Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P = 0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.     

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry

Background Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. Objectives To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. Methods Data from a psoriasis registry ( http://www.psoriasis‐therapieregister.at ) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5‐methoxypsoralen (5‐MOP; n = 32) and 8‐methoxypsoralen (8‐MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8‐MOP and 5‐MOP, respectively) and at week 12 for biologics. Results Intention‐to‐treat–as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post‐hoc modified worst‐case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. Conclusions Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head‐to‐head studies of PUVA and biologics are warranted to confirm these observations.     

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland

Background There are limited data on the use of ustekinumab outside of clinical trials. Objectives To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. Methods A retrospective case‐note review of 129 patients with psoriasis treated with ustekinumab. Results Baseline Psoriasis Area and Severity Index (PASI) was 22·9 ± 10·1 (mean ± SD). After 16 weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n = 80/127) of patients, although four patients required concomitant therapy at the 16‐week time point. Previous biologic use did show a small, non‐significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n = 5/17) of individuals weighing 90–100 kg and treated with the standard 45 mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups < 80, 80–90, 100–110 and > 110 kg, respectively (P = 0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n = 3/129) of patients. Conclusions Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short‐term therapeutic efficacy with an acceptable short‐term safety profile.     

Estimation of tissue osteopontin levels before and after different traditional therapeutic modalities in psoriatic patients

Background Several lines of evidences support a major role for Th1 cells in psoriasis. Treatment of psoriasis with cyclosporine, methotrexate and psoralen plus ultraviolet A (PUVA) is associated with clinical improvement and decrease in epidermal hyperplasia. Osteopontin (OPN) exerts a T‐helper type 1 (Th1) cytokine function, regulating inflammatory cell accumulation and function. Objective To detect the effects of methotrexate, cyclosporine and PUVA on OPN expression in psoriatic plaques, and whether these changes correlate with clinical response. Methods For three groups of psoriatic patients (each including 12 patients), the Psoriasis Area Severity Index (PASI) and levels of lesional skin OPN were determined using enzyme‐linked immunosorbent assays before and after treatment with methotrexate, cyclosporine or PUVA. Skin biopsies from 20 healthy volunteers served as control for OPN levels in normal skin. Results Baseline lesional skin of psoriatic patients showed a statistically significant elevation of OPN levels in comparison to controls. Three months after therapy, the three therapeutic modalities were associated with a significant decrease in the mean levels of PASI and tissue OPN, with the PUVA group showing the highest level of reduction in OPN levels and cyclosporine group showing the highest level of reduction in PASI. Conclusion Our study points to the possible role played by OPN in the pathogenesis of psoriasis and in reflecting disease severity. These standard therapeutic modalities used in the current study were associated with a significant decrease in PASI and OPN levels. They constitute highly effective therapeutic modalities for psoriasis, which might exert their anti‐psoriatic activity partially through altering the expression of OPN.     

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis

Background Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D₃ synthesis. Objective The aim of the study was to investigate the effect of climate therapy on vitamin D₃ synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. Methods Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24–65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8–18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients’ individual skin UV doses based on UV measurements were estimated. Results Sun exposure for 15 days lead to a 72.8% (± 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25‐hydroxyvitamin D [25(OH)D] increased from 57.2 ± 14.9 nmol/L before therapy to 104.5 ± 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)₂D] increased from 146.5 ± 42.0 to 182.7 ± 59.1 pmol/L (P = 0.01); the ratio of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A₁c (HbA₁c) levels decreased from 5.6 ± 1.7% to 5.1 ± 0.3% (P < 0.0001). Conclusion Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.     

Expression of dipeptidyl-peptidase IV (CD26) on CD8+ T cells is significantly decreased in patients with psoriasis vulgaris and atopic dermatitis

T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2-terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P<0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%+/-3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%+/-3.7, mean and SD, n=15) compared to the control population (11.58%+/-5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.     

Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis,cutaneous T‐cell lymphoma and psoriasis in combination with serum thymus and activation‐regulated chemokine levels

Background CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T‐cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. Objective To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation‐regulated chemokine (TARC). Methods Serum sCD26 levels were measured using enzyme‐linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. Results Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 ± 51.5 ng/mL and they were significantly lower than those with early stage (193.1 ± 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2–73.7%, 81.4–97.6%, 65.2–94.4%, and 81.4–88.9% respectively. Conclusion Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis.     

Plasma homocysteine and folate levels in patients with chronic plaque psoriasis

Background Hyperhomocysteinaemia is a well‐known risk factor for cardiovascular diseases. Patients with severe chronic plaque psoriasis have a higher risk of death due to arterial and/or venous thrombosis. Objectives To investigate the relationship among plasma homocysteine and folate levels and severity of chronic plaque psoriasis in a selected cohort of patients with psoriasis without known risk factors for acquired hyperhomocysteinaemia. Methods We performed a case–control study in 40 patients with chronic plaque psoriasis and 30 age‐ and sex‐matched healthy controls. Cases and controls were selected excluding individuals with conditions or diseases associated with acquired hyperhomocysteinaemia, and were also asked to stop alcohol and coffee consumption for 1 week before blood sampling. The plasma levels of homocysteine and folic acid were measured and were correlated with the severity of psoriasis (Psoriasis Area and Severity Index, PASI). Results Patients with psoriasis had plasma homocysteine levels higher than controls (mean ± SD 16·0 ± 5·6 vs. 10·4 ± 4·7 μmol L^?1; P < 0·001). Conversely, folic acid levels were lower in patients with psoriasis compared with controls (mean ± SD 3·6 ± 1·7 vs. 6·5 ± 1·7 nmol L^?1; P < 0·001). Plasma homocysteine levels in patients with psoriasis correlated directly with disease severity (PASI) and inversely with folic acid levels. Plasma folic acid levels were inversely correlated with the PASI. No abnormalities of plasma vitamin B₆ and B₁₂ were found. Conclusions Patients with psoriasis may have a tendency to hyperhomocysteinaemia, which may predispose to higher cardiovascular risk. Dietary modification of this risk factor appears relevant to the global management of patients with moderate to severe psoriasis.     

Narrowband ultraviolet B versus psoralen plus ultraviolet A therapy for severe plaque psoriasis: an Indian perspective

There is a dearth of studies comparing the efficacy of psoralen ultraviolet A (PUVA) and narrowband (NB)‐UVB in psoriasis in South Asian patients. Patients having plaque psoriasis with > 20% body surface area involvement were randomly assigned to one of two groups (group A: NB‐UVB, group B: PUVA). The response to treatment was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and every 2 weeks thereafter. The maximum possible treatment duration was 16 weeks. In total, 43 patients (21 NB‐UVB, 22 PUVA) completed the study. Marked improvement was seen in 80.9% of the patients in group A and 81.8% in group B (NS: P > 0.05). The mean ± SD time taken to achieve marked improvement was 9.9 ± 3.3 and 9.9 ± 3.5 weeks, respectively. In total, 29 patients were available for the analysis of the remission data at 6 months after treatment completion; 26.7% of the patients in group A and 42.8% in group B were in remission (NS: P > 0.05). Both methods seem to be equally effective in achieving clearance and maintaining remission of severe chronic plaque psoriasis in patients with Fitzpatrick skin type 4 and 5.     

Soluble intercellular adhesion molecule-1 levels in patients with psoriasis

A newly developed ELISA was used to detect and quantify the presence of a soluble form of intercellular adhesion molecule-1 (sICAM-1) in the circulation of healthy individuals compared with patients with psoriasis vulgaris. Seventeen psoriatic patients were studied. The extent of skin lesions was rated by the psoriasis area and severity index (PASI). Seventeen age- and sex-matched healthy individuals served as controls. Serum levels were measured by an ELISA technique utilizing an anti-ICAM-1 murine monoclonal antibody bound to the solid phase, and a second, peroxidase-conjugated monoclonal antibody reacting with sICAM-1. Serum levels in controls were 358.8±87.9 ng/ml sICAM-1, and 480.5±133.6 ng/ml in psoriatics (mean±SD; P=0.02). In psoriasis. sICAM-1 levels were found to be directly proportional to the PASI score (y=363.002 + 8.525x, R=0.55. P=0.021). These data suggest that the concentration of sICAM-1 in serum increases during psoriatic inflammation. The origin and function of sICAM-1 in psoriasis remain to be defined.     

Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial

Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24‐week, randomized, controlled, investigator‐blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg^?1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg^?1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg^?1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.     

Bath psoralen+ultraviolet A photochemotherapy vs. narrow band‐ultraviolet B in psoriasis: a comparison of clinical outcome and effect on circulating T‐helper and T‐suppressor/cytotoxic cells

Background: Comparative success rates of bath psoralen+ultraviolet A (PUVA) and narrow band‐ultraviolet B (NB‐UVB) in psoriasis treatment are variably reported with no previous studies on the possible effect of bath PUVA on circulating CD4+ and CD8+ T cells. Objective: We aimed to compare the effect of bath PUVA and NB‐UVB clinically and on circulating T‐helper and T‐suppressor/cytotoxic cells in psoriasis. Patients and methods: Thirty‐four psoriatic patients divided into a bath PUVA‐treated group (18 patients) and a NB‐UVB‐treated group (16 patients) were compared regarding the disease severity by psoriasis area and severity index (PASI) score and percentage of circulating CD4+ and CD8+ T cells by flowcytometry before and after treatment. Results: After treatment, the bath PUVA group showed a significantly higher reduction of PASI score (85.44%) than the NB‐UVB group (58.72%). Mean peripheral CD4+ T‐cell percentage was significantly lower after [36.8; 95% confidence interval (CI) 33.80, 39.97] compared with before treatment (42.06; 95% CI 38.29, 45.83) (P<0.05) in the bath PUVA group while this difference was insignificant in the NB‐UVB group (P>0.05). Conclusion: Bath PUVA therapy is superior to NB‐UVB in the treatment of moderate and severe psoriasis with mild reversible side effects. Both modalities have a systemic effect decreasing peripheral CD4+ T cells, which is more with bath PUVA.     

CD26/dipeptidyl-peptidase IV in psoriatic skin: upregulation and topographical changes

Background Psoriasis is known to affect 2–3% of the population and can be considered an organ‐specific autoimmune disease. CD26/dipeptidyl‐peptidase IV (DPP‐IV) is a membrane‐bound protease with diverse properties. In theory, the expression of CD26/DPP‐IV has common grounds with three principal key players of the psoriatic pathogenesis: keratinocytes, T cells and cytokines. Objectives To assess CD26/DPP‐IV expression in psoriasis in order to expand on the search for complementary biomarkers related to inflammation and proliferation in psoriasis. Methods The pattern of expression of CD26/DPP‐IV was investigated on the mRNA‐, protein‐ and enzyme‐functionality level using immunohistochemical, immunofluorescent and enzyme activity labelling techniques. Results An 11‐fold significant increase of CD26/DPP‐IV on the mRNA level was demonstrated in psoriatic epidermal sheets compared with normal skin. Immunohistochemistry on psoriatic sections showed a distinct patchy honeycomb‐like CD26/DPP‐IV staining in the suprapapillary layers. Moreover, a clearly distinguishable column‐like staining pattern throughout the suprabasal compartment along the rete ridges was seen, whereas in normal skin these patterns were absent. Strikingly, CD26/DPP‐IV enzyme activity correlated with this immunohistochemical reactivity pattern for the CD26/DPP‐IV protein. The T‐cell bound expression of CD26/DPP‐IV in psoriatic skin was explicitly present, albeit in small quantities. Conclusions Our data provide clear evidence for a versatile upregulation of CD26/DPP‐IV expression in psoriatic (epi)dermis. Although the exact functional contribution remains speculative, the topographical distribution of this complex multifunctional protein suggests a suitable role as a complementary biomarker in psoriasis.     

A phase IIIb,multicentre, randomized,double‐blind,vehicle‐controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study

Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis. Objectives To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice. Methods A 16‐week, randomized, vehicle‐controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1–15) in addition to either topical C/B or drug‐free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16. Results A total of 730 patients received either ADA + C/B (n = 366) or ADA + vehicle (n = 364). PASI 75 response was initially higher with the combination therapy [14·8% for ADA + C/B vs. 5·8% for ADA + vehicle at week 2 (P < 0·001); and 40·7% vs. 32·4%, respectively, at week 4 (P = 0·021)]. After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64·8% for ADA + C/B vs. 70·9% for ADA monotherapy, P = 0·086). Safety findings were consistent with previous ADA trials. Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.     

Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman’s therapy

Goeckerman’s therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman’s therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. Forty otherwise healthy blood donors serve as a control group. The efficacy of GT was delineated by psoriasis area and severity index (PASI). The disease activity was significantly diminished by GT (P < 0.001). The serum levels of both VEGF and bFGF were statistically significantly correlated to PASI value in patients before the treatment by GT. The serum levels of VEGF (329.4 ± 125.5 pg/ml) and bFGF (10.2 ± 5.04 pg/ml) in patients before GT were significantly higher than those measured in healthy blood donors (VEGF 236.4 ± 55.9 pg/ml, bFGF 7.3 ± 3.7 pg/ml). The serum levels of both VEGF and bFGF were significantly diminished by GT. The level of VEGF dropped from 329.4 ± 125.5 pg/ml before GT to 278.5 ± 109.9 pg/ml after GT (P = 0.0042) and the level of bFGF fell from 10.2 ± 5.04 to 7.78 ± 4.5 pg/ml (P = 0.019). Comparing to healthy controls, the serum level of bFGF in psoriasis patients was normalised (P = 0.5723) after GT. In contrast, the serum level of VEGF remained significantly increased in psoriasis patients after GT in comparison with healthy blood donors (P = 0.0319). In conclusion, we found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.     

Serum adenosine deaminase levels in patients with psoriasis: a prospective case-control study

Adenosine deaminase (ADA) activity is a nonspecific marker of T cell activation. T cell activation is thought to play an important role in the pathogenesis of psoriasis. Our purpose was to assess the significance of serum ADA activity in psoriasis and its relevance to disease activity. ADA activity was determined with an enzymatic method in 25 patients with psoriasis and in 15 healthy subjects. These measurements were repeated for 10 patients after either PUVA or cyclosporin A treatments. Disease activity was estimated by the PASI scoring system. Serum ADA level was significantly elevated in patients with psoriasis compared to healthy subjects (p<0.05). There was a significant decrease in the ADA levels after treatment compared to pretreatment values in the same patients (p<0.05). There was no correlation between ADA levels and PASI scores.These results support the evidence that T cell activation is involved in the pathogenesis of psoriasis and that ADA may be valuable in the assessment of disease activity in psoriasis.     

Biologic therapies for psoriasis: practical experience in a U.K. tertiary referral centre

Summary Background Large‐scale clinical trials provide clear evidence of the efficacy and short‐term toxicity of biologic therapies for psoriasis. However, to date, there are few reports of the practical use of these therapies outside of the trial setting and, to our knowledge, none from a U.K. cohort of patients with psoriasis. Objectives (i) To assess efficacy and safety of efalizumab, etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21·8 and 21·7, respectively, outside of the clinical trial setting. (ii) To examine our approach to the processes involved in the initiation of biologic therapies in the era of National Institute for Health and Clinical Excellence guidance. Methods A retrospective case‐note review to identify all patients initiated on biologic therapies for psoriasis in a U.K. tertiary referral centre. Results At 3 months of treatment the efficacy of efalizumab (n = 28), etanercept (n = 70) and infliximab (n = 20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35% and 85%, respectively. All three biologics used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biologic therapy in 30% of cases. Streamlined approaches to screening and funding significantly (P ≤ 0·05) hastened the initiation of biologic therapies. Conclusions In a cohort of U.K. patients with severe psoriasis, biologic therapies have proved to be a significant step forward in expanding the therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long‐term safety of such drugs.     

A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment

Background Clinical studies of low‐dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects. Aim This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided‐dose schedule (three doses of MTX separated by 12‐h intervals once a week). Subjects and methods Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28–69 years) with moderate‐to‐severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9–42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration–time curve of plasma MTX in the interval 0–8 h post‐dose (AUC_0–8 h) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC_0–8 h of 1800 nmol·h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4‐week intervals. Results The AUC_0–8 h achieved 1360 ± 425 nmol·h/L (mean ± SD: range, 778–2400 nmol·h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5–22.5 mg). The mean (SD) steady‐state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1–174 nmol/L). The PASI decreased from 24·0 ± 8.0 (mean ± SD) at baseline to 8.0 ± 6.1 at day 110 (P < 0.001). Thirteen patients (87%) achieved a greater than 50% improvement in baseline PASI, and seven (47%) experienced a greater than 75% improvement. There was no relationship between the percent improvement from baseline PASI and the steady‐state concentration of MTXPGs in RBC. All patients tolerated MTX well. Throughout the study period, there was a continuous increasing trend in the geometric mean values of the mean corpuscular volume from 92.6 to 96.4 fL (P < 0.001) and of plasma homocysteine from 9.5 to 12.3 µmol/L (P < 0.005). The geometric mean serum alanine aminotransferase (ALT) activity slightly increased from 0.49 to 0.80 µkat/L (P < 0.05). However, only two patients had the ALT activity transiently elevated above twice the upper limit of normal. Conclusion Results of this pilot trial show that the steady‐state levels of MTXPGs in RBC vary less than threefold between patients and did not correlate with the change in PASI observed after 4 months of therapy with an individualised weekly dose of MTX. Whether pharmacokinetically guided dosing can improve the results of psoriasis therapy with MTX should be prospectively tested in large controlled studies.     

Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study. Objectives To assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. Methods Three hundred and fifty patients were enrolled in this phase III, 12‐week study (M10‐315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. The co ‐ primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results Of the briakinumab‐treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept‐treated patients and 4·2% of placebo‐treated patients (P < 0·001, for both comparisons). Of the briakinumab‐treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept‐treated and 6·9% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) briakinumab‐treated patients, one (0·7%) etanercept‐treated patient and two (2·8%) placebo‐treated patients. Conclusions In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.     

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index,severity and therapy

Background Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels. Objectives To understand the role/relationship of adipokines, as well as CRP, in a Portuguese psoriatic population, by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index (PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy. Methods A cross‐sectional (n = 66) and longitudinal study (before and after 12 weeks of therapy; n = 44) was performed; 10 patients started topical treatment, 17 narrow‐band ultraviolet B (NBUVB) and 17 psolaren associated with UVA (PUVA). Results Patients presented significantly higher BMI, leptin, resistin, TNF‐α, IL‐6 and CRP and significantly lower adiponectin values. CRP and IL‐6 correlated with PASI. Adiponectin and leptin were more altered in patients with higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After treatment, a significant reduction in PASI, CRP, resistin, TNF‐α and IL‐6, and a significant rise in adiponectin were observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical therapy was not associated with any significant change, except for TNF‐α. After NBUVB, a significant reduction was observed in TNF‐α and in CRP. For PUVA, we observed a significant reduction in TNF‐α, IL‐6 and CRP, and a significant increase in adiponectin. Conclusion In psoriatic patients, increased overweight/obesity was associated with raised leptin levels and decreased adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight/obese psoriatic patients. Resistin, IL‐6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL‐6, appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem to be more successful. Nonetheless, after NBUVB and PUVA, a low‐grade inflammation still persists.