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。     

生物制剂治疗银屑病的药物遗传学研究进展

研究者们发现IL-23/Th7轴在银屑病发病中具有中心地位,直接或间接靶向于此通路的生物制剂如TNF-α抑制剂、IL-12/23抑制剂、IL-17抑制剂等在治疗中重度银屑病中有明显疗效。药物遗传学通过研究药物疗效与不同个体之间基因多态性的关联,可以预测药物疗效的个体差异。生物制剂的药物遗传学研究和应用可以使银屑病的治疗更加合理及个体化,本文对生物制剂治疗银屑病的药物遗传学研究进行了综述。     

进行期寻常型银屑病患者血清TNF-α和IL-8水平检测

目的:研究进行期寻常型银屑病(acutepsoriasisvulgaris,APV)患者血清肿瘤坏死因子α(TNF-α)、白介素-8(IL-8)水平,进一步探讨银屑病的免疫学发病机制。方法:采用放射免疫-饱和液相竞争法,检测APV患者血清TNF-α、IL-8水平,并与病情严重程度皮损面积积分(PASI)进行相关性分析。结果:APV患者血清TNF-α、IL-8水平均明显高于正常人水平(P<0.01),且分别与病情严重程度皮损面积积分(PASI)呈正相关,而两者之间无明显相关性。结论:本研究表明TNF-α、IL-8可能在银屑病的发病过程中起重要的作用,TNF-αIL-8的拮抗剂可能为银屑病的治疗提供新的思路。     

生物制剂治疗泛发性脓疱型银屑病的研究进展

泛发性脓疱型银屑病(GPP)的治疗较为困难。近年来的研究表明,TNF-α、IL-17、IL-1、IL-36、IL-12/23在GPP的发病机制中均起着重要作用,可以作为GPP的特异性免疫治疗靶点。针对这些靶点的新型生物制剂如TNF-α抑制剂、IL-17抑制剂、IL-1受体拮抗剂、IL-36受体拮抗剂以及IL-12/23拮抗剂的使用,可以有效治疗该病。本文就近年来相关临床研究文献展开综述,为GPP的临床治疗提供新的思路。     

银杏石榴煎治疗银屑病疗效观察及患者血清中肿瘤坏死因子-α、白介素-6及白介素-8表达水平的变化

目的采用中药银杏石榴煎治疗进行期寻常性银屑病，观察该煎剂对银屑病疗效并检测治疗前后患者血清中肿瘤坏死因子（TNF）-α、白介素（IL）-6及IL-8表达水平变化。方法银杏石榴煎治疗前后对银屑病患者皮损进行PASI评分，采用ELISA法检测银屑病患者治疗前后和正常对照者血清中TNF—α、IL-6及IL-8的表达水平变化。结果①银杏石榴煎可显著改善银屑病患者临床症状，治疗前后PASI评分明显下降（P〈0．01）。②患者血清中TNF-α、IL-6及IL-8水平明显高于正常对照（P〈0．01），治疗后其表达水平较治疗前明显下降（P〈0．05）。③患者体内TNF-α及IL-8表达水平与PASI积分呈正相关（P〈0．05）。结论银杏石榴煎为治疗银屑病的有效药物；患者血清TNF—α、IL-6、IL-8表达水平与银屑病患者的病情变化密切相关。     

消银合剂治疗寻常性银屑病疗效及相关血清细胞因子的检测

目的 观察消银合剂对寻常性银屑病进行期的临床疗效,并探讨其对白介素(IL)-6、IL-8、IL-20及肿瘤坏死因子(TNF)-α血清细胞因子的影响.方法 选择寻常性银屑病进行期患者60例,随机分为治疗组30例和对照组30例.治疗组给予消银合剂,对照组给予复方青黛胶囊,疗程8周.观察治疗前后PASI评分的变化,并测定30例治疗组患者治疗前后及18例健康对照者血清中IL-6、IL-8、IL-20及TNF-α的水平.结果 ①治疗8周后,两组PASI积分均明显下降,治疗组PASI积分明显低于对照组(P＜0.5).②治疗组有效率63.33%,优于对照组33.33%(P＜0.05).③与健康对照组相比,患者组血清IL-6、IL-8、IL-20及TNF-α的水平明显升高(P＜0.05).治疗 8周后,患者组血清IL-6、IL-8、IL-20及TNF-α的水平明显降低,与健康对照组相比,差异无统计学意义.IL-6、IL-8、IL-20及TNF-α水平分别与PASI评分之间均呈直线正相关.结论 消银合剂治疗寻常性银屑病疗效确切,其作用机制可能与影响IL-6、IL-8、IL-20及TNF-α血清细胞因子有关.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗斑块型银屑病临床疗效相关细胞因子检测

目的探讨血清白细胞介素(IL)-12、IL-17A、IL-23和肿瘤坏死因子(TNF)-α水平在重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(商品名益赛普)治疗斑块型银屑病疗效中可能的作用。方法 40例中重度斑块型银屑病患者皮下注射益赛普25 mg/次,2次/周,连续24周;治疗前用酶联免疫吸附法(ELISA)检测患者血清IL-12、IL-17A、IL-23和TNF-α水平。记录治疗前后计算银屑病皮损面积和严重程度指数(PASI)评分。PASI评分较基线下降≥75%定义为临床疗效显著,PASI评分较基线下降75%定义为临床疗效不显著。根据临床疗效是否显著分为2组,比较2组治疗前血清IL-12、IL-17A、IL-23和TNF-α水平。结果益赛普治疗临床疗效显著组中血清IL-12水平明显高于临床疗效不显著组,差异有统计学意义;2组中IL-17A、IL-23和TNF-α水平差异无统计学意义。结论血清IL-12水平可能是评估益赛普治疗斑块型银屑病临床疗效的一个指标。     

生物制剂在银屑病中的应用进展

银屑病是一种慢性炎症性疾病,甲氨蝶呤、维A酸、环孢素等是系统治疗银屑病的传统药物,但均存在起效慢及不良反应多等缺点。生物制剂尤其是单克隆抗体是FDA批准用于治疗中～重度银屑病的常见药物,本文系统阐述TNF-α拮抗剂、IL-17拮抗剂、IL12/23拮抗剂、IL-23拮抗剂治疗银屑病的临床疗效和安全性。     

肿瘤坏死因子α拮抗剂所致皮肤不良反应及对策

肿瘤坏死因子α（TNF-α）是一种重要的细胞因子,在很多炎症性疾病中发挥重要作用。TNF-α拮抗剂作为生物制剂,近年来越来越多地用于类风湿关节炎、强直性脊柱炎［１］、克罗恩病、银屑病性关节炎、银屑病等疾病的治疗中。目前在我国上市的TNF-α拮抗剂包括益赛普（etanercept）、英夫利西单抗（infliximab）、阿达木单抗（adalimumab）三种,还有两种新型的TNF-α拮抗剂--赛妥珠（certolizumab）和戈利木（golimumab）已在国外上市。TNF-α拮抗剂的疗效与不良反应在既往的文献中已有较多报道,本文仅就其诱发的皮肤不良反应及对策做一综述……     

关节病性银屑病遗传学发病机制和治疗进展

关节病性银屑病是一种慢性炎症性关节病变,与该病发病显著相关的易感基因或易感位点有IL-23R、IL-12B、HLA-Cw6、TRAF3IP2、NO、FBXL19、PSMA6-NFKBIA附近区域,可能相关的易感基因有IL-23A、TNIP1、TNF*-857T、LCE3C-LCE3Bdel变异体、REL基因、IL-13.针对关节病性银屑病发病环节中的一些重要免疫分子或免疫细胞,多种靶向生物制剂包括细胞因子拮抗剂(英夫利西、益赛普、阿达木、戈利木、优斯它单抗)、磷酸二酯酶抑制剂、T细胞抑制剂(阿贝西普)和B淋巴细胞耗竭剂(利妥昔单抗)用于该病的治疗,疗效好,安全性较高.     

Biological therapy in genital psoriasis in women

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA‐G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA‐G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti‐IL17 (Secukinumab, Ixekizumab) and anti‐IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti‐TNFα patients, 6 anti‐IL17 and 1 anti‐IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA‐G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.     

寻常型银屑病患者中性粒细胞分泌炎性因子的研究

目的观察寻常型银屑病患者外周血中性粒细胞是否存在分泌炎性因子的异常,探讨中性粒细胞参与银屑病的机制。方法作中性粒细胞培养,应用酶联免疫吸附法检测脂多糖(LPS)刺激前后中性粒细胞分泌白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)的水平,应用细胞色素C还原法检测LPS刺激前后中性粒细胞超氧阴离子(Superox-ide anion)的水平。结果在脂多糖刺激前、后,银屑病患者外周血中性粒细胞分泌的IL-8、TNF-α以及Superoxide anion水平均较正常人显著增高(P<0.05),且进行期患者上述炎性因子的分泌水平显著高于静止期患者(P<0.01)。银屑病患者病情严重程度(PASI评分)与中性粒细胞于脂多糖刺激前、后IL-8、TNF-α及Superoxideanion水平均呈正相关(P<0.05)。结论银屑病患者存在外周血中性粒细胞分泌炎性因子的异常,该种异常可能参与银屑病的发病与病情进展,其中可能有感染因素的介导。     

司库奇尤单抗治疗儿童银屑病六例疗效评价

目的：评价司库奇尤单抗注射液治疗儿童银屑病的临床疗效及安全性。方法：收集2020年1月1日至2020年5月1日传统治疗方法不佳的儿童银屑病患者,在第0、1、2、3、4周进行皮下注射司库奇尤单抗150 mg,每周一次,共5次。记录患者PASI及BSA评分。结果：司库奇尤单抗共治疗6例儿童银屑病,治疗第4周时,6例患者均达到PASI 90,BSA显著降低,未出现不良反应。结论：司库奇尤单抗注射液治疗儿童银屑病安全有效。     

Efficacy and safety of etanercept in the treatment of recalcitrant psoriasis: An open-label,retrospective, observational study in Taiwan

BackgroundPsoriasis is a chronic inflammatory disease affecting the quality of life of patients. Traditional treatments are limited by adverse side effects. Etanercept is a biological agent used as an alternative treatment for psoriasis.MethodsThis open-label, observational study conducted in Taiwan involved 22 patients with recalcitrant psoriasis who received a 24-week treatment with etanercept—50 mg twice weekly (BIW) during the first 12 weeks and 25 mg BIW in the next 12 weeks. Psoriasis Area and Severity Index (PASI) score at Weeks 0, 12, and 24 were recorded. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and tumor necrosis factor-alpha (TNF-α) at baseline, Week 12, and Week 24 were obtained. Adverse events and blood tests were recorded as safety assessment.ResultsAt Week 12, 54.5% and 13.6% patients achieved ≥50% improvement from baseline in PASI score (PASI 50 and PASI 75, respectively); at Week 24, 66.7% and 23.8% patients achieved PASI 50 and PASI 75, respectively. The mean improvement in PASI was 49.8% at Week 12 and 59.8% at Week 24, while 100% and 62.5% patients had reduced ESR and CRP levels, respectively. There were no deaths or serious adverse events. Four patients developed positive ANA, one of whom had poor psoriasis control. Most patients (93.8%) had higher serum TNF-α levels compared to baseline.ConclusionsEtanercept is effective and safe in treating recalcitrant psoriasis, reduces ESR and CRP levels, and occasionally induces positive ANA titer associated with poor psoriasis control. Serum TNF-α level may increase after treatment, but this does not seem to affect PASI improvement.     

Real-world evidence of secukinumab in psoriasis treatment – a meta-analysis of 43 studies

Real-world evidence (RWE) meta-analyses provide valuable insights from patients in routine clinical practice. Secukinumab, the first fully human monoclonal antibody that neutralizes IL-17A, has shown long-lasting effectiveness and safety in plaque psoriasis (PsO). Since its licence approval in 2015, many RWE studies have been published. The objective of this study was to review all available literature on RWE studies with secukinumab and the secukinumab arm of comparator studies in patients with moderate-to-severe PsO to evaluate its effectiveness, drug survival and safety. https://www.embase.com and https://clinicaltrials.gov databases were searched using prespecified inclusion criteria between 1 January 2015 and 31 May 2019. Using a meta-package and R statistical software to analyse data, key outcomes were measured at 3, 6 and 12 months. PASI and DLQI score data were recorded for patients who remained on secukinumab treatment. Overall, 43 studies were included. Drug survival was 90% at 3 and 6 months, and 80% at 12 months. At 12 months, 8% of patients had discontinued treatment due to lack of effectiveness. At 3, 6 and 12 months, Psoriasis Area and Severity Index (PASI) 90 scores were as follows: 50%, 53% and 60%, and PASI 100 scores were 36%, 46% and 51%, respectively. At 3, 6 and 12 months, 57%, 55% and 65% of patients achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, respectively. Adverse events were consistent with rates observed in clinical trials with no new safety signals. This meta-analysis strengthens existing evidence on the clinical effectiveness of secukinumab in patients with moderate-to-severe PsO, demonstrating high drug survival rates, high levels of patient-reported outcomes, and good tolerance.     

开玄解毒法干预斑块型银屑病皮损部位肿瘤坏死因子-α、白细胞介素-8,P物质含量的动态变化

目的观察“开玄解毒法”治疗斑块型银屑病过程中，皮损部位肿瘤坏死因子（TNF-α）、白细胞介素-8（IL-8）、P物质（SP）含量的动态变化情况，进而探讨该方法治疗斑块型银屑病的作用机制。方法对12例斑块型银屑病患者采用“开玄解毒法”（口服“开玄解毒方”结合刺络放血疗法）连续治疗3周，以银屑病皮损面积和严重程度（PASI）评分进行疗效评价；每次刺络放血疗法后（共5次）采集患者治疗过程中皮损部位释放出的末梢血，用ELISA双抗体夹心法检测TNF-α、IL-8、SP的含量，分别绘制每例患者治疗过程皮损部位TNF-α、IL-8、SP含量的变化曲线图，了解“开玄解毒法”对斑块型银屑病皮损处TNF-α、IL-8、SP的干预作用。结果“开玄解毒法”治疗斑块型银屑病的总有效率为66．67％，治疗后PASI评分较治疗前显著下降（P=0．005）；治疗过程中皮损PASI评分、TNF-α与IL-8在皮损部位的含量呈逐渐下降趋势；但SP在皮损部位的含量无显著变化。结论“开玄解毒法”治疗斑块型银屑病有效，可能与降低皮损处TNF-α与IL-8含量有关，但尚不能认为该法可以降低皮损部位SP的含量。     

痤疮患者血清H_2S水平检测及与IL-6和TNF-α水平的相关性

目的:检测痤疮患者血浆H2S水平及确定与IL-6和TNF-α水平的相关性。方法:采用亚甲基染色法检测67例痤疮患者(轻度31例、中度21例、重度15例)及20名健康体检者血清H2S水平,ELISA检测血清IL-6和TNF-α水平。结果:痤疮患者血清H2S平均水平为(13.79±4.19)μmmol/L,显著低于对照组的(22.23±4.52)μmmol/L(P0.001);血清IL-6及TNF-α平均水平分别为(89.72±31.68)pg/mL及(61.17±23.81)pg/mL,高于对照组的(27.32±4.26)pg/mL和(22.73±14.33 pg/mL)(P0.001)。痤疮患者血浆H2S水平与IL-6和TNF-α浓度均呈显著负相关(均P0.001)。结论:血浆H2S可能参与痤疮炎症的发病过程。     

寻常型银屑病患者外周血中白介素-35表达水平的检测

目的：检测寻常性银屑病患者外周血中白细胞介素35（IL-35）水平。方法：应用双抗体夹心酶联免疫吸附法(ELISA)检测30例寻常型银屑病患者外周血清中IL-35的水平。结果：与正常人对照组相比,寻常型银屑病患者血浆IL-35 水平显著降低,进行期患者组显著低于静止期患者组(P<0.05)。IL-35 血清水平与寻常型银屑病严重程度指数有相关性（正相关还是负相关？）（P<0.05）。结论：IL-35在寻常型银屑病的发病中可能起重要作用。     

银屑病患者外周血Th17/Th22细胞的表达

目的:检测寻常性银屑病(PV)患者外周血Th17、 Th22的水平及相关因子IL-17、IL-22 、IL-6的血清水平。方法: PASI评分评估患者病情,采用流式细胞术检测40例PV患者和30例健康对照者外周血Th17和Th22细胞,ELISA法检测血清中IL-17、IL-22和IL-6水平。结果: PV患者Th17细胞及Th22细胞,血清IL-17、IL-22及血清IL-6的水平明显高于健康对照组比较（P均<0.01）,且与PASI呈正相关（P＜0.05）。结论:Th17和Th22可能参与银屑病的发病。