Psoriasis and bone mineral density: Implications for long‐term patients

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti‐psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty‐three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual‐energy X‐ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T‐score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.     

Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial

Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, selectively inhibits interleukin‐23, a key cytokine in the pathogenesis of psoriasis, by binding to its p19 subunit. In SustaIMM (ClinicalTrials.gov/NCT03000075), a phase 2/3, double‐blinded, placebo‐controlled study, Japanese patients with moderate to severe plaque psoriasis (n = 171) were stratified by bodyweight and concomitant psoriatic arthritis and randomized 2:2:1:1 to 75 mg risankizumab, 150 mg risankizumab, placebo with cross‐over to 75 mg risankizumab and placebo with cross‐over to 150 mg risankizumab. Dosing was at weeks 0, 4, 16, 28 and 40, with placebo cross‐over to risankizumab at week 16. The primary end‐point was 90% or more improvement from baseline in Psoriasis Area and Severity Index (PASI‐90) at week 16 for risankizumab versus placebo. Missing data were imputed as non‐response. All primary and psoriasis‐related secondary end‐points were met for both risankizumab doses (P < 0.001). At week 16, PASI‐90 responses were significantly higher in patients receiving 75 mg (76%) or 150 mg (75%) risankizumab versus placebo (2%). Corresponding response rates were 86%, 93% and 10% for static Physician Global Assessment (sPGA) score of clear/almost clear; 90%, 95% and 9% for PASI‐75; and 22%, 33% and 0% for PASI‐100, with significantly higher responses for both risankizumab doses versus placebo. Through week 52, PASI and sPGA responses increased or were maintained and treatment‐emergent adverse events were comparable across treatment groups. Both doses of risankizumab were superior to placebo in treating patients with moderate to severe plaque psoriasis. The safety profile was consistent with previous risankizumab trials, with no new or unexpected safety findings.     

Effective continuous systemic therapy of severe plaque‐type psoriasis is accompanied by amelioration of biomarkers of cardiovascular risk: results of a prospective longitudinal observational study

Background Severe psoriasis is associated with significant cardiovascular mortality. Objectives We investigated the effects of continuous systemic therapy on the cardiovascular risk of patients with severe plaque‐type psoriasis. Methods A total of 42 consecutive patients receiving systemic treatment for their severe plaque‐type psoriasis were included. The clinical course was monitored over 24 weeks. Initially as well as after 12 and 24 weeks, oral glucose tolerance tests were performed along with comprehensive laboratory monitoring. Results Responding patients, defined as a Psoriasis Area and Severity Index (PASI)‐50 response, showed correlations between the PASI and high‐sensitive C‐reactive protein (r = 0.45, P = 0.03) as well as with vascular endothelial growth factor (r = 0.76, P = 0.007). The adipokine resistin was positively and the potentially cardio‐protective adiponectin was negatively correlated with the PASI (r = 0.50, P = 0.02 and r = ?0.56, P = 0.007, respectively). Oral glucose tolerance tests yielded a correlation between the PASI and plasma levels for C‐peptide (r = 0.73, P = 0.02) at t = 120 min in patients with a pathological Homeostasis Model Assessment (>2.5), indicating that the state of peripheral insulin resistance is driven at least in part by the severity of the psoriatic inflammation. Correlations between the change of adipokine levels and change in PASI were more pronounced among patients with better clinical improvement (PASI‐75 vs. PASI‐50). Conclusions We document an amelioration of biomarkers of cardiovascular risk in patients with severe plaque‐type psoriasis responding to continuous systemic therapy. The impact on the patients’metabolic state was found to be better if the psoriatic inflammation was controlled for longer. Future studies need to compare the cardioprotective effects of different treatment modalities, based on hard clinical endpoints.     

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.     

Left ventricular systolic asynchrony: an important sign for cardiac involvement in plaque‐type psoriasis

Psoriasis is associated with cardiovascular diseases (CVD). The purpose of this study was to evaluate the relationship between Left Ventricular (LV) asynchrony and psoriasis. Asynchrony was assessed in 31 patients with psoriasis without evidence of CVD and 25 healthy subjects. All the patients and controls were subjected to tissue synchronization imaging (TSI), and conventional and tissue Doppler echocardiography. The time to regional peak systolic tissue velocity (Ts) in LV by the six‐basal‐six‐midsegmental model was measured on ejection phase TSI images, and four TSI parameters of systolic asynchrony were computed. C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in psoriatic patients were measured. All TSI parameters of LV asynchrony increased in psoriatic patients compared to the controls: the standard deviation (SD) of the 12 LV segments Ts (37.3 ± 14.8 vs. 24.6 ± 11.1, P = 0.002); the maximal difference in Ts between any two of the 12 LV segments (112.7 ± 39.8 vs. 83.1 ± 38.1, P = 0.01), the SD of the six basal LV segments (36.2 ± 17.3 vs. 23.2 ± 14.5, P = 0.008); and the maximal difference in Ts between any two of the six basal LV segments (91.3 ± 43.5 vs. 60.5 ± 37.3, P = 0.01). LV asynchrony was observed in 67.7% of psoriatic patients. Higher CRP (1.9 ± 1.3 vs. 0.92 ± 1.4, P = 0.04) and ESR (34.8 ± 17.3 vs. 20 ± 15.3, P = 0.03) levels were determined in patients with LV asynchrony. Regression analysis showed LV systolic asynchrony (P = 0.02), Tei index (P = 0.03), EF (P = 0.04), and E/A ratio (P = 0.04) were independently associated with psoriasis. LV asynchrony firstly described in patients with psoriasis may be an important finding of cardiac involvement in psoriasis.     

Prevalence and characteristics of metabolic syndrome in South‐East Asian psoriatic patients: A case–control study

The prevalence of metabolic syndrome in Asian psoriatic patients compared with that of the general population shows variable results. This study aimed to examine the association between psoriasis and metabolic syndrome in a Thai population. This case–control study included 199 psoriatic patients and 199 controls matched for sex and age from the general Thai population. There were 111 men (55.8%) and 88 women (44.2%) in both the psoriatic and control groups. The mean age (± standard deviation) of both groups was 50.04 ± 13.81 and 49.96 ± 14.39 years (P = 0.91), respectively. The majority of psoriatic cases (82.9%) were of plaque type. The prevalence of metabolic syndrome was significantly higher in psoriatic patients than in the general population at 49.25% versus 30.65%. After controlling for age, sex, smoking and alcohol drinking the odds ratio was 2.25 (P < 0.0001). The metabolic components which were significantly higher in the cases than controls included hyperglycemia, high blood pressure (HBP) and abdominal obesity. No statistically significant difference was found between the cases and controls regarding prevalence of obesity, hypertriglyceridemia and low high‐density lipoprotein cholesterol. Thai psoriatic patients had a higher prevalence of metabolic syndrome than the general population. In conclusion, the prevalence of HBP, hyperglycemia and abdominal obesity was significantly higher in cases than in controls.     

311 nm ultraviolet B-accelerated response of psoriatic lesions in adalimumab-treated patients

Background: Treatment with the tumor necrosis factor‐alpha antibody adalimumab for 12–16 weeks produces a satisfactory response [i.e., 75% reduction in psoriasis area and severity index (PASI)] in a majority (70–80%) of patients with psoriasis. We asked whether 311 nm ultraviolet B (UVB) can improve therapeutic response of psoriatic lesions to adalimumab. Methods: Four patients (age range, 49–67 years) with moderate to severe plaque‐type psoriasis were treated with standard dosage of adalimumab. During adalimumab therapy, a randomly selected body half (left or right, excluding the head) was irradiated with 311 nm UVB three times weekly for 6 weeks. Treatment response was monitored weekly in terms of half‐body PASI. Results: 311 nm UVB significantly accelerated the therapeutic response during adalimumab treatment. At the start of 311 nm UVB therapy, the mean PASI was 14.8. After 6 weeks of 311 nm UVB therapy, the mean PASI was 2.0 on UV‐irradiated body halves and 6.9 on non‐irradiated body halves (difference, 4.9; 95% confidence interval, 0.4–9.4; P=0.041; 2‐tailed paired t‐test). This corresponded to an overall mean PASI reduction from baseline (i.e., adalimumab start) of 86% on UV‐irradiated body halves vs. 53% on non‐irradiated body halves. Conclusion: 311 nm UVB may accelerate and improve the clearance of psoriatic lesions in adalimumab‐treated patients.     

Optical coherence tomography imaging of psoriasis vulgaris: correlation with histology and disease severity

Epidermal thickness (ET) has been suggested as a surrogate measure of psoriasis severity. Optical coherence tomography (OCT) is a recent imaging technology that provides real-time skin images to a depth of 1.8 mm with a micrometre resolution. OCT may provide an accurate in vivo measure of ET. It is, therefore, speculated that OCT may be used in the assessment of psoriasis vulgaris. A total of 23 patients with psoriasis vulgaris were systematically evaluated by OCT imaging and skin biopsy during treatment. Biopsies were graded for disease severity, and additional evaluation was done by the physician via psoriasis area and severity index (PASI) score, and by the patient through measures such as self-administered PASI, psoriasis life stress inventory index and dermatology life quality index. ET was calculated from OCT images. In comparison to normal skin, psoriasis appeared with a more irregular surface with a stronger entrance signal, a serrated dermo-epidermal junction was found and a less signal intensity in the dermis as shown in OCT images. ET measured in untreated plaques was thicker reflecting epidermal hyperproliferation and inflammation. The changes were significantly correlated with the biopsy grading (r ² = 0.41, p = 0.001) and ET significantly decreased with treatment (p = 0.0001). ET correlated significantly with self-reported measures of disease severity, but not with physician-assessed global PASI. The data suggest that OCT may be used to measure ET in psoriasis and the measurements correlate with several other parameters of disease severity. This implies that OCT assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions.     

Prolactin level is significantly elevated in lesional skin of patients with psoriasis

Background Accumulating data point to a potential role of prolactin in the pathogenesis of psoriasis. Methods We initiated a study including psoriasis patients (n = 15) and healthy volunteers (n = 15) as controls. Psoriasis area and severity index (PASI) score was evaluated, and prolactin levels in serum and blister fluid were assessed by enzyme‐linked immunosorbent assay (ELISA). Results Prolactin levels were significantly (P < 0.01) elevated in blister fluid of psoriatic lesional skin. Correlations between PASI score and different serum prolactin levels in lesional and non‐lesional skin were insignificant. Significant positive correlations of prolactin level were observed between lesional and non‐lesional skin in psoriasis (P < 0.05) and between serum and clinically normal skin in both psoriasis and control subjects (P < 0.05). Conclusions Locally produced prolactin may be involved in the pathogenesis of psoriatic lesions.     

Measurement of circulating miRNA-125a exhibits good value in the management of etanercept-treated psoriatic patients

This study aimed to explore the correlation of miR-125a with risk and severity of psoriasis, and further investigate the potential of miR-125a for predicting response to etanercept (ETN) treatment in psoriatic patients. Moderate to severe plaque psoriatic patients (n = 126) about to undergo ETN treatment for 6 months were recruited. Their plasma samples were obtained, and Psoriasis Area and Severity Index (PASI) scores and PASI-75 response rate were assessed at baseline (M0), and at 1 (M1), 3 (M3) and 6 months (M6) of treatment. Referring to PASI-75 response status at M6, patients were categorized as PASI-75 responders and PASI-75 non-responders. Healthy controls (HC, n =120) were also enrolled and their plasma samples were collected. In addition, plasma miR-125a was determined by quantitative polymerase chain reaction. miR-125a was decreased in psoriatic patients compared with HC; further, the receiver–operator curve (ROC) exhibited that miR-125a was of good value in differentiating psoriatic patients from HC with an area under the curve (AUC) of 0.802. In psoriatic patients, miR-125a was negatively associated with PASI score to some extent. Interestingly, baseline miR-125a was lower in PASI-75 responders than PASI-75 non-responders; further, ROC showed it predicted PASI-75 response at M6 to some extent with AUC of 0.672. Multivariate logistic regression also revealed that miR-125a was an independent predictive factor for worse PASI-75 response at M6. Furthermore, miR-125a expression was gradually increased during the treatment in PASI-75 responders, but unchanged in PASI-75 non-responders. Measurement of circulating miR-125a exhibits good value in the management of ETN-treated psoriatic patients.     

Psoriatic patients have a distinct structural and functional fecal microbiota compared with controls

Alterations in the gut microbiome have been implicated in the pathogenesis of several immune‐mediated inflammatory diseases such as psoriatic arthritis. This work aimed to characterize the gut microbial signature of patients with active psoriasis as compared with age‐, body mass index‐ and comorbidity‐matched non‐psoriatic controls and to correlate them with differential expression of metabolic pathways. Fecal samples were processed and 16S rRNA was sequenced. PICRUSt was used to perform an analysis of metabolic pathways. Of the 46 participants, 52% (n = 24) suffered from psoriasis. There was a significant difference in β‐diversity between the two groups. Psoriatic patients had a significant increase in the Firmicutes and Actinobacteria phyla as compared with matched controls. At the genus level, psoriatic patients had a unique bacterial composition. At the species level, the psoriatic patients showed significant increases in the relative proportions of (false discovery rate, <0.05) in Ruminoccocus gnavus, Dorea formicigenerans and Collinsella aerofaciens, while Prevotella copri and Parabacteroides distasonis were significantly decreased as compared with controls. PICRUSt analysis revealed increases in metabolic pathways related to lipopolysaccharide function in the psoriatic cohort. These data demonstrate unique fecal microbial and metabolic signatures in psoriatic patients.     

Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.     

Heredity of acne in Korean patients

Acne is a chronic inflammatory disease of the pilocebaceous unit that presents with various spectrum and severity. Genetic backgrounds and environmental factors are also considered to be relevant, but few studies have focused on Korean patients. A cross‐sectional epidemiologic study on family history of Korean acne patients was performed to analyze family history of acne, and to compare the severity and characteristics of acne in association with family history. A total of 221 patients were enrolled, 98 male (44.3%) and 123 female (55.7%). Patients were grouped as patients with (A+) or without (A‐) family history of acne. In a second analysis, patients with any experience of acne treatment were evaluated. Severity of acne was measured with Burton's grading system and Korean Acne Grading System (KAGS). Female patients had a higher tendency to have family history than males (P = 0.002). Group A+ had statistically significant earlier onset of acne (P = 0.002). In inexperienced patients, patients with family history showed a relatively earlier onset (P = 0.084). This study confirmed the role of heredity in acne. Family history of acne is associated with earlier onset of the disease, and more non‐inflammatory lesions.     

The relationship between oxidative stress,smoking and the clinical severity of psoriasis

Background Recent studies suggested that increased oxidant products and decreased antioxidant system functions may be involved in the pathogenesis of psoriasis. In this study, we investigated total oxidative status, Paraoxonase (PON)1/arylesterase enzyme activities and severity of the disease in smoker and non‐smoker psoriatic patients. Methods Fifty‐four patients with plaque type psoriasis (28 smokers and 26 non‐smokers) and 62 healthy volunteers (16 smokers and 46 non‐smokers) were enrolled in the study. Serum total oxidant status (TOS), total antioxidant capacity (TAC) and arylesterase levels were measured, and oxidative stress index (OSI) was calculated in all participants. Results Psoriasis Area and Severity Index scores were significantly higher in smoker patients than in non‐smoker patients (P = 0.014). Both smoker and non‐smoker patients had significantly increased TOS levels and OSI values and decreased TAC levels than healthy subjects (all P values = 0.000). The TAC and TOS levels, OSI values and arylesterase activities were similar between smoker and non‐smoker patients. The levels of triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) were not significantly different between smoker and non‐smoker psoriasis patients. When compared with non‐smoking controls, only smoking psoriasis patients had significantly higher TG (P = 0.005), lower HDL (P = 0.022) and lower arylesterase levels (P = 0.015). There were no significant correlations with Psoriasis Area and Severity Index (PASI) scores and TAC, TOS, OSI, TG, TC, HDL and LDL levels in all psoriasis patients. Conclusions Oxidative stress is increased in psoriasis patients regardless of their smoking status. The decreased arylesterase activity in smoker psoriasis patients suggested that smoking may be a considerable risk factor that increases the severity of psoriasis by increasing oxidative stress in these patients.     

Red blood cell distribution width is increased in patients with psoriasis vulgaris: A retrospective study on 261 patients

Circulating inflammatory cytokines and markers are increased in patients with psoriasis. Recent studies have shown that a higher red blood cell distribution width (RDW) is associated with disease activity in various disorders. Our objective was to investigate whether RDW is increased in psoriasis patients, and to evaluate its possible association with disease severity. We conducted a retrospective study of psoriasis patients seen in a university hospital in South Korea. Information about demographics, hematological parameters and disease severity were collected. Statistical analysis was performed using Student's t‐test, multivariable logistic regression, Fisher's exact test and Spearman's rank correlation coefficient analysis as appropriate. A total of 261 psoriasis patients and 102 healthy controls were included in our study. The mean RDW value was significantly increased in psoriasis patients compared with healthy control (P = 0.037). Compared with mild psoriasis patients (Psoriasis Area and Severity Index [PASI], <7), moderate to severe patients (PASI, ≥7) showed significantly higher RDW values (P = 0.044). However, RDW did not show significant correlation with PASI (P = 0.358). When patients were divided into two groups according to their RDW value (<14.6% and ≥14.6%), the mean value of PASI was not significantly different (P = 0.219). Patients with psoriasis showed increased RDW values compared with healthy controls. It was also higher in the moderate and severe disease group than the mild group. Though this is only a pilot study, it is possible that RDW value can reflect the inflammatory status of psoriasis patients.     

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis

To discover novel biomarkers of psoriasis, a target‐specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR‐3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR‐3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR‐3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR‐3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR‐3 levels were significantly elevated in psoriatic arthritis compared to non‐psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR‐3 could reflect disease progression in psoriasis. Collectively, serum VEGFR‐3 may have a clinical value in monitoring disease activity of psoriasis.     

Secukinumab efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis: Subanalysis from ERASURE,a randomized,placebo‐controlled,phase 3 study

Secukinumab, a fully human anti‐IL‐17A monoclonal antibody, neutralizes IL‐17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate‐to‐severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52‐week, double‐blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI‐111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co‐primary endpoints (Week 12) were ≥75% improvement in psoriasis area‐and‐severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5‐point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12‐week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate‐to‐severe plaque psoriasis in the Japanese patients.     

Elevated serum levels of interleukin 21 are associated with disease severity in patients with psoriasis

Background  Psoriasis is an immune disorder involving numerous cytokines. Recent studies have shown that interleukin (IL)‐21 plays an important role in a variety of inflammatory and autoimmune diseases. It is highly expressed in psoriatic plaques and promotes the proliferation of epidermis in mice. It seems that IL‐21 plays an important role in the pathogenesis of psoriasis. However, whether or not it is elevated in the peripheral blood of patients with psoriasis and is associated with disease severity is unclear. Therefore, our study focuses on serum IL‐21 levels and their correlation with disease severity. Objectives  To detect serum IL‐21 levels in patients with psoriasis and investigate the correlation between these and the Psoriasis Area and Severity Index (PASI) scores. Methods  Blood samples were collected from patients with plaque psoriasis and from healthy control subjects. Serum IL‐21 levels were measured by enzyme‐linked immunosorbent assay in 37 patients with psoriasis and 37 healthy controls. The PASI scores of patients with psoriasis and their correlation with serum IL‐21 levels were evaluated. Results  Serum IL‐21 levels were higher in patients with psoriasis than in healthy controls (P < 0·01). Serum IL‐21 levels were positively correlated with PASI scores in the patients with psoriasis (r = 0·471, P < 0·01). Conclusions  Serum IL‐21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. These results indicate that IL‐21 may play an important role in the pathogenesis of psoriasis.     

Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: Subgroup analysis from the CLEAR study

The 52‐week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient‐reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double‐blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.     

Are all patients with psoriasis at increased risk for coronary artery disease?

Associations have been recently recognized between psoriasis and an increased incidence of atherosclerotic diseases. However, there are scarce data on the prevalence of coronary lesions in patients with psoriasis. The aim of this study was to identify the calcified and non‐calcified atherosclerotic coronary lesions in patients with psoriasis compared to controls. Forty patients with psoriasis and 42 control subjects matched for age, sex, and cardiovascular risk profile were included in this case–control study. Coronary lesions were evaluated by a 128‐slice dual source multidetector computed tomography scanner. Coronary calcification scoring was calculated according to the Agatston score. The prevalence of atherosclerotic coronary lesions (psoriasis: 15%, controls: 16.7%; P = 0.83) and the mean coronary calcification scoring (psoriasis: 9.9 ± 35.2 Agatston unit, controls 2.8 ± 12.0 Agatston unit; P = 0.81) did not show a significant difference between the two groups. Multivariate analysis identified age ≥48 years and fasting blood glucose ≥99.0 mg/dl as independent predictors of coronary artery disease in patients with psoriasis (F = 30.9; P = 0.001; adjusted R² = 0.49). Patients with psoriasis had the same prevalence of calcified and non‐calcified atherosclerotic coronary lesions as compared to controls. Our results demonstrated the necessity of considering the age and fasting blood glucose of patients with psoriasis in a decision for further cardiovascular evaluation.