentage of patients in whom rebound was observed on transition therapy was 18% (2/11) for cyclosporin, 50% (1/2) for methotrexate, 50% (1/2) for adalimumab, 50% (1/2) for etanercept, and 27% (3/11) for topical treatment. Conclusions We observed a very high rate of rebound and generalized inflammation in patients whose disease had previously been well controlled for several years.

The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: A randomized clinical trial

Psoriasis is associated with health-related quality-of-life impairment and depression. We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis. Patients with moderate to severe psoriasis in a randomized, placebo-controlled, double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination (ET) using the Zung Self-rating Depression Scale (ZDS). The effects of adalimumab (40 mg every other week) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance. Relationships between ZDS and the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index, and the Short Form 36 Health Survey were assessed using Pearson correlations. Changes in ZDS score were compared for patients with and without a 75% or greater reduction in baseline PASI score. Compared with the placebo group (n = 52), the adalimumab group (n = 44) experienced an additional 6-point reduction in ZDS score (95% confidence interval: 2.5-9.5; P < .001) by week 12/ET. Depression improvement was correlated with improvement in PASI (r = 0.5; P < .0001) and Dermatology Life Quality Index (r = 0.5; P < .0001). Greater ZDS score improvement was observed at week 12/ET in responders with a 75% or greater reduction in baseline PASI score than in nonresponders (10.6 [SD = 9.4] vs 1.4 [SD = 9.6]; P < .001). This analysis cannot distinguish whether adalimumab has a direct or indirect effect on depression. Adalimumab treatment reduced psoriasis symptoms, reduced depression symptoms, and improved health-related quality of life in patients with moderate to severe psoriasis.

New drugs: Ustekinumab, tocilizumab, and telavancin hydrochloride

Agent for psoriasis Psoriasis is an autoimmune disease characterized by inflammatory skin lesions/plaques that are often painful and can be debilitating. Although milder forms of psoriasis can often be effectively treated with topical corticosteroids and other topically applied agents, moderate to severe forms of the disease often require systemic therapy or phototherapy. Advances in the treatment of psoriasis have included the use of medications that have immunosuppressive activity such as methotrexate; cyclosporine; alefacept (Amevive), which interferes with T-cell activation; and the tumor necrosis factor (TNF) antagonists etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). Interleukin (IL)-12 and -23 are naturally occurring proteins that are involved in the psoriatic inflammatory process by activating natural killer cells and T-cells. Ustekinumab (Stelara—Centocor Ortho Biotech) is a human monoclonal antibody that is the first medication to selectively bind to these cytokines. It binds with high affinity to the p40 protein subunit of IL-12 and -23, thereby preventing them from binding with their respective receptors and resulting in a decreased inflammatory response. The new drug is indicated for the treatment of adult patients with moderate or severe plaque psoriasis who are candidates for phototherapy or systemic therapy. The efficacy of ustekinumab was demonstrated in two placebo-controlled studies in which approximately 70% of the patients treated with the drug experienced at least a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) after two doses compared with less than 5% of those receiving placebo. In one of these studies, patients were evaluated for a longer period and approximately 90% of the patients having an initial reduction in PASI score of at least 75% maintained this response through 1 year of treatment. In a study in which ustekinumab was compared with etanercept, 68% and 74% of patients treated with 45 and 90 mg ustekinumab dosages, respectively, experienced at least a 75% reduction in PASI score compared with 57% of the patients treated with etanercept. Of the patients who did not have a response to etanercept, almost 50% had at least a 75% reduction in PASI score within 12 weeks following subsequent treatment with ustekinumab. The risks and adverse events associated with the use of ustekinumab are generally similar to those of the TNF antagonists. Of greatest concern is the potential for serious infection, and treatment with ustekinumab should not be initiated in patients with a clinically important active infection. If a serious infection develops during treatment, treatment with ustekinumab should be suspended until the infection is adequately treated or resolves. Patients should be evaluated for the presence of a tuberculosis (TB) infection before initiating treatment with ustekinumab. The drug should not be used in patients with active TB, and if latent TB is identified, antitubercular treatment should be initiated before administering ustekinumab. Individuals who have a genetic deficiency of IL-12 and -23 are at greater risk of disseminated infections caused by mycobacteria, salmonella, and Bacillus CalmetteGuerin (BCG) vaccinations. Whether patients experiencing inhibition of these ILs as a result of ustekinumab treatment will be more vulnerable to these infections is not known. However, it is recommended that BCG vaccines not be administered during treatment with ustekinumab or for 1 year before initiating treatment or 1 year following discontinuation of treatment. Before initiating treatment with ustekinumab, patients should have already received the immunizations recommended by current guidelines, and they should not receive live vaccines during treatment. Like other medications that exhibit an immunosuppressant action, ustekinumab may increase the risk of malignancies. The safety of its use in patients who have a known malignancy or a history of malignancy has not been evaluated. In the clinical studies with ustekinumab, which included more than 3,500 patients, one patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Treatment was discontinued, and the patient fully recovered with appropriate management. If neurologic or other manifestations suggestive of RPLS occur in patients treated with the new drug, therapy should be discontinued. The adverse events experienced most often in the clinical studies with ustekinumab include nasopharyngitis (7%), headache (5%), upper respiratory tract infection (4%), and fatigue (3%). As with all biological therapies, a concern exists regarding immunogenicity. Because ustekinumab has such a long half-life and its presence in the blood interferes with the antibody assay, many of the test results were inconclusive. Of the approximately 2,000 patients screened, less than 5% had positive antibody results, indicating a low risk of immunogenicity. Ustekinumab is classified in Pregnancy Category B and should only be

Sulfasalazine and pentoxifylline in psoriasis: A possible safe alternative

Background: Conventional therapy of extensive psoriasis is effective but has complications. Biologics are safer but expensive. Objective: To assess the efficacy of sulfasalazine and pentoxifylline, which have TNF antagonizing and anti-proliferative action in the treatment of psoriasis. Methods: In this randomized controlled trial, 32 patients with extensive psoriasis were divided into four groups: group A received sulfasalazine; group B received pentoxifylline; group C received both drugs; and group D received methotrexate. The Psoriasis Area and Severity Index (PASI) score was done at weeks 0, 2, 4, 6 and 8. Results: A significant reduction in PASI score occurred in groups C and D (p = 0.043 and 0.018, respectively). A significantly higher percentage of PASI score reduction occurred in group D compared with groups A, B and C (p = 0.006, 0.003 and 0.030, respectively). An excellent response occurred in one patient (14.3%) in group D. A very good response occurred in two patients (22.2%) in group C, and in five patients (71.4%) in group D. A moderate response occurred in three patients (37.5%) in group A, one patient (12.5%) in group B, and one patient (14.3%) in group D. Conclusion: Although incomparable to methotrexate, combined sulfasalazine and pentoxifylline produced a good response in cases of extensive psoriasis. Multicentre studies are needed to validate these results.

Clinical Outcomes in Patients With Psoriasis Following Discontinuation of Efalizumab Due to Suspension of Marketing Authorization

Introduction In February 2009, the European Medicines Agency suspended the marketing authorization for efalizumab after 3 confirmed cases of progressive multifocal leukoencephalopathy were reported. To assess the consequences of this decision, we performed a prospective follow-up study of patients in our department who were being treated with efalizumab at the time and compared clinical outcomes with data from the literature. Patients and methods Thirty-two patients (28 with plaque psoriasis and 4 with palmoplantar psoriasis) were enrolled between February and March 2009. We recorded psoriasis area and severity index (PASI) scores at the moment of efalizumab discontinuation, at 6 weeks post-discontinuation, and at 3-monthly intervals thereafter. PASI scores prior to treatment with efalizumab were also noted. For patients who experienced rebounds with generalized psoriasis, we noted the time that had elapsed since efalizumab discontinuation and the treatment they were receiving. Results Even though 92.8% of the patients were considered good responders (>75% reduction in PASI score), 25% of the group (8/32) experienced rebound and 15.7% (5/32) experienced relapse. The percentage of patients in whom rebound was observed on transition therapy was 18% (2/11) for cyclosporin, 50% (1/2) for methotrexate, 50% (1/2) for adalimumab, 50% (1/2) for etanercept, and 27% (3/11) for topical treatment. Conclusions We observed a very high rate of rebound and generalized inflammation in patients whose disease had previously been well controlled for several years.

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 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.