Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis

A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis. Many consider this endpoint to be too stringent as it places potentially useful therapies at risk of failing to demonstrate efficacy. We hypothesized that a 50% reduction in the PASI score (PASI 50) represents a meaningful change in a person's life and thus is a better primary endpoint. To test this hypothesis, we analyzed PASI scores, quality of life (QoL) data, and desired re-treatment scores from a number of clinical trials in addition to studying individual elements that make up the PASI. This analysis shows (1). the PASI score is not linearly reflective of psoriasis severity (eg, a reduction in area of 95% without a change in redness, scaliness, and induration translates to only a 66% reduction in PASI); conversely, a drop in erythema, scale, and induration from an average of 3 to 1 would not lead to a 75% reduction in PASI; (2). treatment with methotrexate, an effective psoriasis therapy, more frequently reaches PASI 50 than PASI 75 as evidenced by a recent open trial in which 63% of patients achieved PASI 50 versus 26% achieving PASI 75; (3). improvement in QoL exists at PASI 50, using the Dermatology Quality of Life Index, as documented in several recently completed large clinical trials; (4). patients achieving PASI 75 frequently defer therapy until they are well below PASI 50; a clinical trial where retreatment was patient initiated showed patients did not re-treat until their PASI dropped to an average of 20% improvement from baseline; and (5). effective, meaningful therapies are consistently differentiated from placebo at PASI 50 as evidenced by histologic and photographic parameters of clinical trials of alefacept, efalizumab, and etanercept. We conclude that PASI 50 equates to a clinically meaningful improvement in psoriasis and represents a discerning primary endpoint.     

Time,Psoriasis Area and Severity Index and Dermatology Life Quality Index of patients with psoriasis who drop out of clinical trials on etanercept because of lack of efficacy: a pooled analysis from 10 clinical trials

Psoriasis is a common skin disease, and clinical trials are a way of measuring how effective different treatments for psoriasis are. During such trials, researchers generally use specific methods for measuring improvements in patients’ symptoms and quality of life. These include the Psoriasis Area Severity Index (PASI, for which the lower the score, the worse the severity of the disease), the Physician Global Assessment (PGA) and the Dermatology Life Quality Index (DLQI). If a treatment has not become effective by a certain time point, it may increase the likelihood of patients being dissatisfied and leaving a clinical study. In this study, the researchers looked at clinical trials involving a drug for psoriasis called etanercept, to learn more about the number of patients who drop out due to ‘lack of efficacy’, when they most commonly do so, and how this relates to their PASI and DLQI. Of 6119 patients taking part in the studies looked at, 128 dropped out due to ‘lack of efficacy’. The highest increase of patients dropping out happened between Day 75 and 85. The lowest PASI score of patients dropping out was 6.3 within 120 days. Dropouts who achieved ≥ PASI 75 were rare. The authors conclude that around Day 80 is the critical time when many patients might have lost their willingness to wait for their treatment with etanercept to show a better effect. Most of the patients dropping out had experienced little or no improvement, or worsening of their psoriasis.     

Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis

OBJECTIVE: To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly. DESIGN, SETTING, AND PATIENTS: A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005. INTERVENTIONS: Patients were randomized to receive placebo or etanercept for 12 weeks. Beginning with week 13, all patients (N=591) received etanercept. MAIN OUTCOME MEASURES: Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis. RESULTS: Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and etanercept treatments. Nonneutralizing antibodies to etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%. CONCLUSIONS: Extended exposure to 50 mg of etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy. Trial Registration clinicaltrials.gov Identifier NCT00111449.     

Clear or almost clear skin improves the quality of life in patients with moderate‐to‐severe psoriasis: a systematic review and meta‐analysis

Psoriasis Area and Severity Index (PASI) 75 response is currently considered the gold standard for assessing treatment efficacy in moderate‐to‐severe psoriatic patients. PASI 90 response denotes better clinical improvement compared to PASI 75. Very few studies have assessed if a greater PASI clinical response is associated with greater improvements in Dermatology Life Quality Index (DLQI). A systematic review and meta‐analysis was performed to assess the association between PASI response and DLQI. The study was conducted to assess whether greater improvement in PASI scores from PASI 75–89 to PASI 90 is associated with greater Quality of life (QoL) improvements, specifically DLQI scores. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane Library to identify studies evaluating biologic interventions in adult moderate‐to‐severe psoriasis patients reporting PASI response and their corresponding DLQI change from baseline score. The quality of evidence was assessed through Jadad score for randomized controlled trials and Downs and Black's checklist for observational studies. Meta‐analysis estimated change from baseline in DLQI for PASI 75–89 responders to be 78% (95% credible intervals [CrI]: 75–82%) and for PASI 90 responders to be 90% (95% CrI: 88–93%). This implies 12% greater improvement in DLQI score for PASI 90 responders compared with PASI 75–89 responders. In addition, the meta‐analysis also showed a statistically significant difference in DLQI score of 0/1 between PASI 75‐89 and PASI 90 responders (45% [95% Crl]; 41.0–50.0% and 73% [95% Crl]; 70.0–76.0%), respectively, Bayesian P < 0.0001). In conclusion, substantial improvement in clinical efficacy is associated with improved QoL in patients with moderate‐to‐severe psoriasis suggesting that PASI 90 responders (clear or almost clear skin) could achieve a superior QoL compared to PASI 75–89 responders.     

Economic evaluation of etanercept in the management of chronic plaque psoriasis

Background  The National Institute for Health and Clinical Excellence has recommended that etanercept 25 mg twice weekly (biw) be used in adults with severe plaque psoriasis. However, its economic model did not consider the alternative licensed regimen of etanercept 50 mg biw.
Objectives  To assess the cost-effectiveness of etanercept 50 mg biw for the treatment of chronic plaque psoriasis, and to explore characteristics of patients who benefited most from 50 mg dosing.
Methods  An economic model was constructed to estimate the incremental cost per quality-adjusted life year (QALY) gained. The model considered patients with chronic plaque psoriasis who had both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) of 10 or higher who were unable to take standard systemic therapies. Quality of life gain was estimated from the DLQI responses of patients enrolled in three clinical studies. The model considered expenditure on drugs, monitoring visits, adverse events and inpatient stays. Costs were estimated from the perspective of the U.K. National Health Service over a time period of 10 years.
Results  The incremental cost per QALY for etanercept 50 mg biw compared with no systemic therapy was found to be £6217 (95% confidence interval £5396–7486). The cost-effectiveness of 50 mg dosing was more attractive in patients with baseline PASI ≥ 20 (£5163) or baseline DLQI ≥ 20 (£4599).
Conclusions  This model found the licensed dose regimen of etanercept 50 mg biw to be cost effective in the U.K. This regimen was particularly appropriate for patients with severe disease or poor quality of life at baseline.     

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.     

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept

BACKGROUND: Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. OBJECTIVES: To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. METHODS: Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. RESULTS: All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the treatment. Skin histological abnormalities showed statistically significant modifications during treatment (P < 0.001). Immunohistochemical expression of CTACK/CCL27 decreased significantly (P < 0.001) and its relation with final PASI score was statistically significant (P < 0.05); the pattern of distribution of CTACK/CCL27 immunoreactivity significantly moved from diffuse and predominantly suprabasal to basal (P < 0.001) and the restoration of basal distribution of CTACK/CCL27 was also significantly related to clinical improvement of cutaneous disease (P < 0.001). CONCLUSIONS: Etanercept induces a clinical and histological improvement of psoriatic disease, promoting a reduction in CTACK/CCL27 cutaneous immunostaining and favouring the restoration of physiological CTACK/CCL27 epidermal expression. Moreover, CTACK/CCL27 reduction in cutaneous expression during administration of etanercept could be considered a favourable prognostic marker.     

Dramatic impact of a Psoriasis Area and Severity Index 90 response on the quality of life in patients with psoriasis: an analysis of Japanese clinical trials of infliximab

European S3 Guidelines on the systemic treatment of psoriasis in 2009 propose 75% or more improvement in the Psoriasis Area and Severity Index from baseline (PASI 75) and a Dermatology Life Quality Index (DLQI) of 0 or 1 as treatment goals. However, the relationship of these two parameters is yet to be clarified. Herein, we analyzed the data pooled from two Japanese phase III clinical trials on psoriasis with infliximab to clarify the PASI response necessary to achieve a DLQI of 0 or 1. Of the 90 patients, the mean percent improvement in PASI at week 50 or 66 was 74.5%, and the PASI 75 and PASI 90 response rates were 66.7% and 46.7%, respectively; no difference in the improvement was noted among the body areas. Significant improvements in nail psoriasis were also observed. A negative correlation was shown between the improvement in PASI and DLQI. Patients who achieved a PASI 90 response had a significantly higher percentage of achieving a DLQI of 0 or 1 than the patients who achieved a PASI 75 but not a PASI 90 response. The median serum trough level of infliximab was maintained at 2 μg/mL or more in the PASI 90 responders, whereas it was less than 1 μg/mL at week 30 and on in the others. The present results demonstrate that a PASI 90 response is necessary to achieve a DLQI of 0 or 1. Infliximab is considered a useful drug in meeting the treatment goal of achieving a DLQI of 0 or 1 through the attainment of a PASI 90 response.     

The relationship between quality of life and skin clearance in moderate-to-severe psoriasis: lessons learnt from clinical trials with infliximab

The physical presentation of psoriasis and its impact on health-related quality of life (HRQoL) varies greatly between patients as well as over the course of the disease. A number of instruments have been developed for evaluating disease severity and its impact on HRQoL, the best known being the Psoriasis Area and Severity Index (PASI). HRQoL is most commonly evaluated using the Dermatology Life Quality Index (DLQI) and/or the Short-Form-36 Health Survey (SF-36). The exact correlation between the reduction of skin symptoms upon therapy and changes of HRQoL is not known. Since improvement of HRQoL is being established as an independent goal of psoriasis therapy, a better understanding of the relationship between skin symptoms and HRQoL during treatment will likely influence not only disease concepts but also physicians treatment decisions. Based on a selective review of the literature, this paper focuses on recent insight obtained from clinical trials with infliximab on the correlation between skin clearance and changes of HRQoL in psoriasis and compares these findings with results from studies with other biologics. Together these data indicate that despite the lack of a direct correlation between absolute PASI and DLQI values, significant reductions of PASI are likely to correlate with significant improvements of HRQoL. There is also evidence, that large improvements of HRQoL as currently discussed as treatment goals in psoriasis are primarily achieved in patients with an at least 75% reduction of their PASI.     

Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure,secondary failure or intolerance to etanercept

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.     

Cost‐effectiveness of psoriasis therapy with etanercept in Germany

Background: We estimated the cost‐effectiveness of intermittent therapy with etanercept in patients with moderate‐to‐severe plaque‐type psoriasis in comparison to non‐systemic therapy in Germany. Patients and Methods: We performed a cost‐utility analysis using the endpoint costs per quality‐adjusted life year gained (costs/QALY). For this purpose, we adapted a UK‐based Markov model by means of resource use data that we derived from a German cost study. Efficacy data, information on frequency of adverse events and changes in quality of life were derived from three pooled clinical trials. We extrapolated the further course of the disease and its treatment over a 10 year course. Results: For patients with an initial Psoriasis Area and Severity Index (PASI) > 10 and a Dermatology Life Quality Index (DLQI) > 10 the incremental cost‐effectiveness ratio (ICER) for etanercept compared to non‐systemic therapy was 45,491 €/QALY. For patients with PASI and DLQI > 15 costs/QALY were 32,058 € and among patients with severe plaque psoriasis (DLQI and PASI > 20) 18,154 € . Conclusions: According to internationally accepted levels of cost‐effectiveness thresholds, the intermittent treatment of (moderate to) severe plaque‐type psoriasis with etanercept is a cost‐effective measure within the German healthcare system.     

Etanercept improves the health-related quality of life of patients with psoriasis: results of a phase III randomized clinical trial

In this randomized, double-blind, phase III trial, patients with psoriasis received etanercept for 24 weeks or placebo for 12 weeks followed by etanercept for 12 weeks. At week 12, improvement in Dermatology Life Quality Index was 47% to 61% with etanercept compared with 11% with placebo (P < .0001). Etanercept rapidly and substantially improved patients' health-related quality of life.     

Efficacy of systemic therapies for moderate‐to‐severe psoriasis: a systematic review and meta‐analysis of long‐term treatment

Background Despite the chronicity of psoriasis, most systematic reviews focus on short‐term treatment. Methods The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta‐analysis. Particular attention was paid to statistical approaches of handling dropouts. Results A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta‐analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72–83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71–83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45–74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52–72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34–56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49–62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42–57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. Conclusions More sufficient data is required to draw reliable conclusions in extended long‐term treatment and head‐to‐head comparisons are necessary.     

Cost-effectiveness analysis of TNF-α blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-α agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48–50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48–50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.     

A randomized trial of etanercept as monotherapy for psoriasis

OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Outpatient, ambulatory; private practice and university dermatology research centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug. INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.     

Correlation between Dermatology Life Quality Index and Minor test and differences in their levels over time in patients with axillary hyperhidrosis treated with botulinum toxin type A

Hyperhidrosis is an idiopathic condition of exaggerated sweat production resulting in dramatic impairments of daily activities, social interactions and occupational activities. The aim of the present study was to evaluate correlation between a subjective (Dermatology Life Quality Index) and an objective (Minor test) criterion and to assess difference in their levels over time in patients affected by axillary hyperhidrosis treated with botulinum toxin type A. Nineteen patients received injections of 50 U of botulinum toxin type A per axilla. Patients were observed for 9 months after treatment. All patients showed great improvement of hyperhidrosis by Minor test and Dermatology Life Quality Index following treatment with botulinum toxin type A, with the effect persisting for 6-9 months. All patients demonstrated direct relationship between objective improvement documented by Minor test and quality of live improvement documented by Dermatology Life Quality Index after treatment with botulinum toxin type A.     

A randomized, ‘head‐to‐head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB‐UVB) phototherapy in obese psoriasis patients

Background Etanercept is a tumour necrosis factor‐alpha antagonist used for the treatment of moderate‐to‐severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB‐UVB) phototherapy is unaffected by body weight and the addition of NB‐UVB to etanercept therapy may supplement the efficacy of etanercept in these patients. Objective To evaluate the efficacy and safety of NB‐UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate‐to‐severe plaque psoriasis. Methods Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, ‘head‐to‐head’ comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB‐UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician’s Global Assessment (PGA) scores. Results Twenty‐five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB‐UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively). Conclusion Combination etanercept and NB‐UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB‐UVB.     

Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial

This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.     

Effects of alefacept on health-related quality of life in patients with psoriasis: results from a randomized,placebo-controlled phase II trial

Introduction

Chronic plaque psoriasis has a profound impact on patient quality of life (QOL), including adverse psychosocial effects, impaired daily activities, anxiety, and depression.

Objective

To assess health-related QOL in a randomized phase II trial of alefacept (human LFA-3/IgG₁ fusion protein), a selective immunomodulator for psoriasis.

Study design

Multicenter, randomized, placebo-controlled, double-blind trial.

Methods

229 patients with moderate to severe psoriasis were randomized to alefacept (0.025, 0.075, or 0.150 mg/kg) or placebo by 30-second intravenous bolus once weekly for 12 weeks and followed for 12 additional weeks. Patients completed a general (SF-36®¹ Health Survey) and dermatology-specific (Dermatology Life Quality Index [DLQI] and Dermatology Quality Of Life Scales [DQOLS]) QOL surveys at each study visit.

Results

Patients treated with alefacept had significantly greater improvements on dermatology-specific QOL scales compared with patients receiving placebo (p < 0.05). Patients who achieved a ≥50% or a ≥75% reduction in Psoriasis Area and Severity Index (PASI) reported similar improvement in QOL, which was significantly greater than that of other patients.

Conclusions

The clinical effect of alefacept on psoriasis is associated with an improvement in patients’ QOL. Among patients with moderate to severe psoriasis, an improvement in PASI of 50% or more is associated with better QOL scores.