Risankizumab vs. ustekinumab for plaque psoriasis: a critical appraisal

Psoriasis is a skin condition that causes a scaly, red rash which can vary from affecting only small areas of the body, such as the elbows and knees, to affecting a larger area of the body. It affects approximately 2% of people in the U.K. There are many treatments for psoriasis, including creams, tablets and injections. The injections are known as biologics and these target specific parts of the immune system that can be very active in psoriasis. The authors of this paper, based in the U.K., aimed to assess the quality of two trials (called UltIMMa-1 and UltIMMa-2) that compared two of these biologics, risankizumab and ustekinumab. These trials included patients from 14 countries, and showed that risankzizumab is more effective than ustekinumab for treating patients with moderate or severe psoriasis. The authors found that these trials were well-conducted because they recruited a large number of patients and the methods used were sound and clearly reported. They analysed the data in a way which is conservative and doesn't over-estimate the effect of the new treatment, risankizumab. One criticism of the trials is that it could be difficult to apply the results to some groups of patients in the clinical setting (i.e. in real life treatment rather than in a trial). For example, it's not clear whether patients who have failed tablet or some other injection treatments would respond differently from those who have never had such treatments. Additionally, some patients with other illnesses were excluded from the study, though it was not specified which illnesses lead to exclusion. The authors conclude that this study does clearly demonstrate that risankizumab is more effective than ustekinumab, though more work needs to be done to identify why this is the case.     

The association between psoriasis and health-related quality of life,work productivity,and healthcare resource use in Brazil

Background:Psoriasis is a chronic, immune mediated inflammatory condition that affects a significant amount of the global population. Yet geographic variability in the consequences of psoriasis warrants region-level analyses.Objectives:The current study contributes to the psoriasis outcomes literature by offering a comprehensive assessment of the humanistic and economic burden in Brazil.Methods:The 2012 Brazil National Health and Wellness Survey (N=12,000) was used to assess health-related quality of life (Short Form-12, version 2), work productivity, and healthcare resource use associated with experiencing psoriasis vs. no psoriasis, along with varying levels of psoriasis severity.Results:A total of 210 respondents reported diagnosis of psoriasis (N=157, 42, and 11 reporting mild, moderate, and severe psoriasis, respectively). Compared with controls, respondents with psoriasis reported diminished mental component summary scores and health utilities, as well as increased presenteeism, activity impairment, and physician visits over the past six months, adjusting for covariates. Among those with psoriasis, physical health decreased as psoriasis severity increased. Although work productivity and healthcare resource utilization did not differ with psoriasis severity, the high rates of productivity loss (e.g. 45.5% presenteeism in the severe psoriasis group) suggest an economic burden.Study limitations:Cost analyses were not performed, and cross-sectional patient-reported data limit causal conclusions and may reflect reporting biases.Conclusions:Nevertheless, these results suggest a significant burden to patients with psoriasis across both humanistic and economic outcomes. The association between psoriasis and mental health aspects and health utilities were particularly strong and exceeded what would be considered clinically meaningful.     

Positive treatment effects of ustekinumab in psoriasis: Analysis of lesional and systemic parameters

Ustekinumab, a human anti‐interleukin (IL)‐12/IL‐23p40 monoclonal antibody has demonstrated significant efficacy in patients with moderate‐to‐severe psoriasis. Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and ex vivo T‐helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were evaluated at baseline and week 12. Inflammatory serum protein levels were measured at baseline, week 2 and week 12. At week 12, median epidermal thickness decreased from 312.1 to 132.7 μm, and median levels of cellular proliferation (Ki67) and T‐cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively, in the combined ustekinumab group (all P ≤ 0.002). Serum levels of tumor necrosis factor (TNF)‐α, C‐C motif ligand 27 (CCL27) and other inflammatory cytokines remained unchanged. Minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab treatment, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leukocyte antigen‐DR (HLA‐DR), and C‐X‐C motif receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to external stimuli in PBMC was observed following placebo or ustekinumab treatment. Ustekinumab improves histological psoriasis measures, with minimal impact on the systemic immune system.     

Inflammatory arthritis following ustekinumab treatment for psoriasis: a report of two cases

Psoriasis is a chronic inflammatory skin condition, characterized by T‐helper (Th) 1 and Th17 cell activation. Ustekinumab is a fully human immunoglobulin G1κ monoclonal antibody that targets the common p40 subunit that is shared by both interleukin (IL)‐12 and IL‐23, consequently inhibiting T‐cell differentiation along both Th1 and Th17 pathways. This is a report of two patients who developed psoriatic arthritis during ustekinumab treatment for psoriasis. Neither patient had a personal or family history of arthritis.     

Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial

BACKGROUND: When this study was initiated, no previous studies comparing methotrexate and ciclosporin for moderate to severe plaque psoriasis had been performed. OBJECTIVES: To compare the effectiveness, quality of life and side-effects of methotrexate and ciclosporin treatments in a context reflecting normal clinical practice. METHODS: Eighty-four patients with moderate to severe plaque psoriasis were randomized to treatment with methotrexate or ciclosporin for 12 weeks. The primary outcome was the Psoriasis Area and Severity Index (PASI). The secondary outcome was quality of life, measured by the Dermatology Life Quality Index (DLQI) and the 36-item Short Form Health Survey (SF-36). A visual analogue scale (VAS) was used for patients' assessment. RESULTS: Sixty-eight patients started treatment and were included in the analysis. Dropout before initiation of treatment was higher in the ciclosporin group. Mean PASI change from baseline at 12 weeks was 58% in the methotrexate group and 72% in the ciclosporin group, showing ciclosporin to be more effective than methotrexate. Improvement of the VAS score was higher in the ciclosporin group. The methotrexate group showed a greater improvement in the subscale Physical Functioning of the SF-36. No significant difference between the groups was found for DLQI. CONCLUSIONS: Treatment with methotrexate or ciclosporin for chronic plaque psoriasis brings satisfactory disease control, improved quality of life and tolerable side-effects. A statistically significant difference in effectiveness between treatment groups was recorded, showing ciclosporin to be more effective than methotrexate in a short-term perspective.     

Nemolizumab in moderate to severe atopic dermatitis: An exploratory analysis of work productivity and activity impairment in a randomized phase II study

Atopic dermatitis negatively impacts work productivity. This study investigated the impact of nemolizumab on work productivity and activity impairment in adults with moderate to severe atopic dermatitis inadequately controlled by topical treatments in a two‐part, phase II, randomized control trial. The Work Productivity and Activity Impairment – Atopic Dermatitis questionnaire was an exploratory end‐point. Part A was a 12‐week, placebo‐controlled study in which patients received s.c. nemolizumab 0.1, 0.5 or 2.0 mg/kg every 4 weeks or 2.0 mg/kg every 8 weeks. Part B was a 52‐week extension in which all patients received active treatment. A total of 138 patients had Work Productivity and Activity Impairment – Atopic Dermatitis data; 104 were employed at baseline. At week 12, patients receiving nemolizumab every 4 weeks showed greater mean (standard error) Work Productivity and Activity Impairment – Atopic Dermatitis improvement (score reduction) from baseline versus placebo: Percent Work Time Missed (0.1, 0.5 or 2.0 mg/kg vs placebo): –4.0% (3.9%), –1.7% (4.2%) and –1.6% (4.2%) versus 4.9% (4.5%); Percent Impairment While Working, –15.8% (6.0%), –24.1% (6.5%) and –34.3% (6.4%) versus –16.5% (7.1%); Percent Overall Work Impairment, –16.3% (6.0%), –23.1% (6.5%) and –34.5% (6.3%) versus –16.6% (7.1%); and Percent Activity Impairment, –13.4% (5.3%), –23.5% (5.3%) and –41.9% (5.5%) versus –10.9% (5.7%). Improvements were sustained through week 64. Nemolizumab‐treated patients with moderate to severe atopic dermatitis reported improvements in Work Productivity and Activity Impairment through week 64.     

Secukinumab治疗成人中重度银屑病疗效和安全性的Meta分析

目的:评价Secukinumab治疗成人中重度银屑病的疗效和安全性。方法:计算机检索PubMed、EMBASE、Cochrane图书馆、中国知网、维普期刊数据库、万方医学数据库、中国生物医学文献数据库有关Secukinumab治疗成人中重度银屑病的随机对照试验文献,时间为数据库建库时间至2017年2月,由两名独立的研究员对纳入的文献进行质量评价,用RevMan 5.3软件进行Meta分析。结果:分析共纳入7篇文献、3474例成人中重度银屑病患者。Meta分析结果显示,300 mg Secukinumab治疗组中PASI积分下降75%、90%和100%的患者例数和研究者全面评估(IGA)分数为0或1的患者例数高于150 mg Secukinumab治疗组及安慰剂组,差异均有统计学意义(P0.00001)。300 mg和150 mg Secukinumab治疗组中患者不良反应发生率明显高于安慰剂组,但300 mg Secukinumab治疗组和150mg Secukinumab治疗组间不良反应发生率差异无统计学意义。结论:300 mg Secukinumab治疗中重度银屑病疗效明显优于150 mg Secukinumab,不良反应发生率无明显差异。     

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.     

Measures of clinical severity, quality of life, and psychological distress in patients with psoriasis: a cluster analysis

The impact of psoriasis on patients' quality of life may be quite destructive, and measures of disease status alone seem to have questionable validity in describing the true burden of illness. Our aim was to study, in patients with psoriasis, the relationship between classical measures of clinical status (i.e., PASI and SAPASI) and quality-of-life indexes (i.e., Skindex-29, Dermatology Life Quality Index, Psoriasis Disability Index, Impact of Psoriasis Questionnaire). In addition, two psychological distress indexes (i.e., Psoriasis Life Stress Inventory, 12-item General Health Questionnaire) were assessed. Data were collected between February 2000 and July 2001 at the inpatient wards of the Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large project on clinical, epidemiologic, emotional, and quality-of-life aspects of psoriasis. A cluster analysis of all the above-mentioned instruments was conducted on 786 eligible patients hospitalized with a diagnosis of psoriasis. Correlations between instruments were also analyzed in subsets of patients based on the main variables of interest. The instruments clustered in two distinct groups, one formed by clinical severity measurements and the other grouping all the quality-of-life and psychological indexes. The correlations between instruments observed in the subgroups determined by different sociodemographic and clinical variables showed the same pattern. In conclusion, the dissimilarity between clinical severity assessment and patient-centered measures stresses the need for a more comprehensive assessment of severity of psoriasis.