Psoriasis is a systemic, immune‐mediated disorder, characterized by inflammatory skin and joint manifestations. A range of co‐morbidities is associated with psoriasis, including metabolic diseases, ...such as diabetes, and psychological disorders. Although the systemic nature of psoriasis often remains unrecognized, the inflammatory processes involved may be associated with the development of co‐morbidities, which, themselves, have a significant impact on the patient's health and quality of life. The relative risks of myocardial infarction (MI) and stroke are increased in patients with psoriasis compared with the general population. These are especially seen in younger patients with more severe disease, and are believed to contribute to the 3‐ to 4‐year reduction in life expectancy among patients with severe psoriasis. The recent results of large studies indicate that the increased cardiovascular (CV) risk is at least partially attributable to psoriasis and independent of the presence of metabolic co‐morbidities. The possible interplay between psoriasis and CV disease is complex. Metabolic diseases such as obesity and diabetes have overlapping genetic predispositions with psoriasis. Both conditions are likely to also interact at a functional level because obesity and the up‐regulation of pro‐inflammatory mediators in psoriasis appear to influence adipocyte homoeostasis, inducing non‐professional immune functions. This may perpetuate psoriatic inflammation, displaying similarities to the immunopathogenesis of atherosclerosis. Finally, the disturbed adipokine profile and inflammation associated with psoriasis enhances insulin resistance, causing subsequent endothelial dysfunction, atherosclerosis and eventual coronary events. The differential contribution of psoriasis and uncontrolled classical CV risk factors to the increased CV risk seen in psoriasis patients is not clear. Successful treatment with methotrexate appears to lower the rates of MI in patients with psoriasis. Tumour necrosis factor‐α (TNF‐α) inhibitors are known to counteract insulin resistance and emerging studies demonstrate an even higher protective effect of TNF‐α antagonist therapy against the development of diabetes or CV co‐morbidities in patients. The recent data reviewed here indicate a role for earlier and more appropriate treatment of psoriasis with drugs such as TNF‐α antagonists. Such an approach has the potential to significantly improve patient outcomes through the treatment of psoriasis itself and possibly also in protection against co‐morbidities.
Mental health is an important component of public health, especially in times of crisis. However, monitoring public mental health is difficult because data are often patchy and low-frequency
. Here ...we complement established approaches by using data from helplines, which offer a real-time measure of 'revealed' distress and mental health concerns across a range of topics
. We collected data on 8 million calls from 19 countries, focusing on the COVID-19 crisis. Call volumes peaked six weeks after the initial outbreak, at 35% above pre-pandemic levels. The increase was driven mainly by fear (including fear of infection), loneliness and, later in the pandemic, concerns about physical health. Relationship issues, economic problems, violence and suicidal ideation, however, were less prevalent than before the pandemic. This pattern was apparent both during the first wave and during subsequent COVID-19 waves. Issues linked directly to the pandemic therefore seem to have replaced rather than exacerbated underlying anxieties. Conditional on infection rates, suicide-related calls increased when containment policies became more stringent and decreased when income support was extended. This implies that financial relief can allay the distress triggered by lockdown measures and illustrates the insights that can be gleaned from the statistical analysis of helpline data.
Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic ...therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established. Implementation of treatment goals in the daily management of psoriasis will improve patient care and mitigate the problem of undertreatment. It is planned to evaluate the implementation of these treatment goals in a subsequent programme involving patients and physicians.
Psoriasis is a chronic inflammatory skin condition that affects approximately 2% of the population. Up to 50% of patients with psoriasis have concurrent nail psoriasis, with a lifetime incidence of ...80% to 90%. Up to 30% of patients with skin psoriasis also have psoriatic arthritis (PsA) and of these, approximately 80% have nail disease. However, nail involvement is often overlooked by physicians, despite the significant burden it places on patients as a result of functional impairment of manual dexterity, pain and psychological stress. Affected nail plates often thicken and crumble, and because they are very visible, patients are usually concerned about the appearance of their nails, often causing them to avoid normal day‐to‐day activities (including work). In the longer‐term, nail involvement may be a signal of a more severe form of psoriasis or a precursor of PsA. Conventional treatment of nail psoriasis is generally considered inconvenient by patients, and it is limited by adverse effects and often a reduction in efficacy over time. There is also a lack of controlled clinical trials’ data and no consistent treatment approach has been advocated. Recently, the effects of biologic agents targeted against tumour necrosis factor alpha (TNFα) on nail psoriasis have been investigated. The multicentre, double‐blind EXPRESS European Infliximab for Psoriasis (Remicade) Efficacy and Safety Study trial revealed that infliximab 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks significantly improved nail psoriasis, evaluated using the Nail Psoriasis Severity Index (NAPSI) in 378 patients with moderate to severe psoriasis. Significant improvement was reported as early as week 10, and at week 50 full nail clearance was evident in 45% of patients receiving infliximab. There is also evidence from small studies that infliximab significantly improves nail lesions and quality of life in patients with nail psoriasis. There is a need for improving the awareness of nail psoriasis and its impact on patients’ quality of life. Moreover, the potential role for nail involvement as a link between psoriasis and PsA underlines its importance and the need for effective management. Infliximab has been shown to improve psoriatic nail lesions and quality of life, and it should be considered as one of the most appropriate available treatment options for the many patients with this distressing condition.
Conflicts of interest
None declared.
Article Note: Funding sources: the study was funded by Medac, Wedel, Germany. Medac had no role in the study design, data collection, data analysis, manuscript preparation or publication decisions. ...Conflicts of interest: K.R. has served as an advisor and/or paid speaker for and/or has participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Covagen, Dermira, Forward Pharma, Fresenius Medical Care, Galapagos, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB, Valeant and Xenoport. M.A. has served as an advisor and/or paid speaker for and/or has participated in clinical trials sponsored by Abbott/AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma, GSK, Hexal, Janssen-Cilag, LEO Pharma, Medac, MSD, Novartis, Pfizer, Sandoz, Teva, TK, Trevi, UCB and Xenoport. Byline: K. Reich, C. Sorbe, L. Griese, J.L.K. Reich, M. Augustin
Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe ...psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS).
The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab.
A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs.
Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.
Summary
Background
Tildrakizumab is a high‐affinity, humanized, IgG1/κ, anti‐interleukin (IL)‐23p19 monoclonal antibody that does not bind human IL‐12 or p40 is being developed for the treatment of ...chronic plaque psoriasis.
Objectives
To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate‐to‐severe chronic plaque psoriasis.
Methods
A three‐part, randomized, double‐blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, 200 mg) or placebo at weeks 0 and 4 (part I) and every 12 weeks thereafter until week 52 (part II). Study drug was discontinued at week 52 and participants were followed through week 72 (part III). Primary efficacy end point was Psoriasis Area and Severity Index (PASI) 75 response at week 16. Adverse events (AEs) and vital signs were monitored throughout the study.
Results
At week 16, PASI 75 responses were 33·3% (n = 14), 64·4% (n = 58), 66·3% (n = 59), 74·4% (n = 64) and 4·4% (n = 2) in the 5‐, 25‐, 100‐ and 200‐mg tildrakizumab and placebo groups, respectively (P ≤ 0·001 for each tildrakizumab dose vs. placebo). PASI 75 response was generally maintained through week 52; only eight of 222 participants who achieved PASI 75 response at week 52 and continued to part III relapsed following discontinuation up to week 72. Possible drug‐related serious AEs included bacterial arthritis and lymphoedema (part I), and melanoma, stroke, epiglottitis and knee infection (part II).
Conclusions
Tildrakizumab had treatment effects that were superior to placebo, maintained for 52 weeks of treatment, and persisted for 20 weeks after cessation. Tildrakizumab was generally safe and well tolerated. These results suggest that IL‐23p19 is a key target for suppressing psoriasis.
What's already known about this topic?
Immune mechanism‐specific targeted biological treatments have successfully demonstrated improvements in clinical outcomes in patients with chronic plaque psoriasis.
Selective interleukin (IL)‐23 inhibition has been a recent target for novel therapies and small initial phase I trials have confirmed safety and preliminary efficacy in humans.
What does this study add?
This is the first large‐scale phase II trial to evaluate a monoclonal antibody that selectively inhibits IL‐23 in patients with chronic plaque psoriasis
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Linked Comment: Strober, Br J Dermatol 2015; 173: 887–888.
To fully deploy the potential of semiconductor nanocrystal films as low-cost electronic materials, a better understanding of the amount of dopants required to make their conductivity metallic is ...needed. In bulk semiconductors, the critical concentration of electrons at the metal-insulator transition is described by the Mott criterion. Here, we theoretically derive the critical concentration nc for films of heavily doped nanocrystals devoid of ligands at their surface and in direct contact with each other. In the accompanying experiments, we investigate the conduction mechanism in films of phosphorus-doped, ligand-free silicon nanocrystals. At the largest electron concentration achieved in our samples, which is half the predicted nc, we find that the localization length of hopping electrons is close to three times the nanocrystals diameter, indicating that the film approaches the metal-insulator transition.
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