Ustekinumab: a review of its use in the management of moderate to severe plaque psoriasis

Ustekinumab (Stelara?) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to or are intolerant of other systemic therapies or phototherapy. This article reviews the efficacy and tolerability of ustekinumab in patients with moderate to severe plaque psoriasis, as well as summarizing its pharmacological properties. Ustekinumab attenuates the immune cell activation properties of IL-12 and IL-23. It interrupts the abnormal activation of signalling and cytokine cascades that underlie the pathology of psoriasis by reducing the expression of IL-12- and IL-23-induced cell surface markers that mediate skin homing, activation and cytokine release. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90?mg provided a rapid and durable improvement in psoriasis area severity index (PASI) scores for patients with moderate to severe plaque psoriasis. A significantly greater proportion of patients receiving ustekinuman 45 or 90?mg compared with those receiving placebo achieved a ≥75% improvement from baseline in PASI score following 12 weeks' treatment (primary endpoint). Improvements in PASI scores were evident following 2 weeks' treatment with ustekinumab and were sustained for up to 3 years. Treatment with ustekinumab 45 or 90?mg also improved health-related quality-of-life scores from baseline. Following 12 weeks' treatment, ustekinumab 45 or 90?mg was more effective than etanercept 50?mg twice weekly in providing symptomatic relief for patients with moderate to severe plaque psoriasis. Furthermore, ustekinumab treatment provided effective symptomatic improvement for almost half of the patients who showed no response to 12 weeks' treatment with etanercept. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. In conclusion, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.     

Ustekinumab: a review in the treatment of plaque psoriasis and psoriatic arthritis

Psoriasis is a complex, multigenic immune/inflammatory-mediated disorder that variably affects the skin, nails, and joints. In September 2009, ustekinumab (Stelara?), a monoclonal antibody that targets interleukin 12 (IL-12) and 23 (IL-23), was approved in the United States for treatment of moderate-to-severe plaque psoriasis. The drug's mechanism of action is derived from extensive immunologic and genomic research identifying IL-12 and IL-23 of the Th1 and Th17 inflammatory pathways, respectively, as key mediators of psoriasis. Ustekinumab is a completely human monoclonal antibody to the shared p40 subunit of IL-12 and IL-23. The drug has demonstrated efficacy, short-term safety, and convenience of use in the treatment of plaque psoriasis and psoriatic arthritis. Though long-term safety concerns remain, ustekinumab adds to the current treatment armamentarium and holds promise to improve quality of life. This is a concise and current review of ustekinumab in the treatment of plaque psoriasis and psoriatic arthritis, with focus on data from the seven published clinical trials.     

Puerto Rico psoriasis study group: efficacy and safety of etanercept

BACKGROUND:Although major advances in the understanding of its pathogenesis have been achieved, psoriasis remains an incurable disease. In April 2004, etanercept, an antagonist of TNF-alpha, was approved by the Food and Drug Administration for the treatment of chronic, moderate to severe plaque psoriasis in adults. In this study we intend to document the efficacy and further establish the safety profile of etanercept for the treatment of moderate to severe psoriasis in our population and compare our data to the Leonardi et al study published in 2003. METHODS: A total of 26 patients were followed for a period of 24 weeks. Subjects were administered 25 mg of etanercept subcutaneously twice weekly for 24 weeks. Patients were seen every 4 weeks to measure clinical improvement by means of the psoriasis area and severity index (PASI) scores. Development of side effects was also assessed. RESULTS: Ninety-two percent of the patients had an improvement of greater than 50% in their PASI score, with 79% of these patients with a PASI improvement of 75% or greater. Adverse events were uncommon and none required the permanent discontinuation of treatment. CONCLUSION: Treatment with etanercept was well-tolerated and resulted in significant sustained improvement of psoriasis throughout a period of 24 weeks. Our data strongly correlates with the findings reported by Leonardi et al in 2003.     

Informative dropout modeling of longitudinal ordered categorical data and model validation: application to exposure–response modeling of physician’s global assessment score for ustekinumab in patients with psoriasis

The physician’s global assessment (PGA) score is a 6-point measure of psoriasis severity that is widely used in clinical trials to assess response to psoriasis treatment. The objective of this study was to perform exposure–response modeling using the PGA score as a pharmacodynamic endpoint following treatment with ustekinumab in patients with moderate-to-severe psoriasis who participated in two Phase 3 studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 or 90 mg or placebo, followed by active treatment or placebo crossover to ustekinumab, dose intensification or randomized withdrawal and long-term extension periods. A novel joint longitudinal-dropout model was developed from serum ustekinumab concentrations, PGA scores, and patient dropout information. The exposure–response component employed a semi-mechanistic drug model, integrated with disease progression and placebo effect under the mixed-effect logistic regression framework. This allowed potential tolerance to be investigated with a mechanistic approach. The dropout component of the joint model allowed the examination of its potential influence on the exposure–response relationship. The flexible Weibull dropout hazard function was used. Visual predictive check of the joint longitudinal-dropout model required special handling, and a conditional approach was proposed. The conditional approach was extended to external model validation. Finally, appropriate interpretation of model validation is discussed. This longitudinal-dropout model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate-to-severe plaque psoriasis.     

Efalizumab

INTRODUCTION: Conventional systemic therapies for psoriasis are associated with serious toxicities that can limit long-term use. In recent years, biological therapies have offered the possibility of long-term therapy with improved safety and efficacy for the treatment of psoriasis. Biological therapies can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of TNF-α (adalimumab, etanercept, infliximab) and the inhibitors of IL-12 and -23 (ustekinumab). Efalizumab is a humanized recombinant monoclonal IgG1 antibody. It targets multiple stages in the immunopathogenesis of psoriasis: initial T-cell activation, migration of T-cells into dermal and epidermal tissues, and T-cell reactivation. On 19 February 2009, the Committee for Medicinal Products for Human Use (CHMP) recommended the suspension of the marketing authorisation for efalizumab. AREAS COVERED: Numerous clinical trials have demonstrated the efficacy, safety and health-related quality of life benefits of efalizumab in patients with moderate-to-severe chronic plaque psoriasis. Efalizumab was approved by the FDA in November 2003 and by the European Medicines Evaluation Agency in September 2004 for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. Recently, three cases of progressive multifocal leukoencephalopathy were described in patients on long-term (> 3 years) efalizumab therapy, leading to its withdrawal from the market. EXPERT OPINION: Although initially favorable, the safety profile of efalizumab revealed the appearance of severe adverse events in long-term treated patients. Therefore, post-marketing surveillance is essential for correct evaluation of drug potential.     

Advancements in the treatment of psoriasis: role of biologic agents

OBJECTIVE: To evaluate the role of biologic agents as antipsoriatic therapy. SUMMARY: Mild psoriasis can generally be managed with topical therapy. Moderate-to-severe psoriasis has traditionally been treated with systemic therapies such as cyclosporine, methotrexate, retinoids, and phototherapy (ultraviolet B, psoralen plus ultraviolet A). The treatments for moderate-to-severe psoriasis often do not meet patient and physician expectations because of significant side effects (e.g., organ toxicity, skin cancer), lack of durable efficacy, and inconvenient administration schedules (e.g., daily dosing, multiple weekly exposures). The recognition of psoriasis as a T-cell.mediated disease has led to the development of biologic agents that more specifically target key steps in the pathologic process. A review of the literature was conducted to identify randomized controlled trials that have been published on the efficacy, safety, and quality-of-life effects of both approved and investigational biologics for the treatment of psoriasis. The first 2 biologic agents for the treatment of moderate-to-severe chronic plaque psoriasis were approved by the U.S. Food and Drug Administration (FDA) in 2003, alefacept in January and efalizumab in October. Both agents have demonstrated favorable safety profiles in clinical trials and significant benefits on patient quality of life. Head-to-head trials are lacking, but in placebo controlled trials, similar percentages of patients appear to respond to each of these 2 drugs. An advantage of alefacept is that it has been shown in clinical trials to provide durable off-treatment efficacy (approximately 7 months). Efalizumab has a relatively quick onset of antipsoriatic effect, but it needs to be administered once weekly continuously to maintain symptom control. Etanercept (approved by the FDA for treating moderate-to-severe plaque psoriasis in May 2004) and infliximab (not FDA-approved for psoriasis treatment) have also shown promise in randomized controlled trials, although less data are available on these agents. Case reports and pilot studies suggest that other biologics under investigation may also prove useful for the treatment of psoriasis. Patient populations that may particularly benefit from biologic therapy are discussed. CONCLUSION: Biologic agents appear to offer a safe and effective alternative to conventional systemic therapies and phototherapy for the treatment of moderate-to-severe chronic plaque psoriasis. The biologics appear to be safer than traditional therapies, although long-term safety data still need to be established.     

他克莫司软膏治疗斑块状寻常型银屑病18例

目的 观察他克莫司软膏治疗斑块状寻常型银屑病的，临床疗效及安全性。方法 将36例斑块状银屑病患者随机分治疗组和对照组各18例，治疗组采用0．1％他克莫司软膏和尿素软膏外涂，bid，共治疗4周；对照组用糠酸莫美松软膏和尿素软膏外涂，bid，共治疗4周。用PASI积分评价疗效，并观察不良反应。结果 治疗组治疗结束时有效率为94．4％，对照组为66．7％（P〈0．05）。治疗组起效时间平均约为10d，对照组为14d。治疗组发生皮肤刺激反应5例（27．8％）。结论 他克莫司软膏外用治疗斑块状寻常型银屑病具有良好疗效和安全性。     

A safety review of recent advancements in the treatment of psoriasis: analysis of clinical trial safety data

Introduction: The management of psoriasis can include oral medications and injectable biologics. Safety data of these various treatment options are important to consider when choosing the right treatment for the patient.

Areas covered: This review evaluates the safety of newer treatments approved for psoriasis, including interleukin-(IL)-17 inhibitors, IL-23/p19 inhibitors, ustekinumab, certolizumab pegol and apremilast, using phases III and IV clinical trial data.

Expert opinion: Even as treatment of psoriasis becomes safer, it is important to recognize both common and uncommon adverse effects of treatment. Common adverse effects are similar across treatment options, including upper respiratory infection and injection-site reaction. Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast. While IL-23/p19 inhibitors may have a slightly better safety profile than other biologics, long-term data are limited. The conclusions that can be drawn from clinical trial safety data are limited given that many clinical trials are not large enough to detect rare safety events. Data from registries provide important complementary information on long-term safety but there are limitations including a lack of randomized assignment between drug treatments.     

The safety of ustekinumab for the treatment of psoriatic arthritis

Introduction: The cytokines interleukin (IL)-12 and IL-23 have been involved in the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their receptors, blocking the T1 and T17 inflammatory pathways. Ustekinumab has been evaluated for the treatment of various chronic immune mediated diseases including psoriasis and psoriatic arthritis (PsA). Most of the data regarding the safety of ustekinumab come from the experience treating patients with psoriasis, but clinical trials have demonstrated its efficacy and safety in the treatment of both diseases. The most common adverse events observed during the clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headache and injection site reactions. Throughout long-term ustekinumab treatment, serious infections or major cardiovascular adverse events occurred rarely.

Areas covered: In this review we report the safety data that come from phase II and phase III clinical trials that assay the efficacy and safety of ustekinumab in PsA, including recently published data corresponding to long-term studies. Relevant references were obtained through a literature search in MEDLINE/Pubmed (search strategy: ustekinumab AND psoriatic arthritis) for articles published until November 2016, complemented by a manual search.

Expert opinion: In clinical practice, ustekinumab is generally a well-tolerated treatment, and the safety profile in psoriatic arthritis is similar to that reported in plaque psoriasis.     

Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis

ABSTRACT

Introduction: Primary endpoints and inclusion/exclusion criteria of biologics and small oral molecules for psoriasis treatment have been evolving due to a better understanding of the pathogenesis and potential risks.

Areas covered: We analyzed the designs of key phase 3 pivotal trials of all biologics and small oral molecules approved for moderate to severe plaque psoriasis from published data on the ClinicalTrials.gov website and literature in the PubMed database. Alefacept, efalizumab, anti-tumor necrosis factors, anti-interleukin (IL)-12/IL-23, anti-IL-17 and anti-IL-23 inhibitors were discussed chronologically. Small oral molecules including tofacitinib and apremilast were also reviewed.

Expert opinion: The primary endpoints of trials of biologics have been raised progressively and psoriasis area and severity index (PASI) 100 can now be readily achievable by the recent biologics. For safety, 5-year observation periods have become a gold standard after the report of progressive multifocal leukoencephalopathy after efalizumab. Also, the need for tuberculosis (TB) prophylaxis has also been relaxed in one trial of risankizumab. Small oral molecules are the future of affordable effective treatment for psoriasis, but the safety concerns must be overcome as reflected by their more stringent exclusion criteria. More biologic switch data and inclusion of patients previously excluded, e.g. viral hepatitis, are still needed.     

注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合清热凉血方治疗中重度难治性银屑病的临床疗效观察

目的 探讨注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（益赛普）联合中药清热凉血方治疗中重度难治性银屑病的疗效和安全性.方法 选取中日友好医院皮肤科30例中重度银屑病患者,完全随机分为益赛普联合清热凉血方组、阿维A联合清热凉血方组和清热凉血方组,每组10例.益赛普联合中药组在口服中药清热凉血方的基础上予以益赛普50 mg皮下注射,每周1次;阿维A联合清热凉血方组为口服中药基础上每日口服阿维A胶囊30 mg,1次/d;清热凉血方组给予中药清热凉血方治疗,每日2次;疗程均为12周.观察3组患者治疗4、8、12周后银屑病皮损面积和严重程度指数（PASI）、患者整体评价（PGA）、视觉模拟评分（VAS）、生活质量评分及不良反应.结果 治疗12周后,益赛普联合清热凉血方组、阿维A联合清热凉血方组和清热凉血方组的PASI、PGA、VAS评分较治疗前明显降低[PASI评分：（4.6±1.0）分比（28.7±2.3）分,（15.0±0.9）分比（31.9±2.1）分,（19.0±1.7）分比（26.8±1.7）分;PGA评分：（1.40±0.22）分比（5.20±0.20）分,（3.10±0.18）分比（5.60±0.22）分,（4.00±0.21）分比（5.20±0.20）分;VAS评分：（2.20±0.44）分比（7.40±0.43）分,（4.40±0.16）分比（7.90±0.41）分,（5.50±0.27）分比（6.90±0.38）分]（P＜0.05）.治疗8周后,益赛普联合清热凉血方组和阿维A联合清热凉血方组PASI[（9.8±1.3）、（19.2±0.9）分]、PGA[（2.60 ±0.31）、（4.00±0.15）分]、VAS[（4.20±0.33）、（5.20±0.25）分]评分均低于治疗前（P＜0.05）;治疗4周后,益赛普联合清热凉血方组的PASI[（16.6±1.7）分]、PGA[（3.80 ±0.33）分]、VAS[（5.40 ±0.16）分]评分均低于治疗前,阿维A联合清热凉血方组PASI[（27.5±1.7）分]评分低于治疗前,差异均有统计学意义（均P＜0.05）.益赛普联合清热凉血方组治疗4、8、12周后的PASI、PGA、VAS评分和阿维A联合清热凉血方组治疗后8、12周的PASI、PGA、VAS评分均低于清热凉血方组同期指标（均P＜0.05）.益赛普联合清热凉血方组治疗4、8、12周后PASI评分与阿维A联合清热凉血方组比较,差异均有统计学意义（均P＜0.05）.益赛普联合清热凉血方组、阿维A联合清热凉血方组和热凉血方组治疗12周后生活质量评分与治疗前比较,差异有统计学意义[（3.2±0.9）分比（25.1±3.1）分,（16.1±1.6）分比（30.4±2.0）分,（18.9±2.0）分比（25.8±1.7）分]（P＜0.05）.益赛普联合清热凉血方组和阿维A联合清热凉血方组的生活质量评分均低于清热凉血方组,差异有统计学意义（P＜0.05）;益赛普联合清热凉血方组的生活质量评分明显低于阿维A联合清热凉血方组,差异有统计学意义（P＜0.05）.结论 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中重度的银屑病,起效迅速、疗效好,是顽固难治性银屑病的治疗方法的选择,其长期疗效以及安全性有待进一步观察.     

The safety of ustekinumab in psoriasis

Ustekinumab is effective in the treatment of a variety of autoimmune conditions including psoriasis. As a relatively new therapeutic agent, its long-term effects are still under investigation. Short-term studies, however, have revealed ustekinumab to be generally well tolerated and safe. This article provides a comprehensive review of the pharmacokinetics of ustekinumab, its safety profile, adverse effects, and use in pregnancy. The effect of diabetes and prior immunosuppressant therapy is also addressed.     

白芍总苷联合补骨脂注射液治疗寻常型银屑病的疗效观察

目的:观察白芍总苷(TGP)联合补骨脂注射液治疗寻常型银屑病的疗效和安全性。方法:将189例寻常型银屑病患者分为2组,治疗组97例,口服TGP联合应用补骨脂注射液;对照组92例,仅应用补骨脂注射液。2组疗程均为4周。观察2组治疗效果及不良反应发生情况。结果:治疗组总有效率为88.66%,明显高于对照组(67.40%)。治疗组治疗后银屑病面积与严重程度指数(PASI)评分亦显著低于对照组。2组均未见严重不良反应发生。结论:TGP联合补骨脂注射液治疗寻常型银屑病有较好临床疗效,并可减少补骨脂注射液的副作用。     

古塞奇尤单抗治疗中重度斑块状银屑病有效性和安全性的系统评价

目的:系统评价古塞奇尤单抗治疗中重度斑块状银屑病的有效性和安全性,为临床提供循证参考。方法:计算机检索PubMed、Embase、Cochrane图书馆、中国知网、维普网、万方数据等数据库,检索时限均为建库起至2019年10月,纳入古塞奇尤单抗对比安慰剂或阳性对照药治疗中重度斑块状银屑病的随机对照试验(RCT),筛选文献并提取资料后,采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具进行质量评价,使用Stata 16.0软件进行Meta分析。结果:共纳入8项RCT,合计3488例患者。结果显示,古塞奇尤单抗组患者的银屑病皮损面积和严重程度指数(PASI)评分较基线下降≥90%的患者比例均显著高于安慰剂组[RR=26.72,95%CI(15.98,44.70),P<0.001]、阿达木单抗组[RR=1.45,95%CI(1.32,1.59),P<0.001]和司库奇尤单抗组(P<0.0001),该组研究者全面评估(IGA)评分为0或1分(清除/几乎清除)的患者比例亦均显著高于安慰剂组[RR=11.15,95%CI(8.22,15.14),P<0.001]和阿达木单抗组[RR=1.27,95%CI(1.19,1.35),P<0.001]。此外,在IGA评分为0分(清除)的患者比例、PASI评分较基线下降≥75%的患者比例、皮肤病生活质量指数评分为0或1分的患者比例等方面,古塞奇尤单抗组均显著优于安慰剂和阿达木单抗组;在PASI评分较基线下降100%的患者比例方面,古塞奇尤单抗组也显著优于安慰剂组(P<0.05),但与阿达木单抗组比较差异无统计学意义(P>0.05);而古塞奇尤单抗IGA评分为0分(清除)的患者比例等次要结局指标与司库奇尤单抗组比较差异均无统计学意义(P>0.05)。在总不良反应发生率、因不良反应退出率等安全性指标方面,古塞奇尤单抗组与安慰剂或阿达木单抗组比较差异均无统计学意义(P>0.05)。结论:古塞奇尤单抗在改善中重度斑块状银屑病患者症状方面的效果优于安慰剂、阿达木单抗和司库奇尤,且安全性良好。     

窄谱中波紫外线单一治疗重度银屑病

目的评价窄谱中波紫外线（NB—UVB）单一治疗重度银屑病的临床疗效。方法按照治疗方案规律接受NB—UVB治疗的斑块型银屑病患者83例,根据病情严重程度分为轻中度组[银屑病面积及皮损严重指数（PASI）评分〈15,33例）和重度组（PASI评分≥15,50例）。治疗第2…468、12周对患者进行疾病严重程度评价（PASI评分）,并记录不良事件及合并用药。研究结束后对治疗的有效性和安全性进行统计分析及评价,第8周作为主要疗效分析终点。结果治疗第8周轻中度组的PASI的下降比例为68．2（60．0％,78．6％）,重度组为77．5％（51．0％,88．4％）,均明显优于第4周。轻中度组PASI75、PASI90的比例为45．5％（15例）、21．2％（7例）,而重度组PASI75、PASI90的比例为56．0％（28例）、28．0％（14例）。第2周时,轻中度组PASI下降比例22．8％（10．0％,46．3％）及PASI75的比例（12．1％）均明显高于重度组[13．4％（0．0％,27．1）,0％]。不良反应主要为轻度红斑及水肿,轻中度组轻度红斑4例（12．1％）,共11例次（1．9％）;重度组轻度红斑5例（10．0％）,共16例次（1．4％）,重度红斑l例（2．0％）,共1例次（0．1％）。轻中度组轻度水肿1例（3．0％）,共7例次（1．2％）;重度组3例（6．0％）,共12例次（1．1％）。重度组发生治疗后轻度瘙痒1例（2．0％）,共1例次（0．1％）。结论NB—UVB单一治疗对轻中度及重度寻常型银屑病均具有叮靠的疗效,重度银屑病患者对NB—UVB的治疗反应并不亚于轻中度患者。轻中度银屑病在治疗早期改善速度快于重度银屑病患者。     

Efalizumab: new drug. Plaque psoriasis: too many unknowns

(1) Plaque psoriasis is a chronic skin disease for which there is no definitive treatment. Topical therapy is usually tried first. (2) Efalizumab is an immunosuppressant drug marketed for the treatment of adults with moderate to severe plaque psoriasis, when other systemic treatments (ciclosporin and methotrexate) or phototherapy (PUVA therapy, etc.) are ineffective or contraindicated. (3) Clinical evaluation of efalizumab is based on 5 double-blind placebo-controlled trials. In 4 of these trials the endpoint for efficacy was the number of patients who had an improvement of at least 75% in the psoriasis area severity index (PASI) score after 12 weeks of treatment. With efalizumab 1 mg/kg per week, about 25% of patients reached this target, compared with about 4% of patients in the placebo group. Efficacy was not improved by doubling the efalizumab dose. Another trial focused on adverse effects. (4) Most patients relapsed within an average of two months following treatment withdrawal. Some patients worsened after stopping treatment. (5) The most frequent short-term adverse effect is a flu-like syndrome, which affects about 50% of patients. Adverse events observed in clinical trials included skin cancer, severe infections, aggravation or rebound of psoriasis after treatment cessation, thrombocytopenia, hyperleukocytosis, hypersensitivity reactions, and elevated liver enzyme levels. (6) In France treatment cost is around 1000 euros per month, a bit less than etanercept treatment. (7) In practice, efalizumab currently has no place in the treatment of plaque psoriasis in adults, partly due to the absence of comparisons with existing treatments, and partly because of the risk of serious adverse effects.     

An attempt to formulate an evidence-based strategy in the management of moderate-to-severe psoriasis: a review of the efficacy and safety of biologics and prebiologic options

Psoriasis is a chronic skin disorder affecting up to 2.5% of the world's population. Despite the myriad treatment options available, there is no uniformly accepted therapeutic approach for moderate-to-severe psoriasis. The objective of this review is to evaluate the relative efficacy and safety of available therapeutic options and to formulate general recommendations for the treatment of moderate-to-severe psoriasis. MEDLINE and Evidence Based Medicine (Cochrane) were used to perform a comprehensive search of the literature from 1986 to 2006. The most scientifically rigorous clinical trial published in the literature was selected for Psoriasis Area and Severity Index (PASI 75) comparison. Only information from clinical trials, human subjects and English language journals are reported in this study. The percentage of PASI 75 reduction at approximately 12 weeks obtained by the following treatment options were: Goeckerman and RePUVA, 100%; calcipotriene plus PUVA, 87%; ciclosporin, 78.2-80.3%; infliximab, 80%; adalimumab 40 mg every other week, 53% and 40 mg/week, 80%; PUVA, 63%; methotrexate, 60%; NB-UVB, 55%; acitretin 52%; etanercept 50 mg twice weekly, 49% and 25 mg twice weekly, 34%; efalizumab, 31.4%; and alefacept 21%. Psoriatic treatments with safer profiles compared with other agents include bath PUVA, Goeckerman and RePUVA. Based on the literature review of efficacy and safety of biologics and prebiologic treatment options for moderate-to-severe psoriasis, the risk:benefit ratio seems most favorable for Goeckerman and RePUVA, followed by either etanercept or adalimumab.     

白细胞介素抑制剂类生物制剂治疗斑块状银屑病的文献可视化分析

目的 分析白细胞介素（IL）抑制剂类生物制剂在斑块状银屑病治疗中的研究现状及热点。方法 检索2011年1月1日至2022年4月30日在Web of Science核心合集数据库发表的IL抑制剂类生物制剂在斑块状银屑病治疗方面的相关研究，利用CiteSpace5.8.R3软件进行文献的可视化分析，从发文量、国家/地区、机构、作者、期刊等文献关键特征分析该领域的研究现状，通过文献共被引、关键词共现、聚类及突现分析该领域的知识基础、研究热点及前沿。结果 共纳入文献2 056篇，近10年发文量呈逐年递增趋势，共计104个国家/地区的545个机构参与了IL抑制剂类药物治疗斑块状银屑病的研究，其中美国发文量805篇，占总发文量的39.15%居首位，且与德国、英国、瑞士、加拿大等有密切合作，发文最多的机构是瑞士诺华制药，发文最多的作者是德国汉堡艾本多夫医学中心的Reich K，被引频次第一的作者是加拿大Prob Med公司的Papp KA，被引频次最高的期刊为British Journal of Dermatology；该领域的研究热点主要为生物制剂治疗斑块状银屑病的作用机制、疗效及安全性研究，研究...     

A drug safety evaluation of risankizumab for psoriasis

ABSTRACT

Introduction: Risankizumab is a fully human monoclonal antibody that selectively targets interleukin (IL)-23A, interfering with the IL-23/17 axis that plays a crucial role in keratinocyte proliferation. In 2019, risankizumab was approved globally for the treatment of moderate-to-severe psoriasis.

Areas covered: The safety profile of risankizumab for the treatment of psoriasis is assessed in this review. A literature search was performed on 18 October 2019, and additional data from pooled safety analyses were evaluated.

Expert opinion: Drugs blocking the IL-23 pathway are the most recently approved treatment for psoriasis, and risankizumab seems to be the most effective one among the three IL-23 blockers approved. Risankizumab was generally well tolerated in the clinical trials and was found to be relatively safe. The safety profile of risankizumab is generally similar in clinical trials compared to adalimumab and ustekinumab. In a subset of patients with latent tuberculosis, no active tuberculosis developed after risankizumab treatment for 55 weeks without tuberculosis prophylaxis. The combination of safety, efficacy and less frequent injection (every 12 weeks) make risankizumab an attractive new choice for individuals with moderate-to-severe psoriasis. However, the long-term impact of anti-drug antibodies (24%) observed in pivotal studies as well as safety concerns in those with viral infections, hepatitis, malignancies and those in endemic tuberculosis areas, await further studies.     

Efalizumab

Introduction: Conventional systemic therapies for psoriasis are associated with serious toxicities that can limit long-term use. In recent years, biological therapies have offered the possibility of long-term therapy with improved safety and efficacy for the treatment of psoriasis. Biological therapies can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of TNF-α (adalimumab, etanercept, infliximab) and the inhibitors of IL-12 and -23 (ustekinumab). Efalizumab is a humanized recombinant monoclonal IgG1 antibody. It targets multiple stages in the immunopathogenesis of psoriasis: initial T-cell activation, migration of T-cells into dermal and epidermal tissues, and T-cell reactivation. On 19 February 2009, the Committee for Medicinal Products for Human Use (CHMP) recommended the suspension of the marketing authorisation for efalizumab.

Areas covered: Numerous clinical trials have demonstrated the efficacy, safety and health-related quality of life benefits of efalizumab in patients with moderate-to-severe chronic plaque psoriasis. Efalizumab was approved by the FDA in November 2003 and by the European Medicines Evaluation Agency in September 2004 for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. Recently, three cases of progressive multifocal leukoencephalopathy were described in patients on long-term (> 3 years) efalizumab therapy, leading to its withdrawal from the market.

Expert opinion: Although initially favorable, the safety profile of efalizumab revealed the appearance of severe adverse events in long-term treated patients. Therefore, post-marketing surveillance is essential for correct evaluation of drug potential.