Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta‐analysis of randomized controlled trials

Concerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I² statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.     

生物制剂治疗银屑病患者出现严重感染的风险评估:一项系统性回顾与荟萃分析

<正>肿瘤坏死因子抑制剂英夫利昔单抗、依那西普和阿达木单抗是目前用于治疗银屑病常用的3种生物制剂,新药优特克单抗是IL-12和IL-23拮抗剂,苏金单抗是IL-17受体拮抗剂。生物制剂通过抑制细胞因子,调控银屑病患者紊乱的免疫系统,从而发挥疗效。肿瘤坏死因子等细胞因子在细胞感染免疫应答和肉芽肿形成过程中是不可或缺的重要一员,因此生物治疗是否存在引起严重感染的风险     

Pediatric psoriasis: updates in biologic therapies

Psoriasis is not a rare disease in the pediatric population. Early recognition and treatment is necessary to improve the physical and psychological symptoms of psoriasis and minimize its adverse effects on future health. In moderate-to-severe cases, treatment is challenging. There is no Food and Drug Administration (FDA)-approved systemic treatment for children and adolescents with moderate-to-severe plaque-type psoriasis other than topical corticosteroids, and current treatment is limited to the ones that are used in adults, which may have more severe side effects in children. Recently, there have been advances in the use of biologic therapies, specifically tumor necrosis factor (TNF)-alpha blockers, for pediatric autoimmune diseases and pediatric psoriasis. The present review will summarize the data on TNF inhibitors for pediatric psoriasis, as well as detail studies that led to the approval of biologics in other pediatric autoimmune diseases.     

Risk of first-time and recurrent depression in patients with psoriasis: a population-based cohort study

Psoriasis is a common skin disease affecting approximately 5-10 percent of people in the Nordic countries, and more than 125 million people worldwide. The disease has been associated with low treatment adherence, meaning people don't stick with their treatment, and unhealthy lifestyle (e.g. smoking, alcohol consumption, decreased physical activity) and, in turn, cardiometabolic disease. Patients with psoriasis have a higher frequency of depression, but little is known about whether this is due to psoriasis itself, or whether this is predominantly due to patients’ comorbidities, meaning the diseases they suffer alongside their psoriasis. This study therefore examined the risk of depression in 247,755 patients with psoriasis compared with the general population. Using registry data from Denmark, this study found a slightly increased risk of developing depression in patients with psoriasis, independent of other risk factors such as comorbidity. Overall, the risk was modest, but a somewhat higher risk was seen in those people requiring a stronger type of treatment called biologic therapy, i.e. those with more severe psoriasis, and especially among patients aged 40 to 50 years. Notably, the highest occurrence of depression was among people with a prior history of depression, suggesting that these patients may represent a particularly vulnerable group in which increased awareness may be needed. Collectively, these results may help clinicians identify which patients are at particularly high risk of depression in whom pre-emptive measures may be needed to reduce the future risk of depression.     

Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study

This prospective long-term cohort study investigated the incidence of malignancies in severe psoriasis patients treated with cyclosporine. A total of 1252 patients were followed prospectively for up to 5 y. Malignancies were recorded prospectively. Incidence rates for malignancies were compared with the general population using standardized incidence ratios. The effect of duration of exposure to cyclosporine and to previously administered anti-psoriatic treatments on the incidence of malignancies was investigated using Poisson regression models. The mean age of patients was 43 y and on average, patients received cyclosporine for 1.9 y. Malignancies were diagnosed in 47 patients (3.8%), 49% of them had skin malignancies. The standardized incidence ratio in the study cohort was 2.1 as compared with the general population. The higher incidence of malignancies was attributed to a 6-fold higher incidence of skin malignancies, most of which were squamous cell carcinoma. The incidence of nonskin malignancy overall was not significantly higher in this study than in the general population. Duration of exposure to cyclosporine, exposure to psoralen and ultraviolet A, exposure to methotrexate, and exposure to immunosuppressants showed a significant effect on the incidence of nonmelanoma skin malignancies. In conclusion, treatment of psoriasis with cyclosporine is associated with an increased risk of nonmelanoma skin cancer. Patients treated for more than 2 y with cyclosporine were shown to have a higher risk. In addition, exposure to psoralen and ultraviolet A and to other immunosuppressants was shown to contribute to the overall risk.     

Efficacy of biologic therapies in psoriasis vulgaris

Psoriasis is a chronic, immune‐mediated skin disease that also has systemic manifestations. Biologic preparates: Adalimumab, Etanercept, and Infliximab are licensed for psoriasis vulgaris treatment in Albania. To compare the efficacy of biologic therapies used for psoriasis based in our experience. A cohort prospective study during the years 2016–2018 at UHC “Mother Teresa” Tirana. In the study took place 78 patient diagnosed with psoriasis and treated with biologic therapies. Psoriasis Area Severity Index (PASI) 50 and PASI 75 index were the parameters of response outcomes. PASI 50 was achieved for 6.8, 7.02, and 7.2 weeks in patients with Etanercept, Adalimumab, and Infliximab respectively and PASI 75 for 12.8, 11.4, and 11.42 weeks. X2 = 0.076, p > .05, nonsignificant difference. PASI 50 was achieved in 27.2% of subject treated with Etanercept, 67.4% Adalimumab, and 55.5% with Infliximab for the weeks mentioned above. Meanwhile PASI 75 was achieved in 45.4% of subject treated with Etanercept, 61.7% Adalimumab, and 25% with Infliximab. X2 = 15.28, p < .05, significant difference. Biologics have revolutionized the treatment of psoriasis. To select the most appropriate agent for patient, should be considered multiple factors including adverse effects, tolerance, patient preference, cost, and mode of administration.     

Risk of cancer in patients with psoriasis on biological therapies: a systematic review

Psoriasis is a skin condition that leads to inflammation, resulting in red, scaly skin. Biologic therapies are very powerful treatments for psoriasis, but unfortunately, they have significant effects on the immune system, which may increase the possibility of getting cancers. The authors of this study analysed previous research (until August 2016) that looked at whether patients with psoriasis who received biologic therapies got more cancers compared to other patients. Some studies found that there was an increase in certain types of skin cancers, called non‐melanoma skin cancers (NMSC). There was no increase in any other types of cancers in the studies. However, the authors recognised several weaknesses in the studies, which could have affected the results. More research is needed to know whether there really is an increased risk of skin cancer with biologic treatment. Patients participating in long term studies such as the British Association of Dermatologists Biologic Interventions Register (BADBIR) will help to answer this important question.