注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中、重度寻常性银屑病疗效观察

目的：评价注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（商品名：益赛普）治疗中、重度寻常性银屑病患者的疗效。方法：采用多中心、随机、双盲、双模拟、阳性平行对照临床试验方法，对144例中、重度寻常性银屑病患者进行银屑病皮损面积和严重度指数（PASI）评分，其中益赛普组72例，甲氨蝶呤（MTX）组72例。结果：144例患者中124例完成了12周的治疗。治疗12周后，益赛普组PASI50、PASI75、PASI90的比例（PP人群）高于MTX组，差异具有统计学意义（P〈0．01）。益赛普组从第4周起PASI评分的改善优于MTX组。且对躯干、四肢的疗效好于MTX组。结论：与MTX比较，益赛普具有起效快、治疗效果明显、PASI评分改善明显的特点。     

肿瘤坏死因子拮抗剂治疗重症三氯乙烯药疹样皮炎

【摘要】 目的 观察肿瘤坏死因子拮抗剂在重症三氯乙烯药疹样皮炎治疗中的作用。 方法 5例以皮疹、发热、浅表淋巴结肿大和肝、肾损害为主要表现的重症三氯乙烯药疹样皮炎患者,在判断无肿瘤、结核及重症感染后,3例采用肿瘤坏死因子拮抗剂25 mg皮下注射,每周2次,联合糖皮质激素治疗;2例单独使用肿瘤坏死因子拮抗剂治疗。 结果 肿瘤坏死因子拮抗剂联合糖皮质激素治疗的3例患者体温在1周内降至正常,住院期间未发生感染、急性肝功能衰竭等,出院时皮疹消退,口腔、外阴等黏膜恢复正常,肝肾功能正常,平均住院时间36 d。单独使用肿瘤坏死因子拮抗剂的2例患者均治愈,临床疗效与联合糖皮质激素治疗的患者无明显差别,治疗后28周测得血清肿瘤坏死因子α水平降至正常。 结论 在重症三氯乙烯药疹样皮炎的治疗过程中尽早、足量使用肿瘤坏死因子拮抗剂有益于快速控制病情。     

肿瘤坏死因子α拮抗剂治疗一例伴嗜酸性粒细胞增多和系统症状药疹的临床观察

【摘要】 报告单独使用肿瘤坏死因子α成功治愈别嘌醇导致伴嗜酸性粒细胞增多和系统症状的药疹（DRESS）的经过。男性痛风患者,60岁,发病前20 d口服别嘌醇,发热、全身皮疹伴有肝肾功能损害、白细胞和嗜酸性粒细胞升高、淋巴结肿大,合并糖尿病。经皮下注射益赛普25 mg（首剂加倍）,隔天1次,共8次,获得痊愈。首次注射后,发热即控制;1 d 后皮损不再扩大,2 d 后皮损开始脱屑,5 d 后表皮新生;外周血肿瘤坏死因子α逐渐下降,治疗5周降至正常范围。入院后外周血白细胞、C反应蛋白、胆红素仍持续上升,在注射3次后开始下降,2周内逐渐恢复。转氨酶在首次注射后开始下降,2周内恢复。外周血嗜酸性粒细胞在首次注射后持续上升,于第10天达高峰,之后缓慢下降,治疗5周后降至正常范围。提示,肿瘤坏死因子拮抗剂能在疾病早期快速、安全、有效地控制伴嗜酸性粒细胞增多和系统症状的药疹,但不能阻止嗜酸性粒细胞上升。 【关键词】 皮炎,剥脱性; 肿瘤坏死因子α; 治疗结果     

肿瘤坏死因子α拮抗剂治疗一例伴嗜酸性粒细胞增多和系统症状药疹的临床观察北大核心CSCD

报告单独使用肿瘤坏死因子α成功治愈别嘌醇导致伴嗜酸性粒细胞增多和系统症状的药疹（DRESS）的经过。男性痛风患者,60岁,发病前20d口服别嘌醇,发热、全身皮疹伴有肝肾功能损害、白细胞和嗜酸性粒细胞升高、淋巴结肿大,合并糖尿病。经皮下注射益赛普25mg（首剂加倍）,隔天1次,共8次,获得痊愈。首次注射后,发热即控制;1d后皮损不再扩大,2d后皮损开始脱屑,5d后表皮新生．外周血肿瘤坏死因子α逐渐下降,治疗5周降至正常范围。入院后外周血白细胞、C反应蛋白、胆红素仍持续上升,在注射3次后开始下降,2周内逐渐恢复。转氨酶在首次注射后开始下降,2周内恢复。外周血嗜酸性粒细胞在首次注射后持续上升,于第10天达高峰,之后缓慢下降,治疗5周后降至正常范围。提示,肿瘤坏死因子拮抗剂能在疾病早期快速、安全、有效地控制伴嗜酸性粒细胞增多和系统症状的药疹,但不能阻止嗜酸性粒细胞上升。     

2016年益赛普治疗银屑病征文通知北大核心CSCD

益赛普即注射用重组人Ⅱ型肿瘤坏死因子受体一抗体融合蛋白,是国家食品药品监督管理局批准的第一个治疗银屑病的TNF-α拮抗剂。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗前后银屑病患者血清脂联素水平的变化

目的:研究分析注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(商品名,益赛普)对银屑病患者血清脂联素水平的影响。方法:将28例寻常性银屑病患者(银屑病组)及28例年龄、性别和体重指数(BMI)相匹配的健康志愿者(健康对照组)纳入研究,银屑病严重性评级指标采用银屑病皮损面积和严重程度指数(PASI)及体表受累面积(BSA)评分,所有患者均给予益赛普50 mg,皮下注射,每周1次。对所有银屑病患者治疗前、治疗后12周、24周与健康对照组的血清脂联素水平进行随访检测。结果:银屑病组血清脂联素水平较健康对照组明显降低,差异有统计学意义(P0.05)。经过12周的益赛普治疗后,银屑病组血清脂联素水平较治疗前升高,但差异无统计学意义(P0.05),经过24周的益赛普治疗后,银屑病组血清脂联素水平较治疗前及治疗12周后均有明显升高,差异有统计学意义(P0.05),与健康对照组相比差异无统计学意义。结论:脂联素与银屑病的发病可能具有相关性,使用益赛普治疗银屑病,可降低银屑病患者代谢综合征的发生率。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗银屑病及其对白细胞介素17A和肿瘤坏死因子α的影响

目的 探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc,商品名益赛普)联合甲氨蝶呤对中重度斑块型银屑病患者血清和单个核细胞中白细胞介素(IL) 17A和肿瘤坏死因子(TNF-α)的影响.方法 2014年8月至2016年2月同济大学附属第十人民医院皮肤科门诊收治的30例中重度斑块型银屑病患者,分为益赛普组(15例)和益赛普+甲氨蝶呤组(15例),疗程24周.采用酶联免疫吸附法(ELISA)和实时定量PCR法检测两组患者治疗前后血清和外周血单个核细胞的IL-17A和TNF-α的浓度和mRNA表达水平.结果 治疗前益赛普+甲氨蝶呤组和益赛普组患者,血清IL-17A,TNF-α水平以及外周血PBMC中IL-17A,TNF-α mRNA的表达均显著高于健康对照组(P＜0.05);治疗后,益赛普+甲氨蝶呤组血清IL-17A、TNF-α浓度(142.67±14.82,70.07±25.02)及外周血PBMC中IL-17A、TNF-α mRNA表达(1.12±0.33,2.50±1.04)与益赛普组血清IL-17A、TNF-oα浓度(163.54±23.18,91.98±14.62)及外周血PBMC中IL-17A、TNF-α mRNA的表达(1.56±0.77,3.61±2.14)比较显著下降(P＜0.05).结论 益赛普联合甲氨喋呤治疗银屑病疗效优于单用益赛普治疗,联合治疗可以缩短治疗时间,提高疗效,其作用机制可能与下调IL-17A、TNF-α的表达量有关.     

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。     

SCORTEN评分对中毒性表皮坏死松解症和Stevens-Johnson综合征评估分析

目的 分析SCORTEN评分对中毒性表皮坏死松解症和Stevens?Johnson综合征患者预后评估的准确性。方法 回顾性分析1992年4月至2014年3月期间在北京协和医院收治的中毒性表皮坏死松解症和Stevens?Johnson综合征39例,其中死亡病例13例,按照年龄分层1∶2匹配诊断明确好转出院26例。39例患者用SCORTEN评分系统评分,计算预期死亡数,比较39例各级分层的预期死亡数与实际死亡数,绘制受试者工作特征曲线（ROC曲线）,评估SCORTEN评分的判断力。结果 39例患者中,按SCORTEN评分系统评为1分15例,2分14例,3分6例,4分4例,总预期死亡6.808例,实际死亡13例。 每个积分层预期死亡数与实际死亡数差异无统计学意义。SCORTEN评分系统的ROC曲线下面积 = 0.832 8,表明有较好的预测能力。结论 SCORTEN评分系统可在早期对中毒性表皮坏死松解症和Stevens?Johnson综合征患者死亡率作出评估。     

SAPHO综合征14例临床特征与治疗

目的 探讨SAPHO综合征患者的临床特征。方法 对14例SAPHO综合征患者的临床资料、治疗方案及临床疗效进行回顾性分析。结果 本组14例患者中男8例，女6例，平均发病年龄(28.43±13.38)岁。14例均有皮肤损害(掌跖脓疱病8例，寻常型痤疮2例，囊肿型痤疮3例，聚合型痤疮1例)。影像学中病变累及的骨关节依次为胸前壁(13/14)、骶髂关节(11/14)、四肢骨关节(6/14)、脊柱(6/14)、肩关节(3/14)、骨盆(2/14)。13例患者单用或联合使用非甾体类抗炎药、糖皮质激素、改善病情的抗风湿药和肿瘤坏死因子-α(TNF-α)拮抗剂治疗，其中9例患者先后联合TNF-α拮抗剂治疗。对13例患者进行随访，9例患者单用或联合糖皮质激素、非甾体类抗炎药和DMARDs治疗后皮肤损害或骨关节肿痛症状控制欠佳，其中5例联合TNF-α抑制剂治疗后皮肤和骨关节症状均有不同程度改善，2例患者联合使用英夫利西单抗后皮疹加重后改为益赛普，1例拒绝治疗。结论 本组SAPHO综合征男性多见，主要受累的骨关节是前胸壁，皮肤损害主要表现为掌跖脓疱病，且多见于女性，重度痤疮多见于男性。TNF-α拮抗剂对难...     

Rapid remission of Stevens–Johnson syndrome by combination therapy using etanercept and intravenous immunoglobulin and a review of the literature

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are spectrum of rare, acute, and life‐threatening delayed‐type drug hypersensitivity reactions that are associated with high mortality rates. However, no therapeutic standard has been proposed for SJS/TEN. Here, we report a case of a patient diagnosed with Stevens–Johnson syndrome whose disease progression was halted by a single dose of etanercept and was treated successfully. In addition, we reviewed the literature reporting patients with SJS/TEN treated with similar regimens.     

Use of etanercept to treat toxic epidermal necrolysis in a human immunodeficiency virus-positive patient

Toxic epidermal necrolysis (TEN) is an uncommon and severe cutaneous adverse drug reaction that causes disseminated necrosis of epidermal cells and mucocutaneous detachment. Here, we report the case of a 32-year-old man with human immunodeficiency virus infection who presented with generalized violaceous macules and blister formation 4 days after the administration of mefenamic acid and amoxicillin for a dental procedure. Additional symptoms included oral ulcers and conjunctivitis. Results of skin biopsy were compatible with Stevens–Johnson syndrome (SJS). SJS progressed to TEN within 2 days. Etanercept treatment showed a dramatic improvement in the symptoms of mucocutaneous lesions. To our knowledge, this is the first report on the treatment of TEN using etanercept in a human immunodeficiency virus-positive patient.     

Effects of etanercept treatment on lipid profile in patients with moderate-to-severe chronic plaque psoriasis: a retrospective cohort study

Treatment with tumor necrosis factor alpha (TNF-α) inhibitors may have favourable effects on the lipid profile. This is the first study to assess the impact of etanercept on the lipid profile in patients with moderate-to-severe plaque psoriasis. To investigate the effect of etanercept on the lipid profile after 24 weeks of treatment in patients with moderate-to-severe plaque psoriasis. We conducted a retrospective cohort study reviewing the medical records of 45 consecutive patients who were treated for psoriasis with etanercept between June 2006 and September 2009. Demographic and clinical data were collected. Levels of total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose and C-reactive protein were recorded at the start of etanercept and at week 24. Levels of total cholesterol, LDL-C and triglycerides increased after 24 weeks of treatment with etanercept, with mean differences of 7.1 mg/dL (p=0.505), 2.0 mg/dL (p=0.718) and 2.8 mg/dL (p=0.180), respectively. HDL-C decreased, with a mean difference of -1.4 mg/dL (p=0.995). None of these changes were statistically significant. We found no favourable changes on the lipid profile after 24 weeks of treatment with etanercept in responding patients with chronic plaque psoriasis.     

Etanercept for the treatment of refractory pyoderma gangrenosum: a brief series

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerative inflammatory condition of unknown etiology. Therapy for PG involves local wound care along with topical and systemic anti-inflammatory and other immunodulatory agents. Etanercept is one such immunomodulator with activity against the inflammatory cytokine, tumor necrosis factor. OBJECTIVE: To evaluate the efficacy and safety of etanercept in the treatment of PG ulcers. METHODS: A retrospective analysis was performed on seven patients with 11 refractory PG ulcers treated with subcutaneous injections of etanercept (25-50 mg twice weekly). RESULTS: All seven patients with PG responded well to etanercept. Eight of the 11 ulcers (73%) completely healed with the mean time of (12.5 weeks), while the other three ulcers had marked reduction in size (within 8-18 weeks). Etanercept was well tolerated. No serious side-effects were reported. Only one patient discontinued the drug secondary to side-effects. CONCLUSION: Etanercept is an alternative treatment option for patients with refractory ulcers due to PG.     

Successful treatment of interstitial lung disease related to Stevens–Johnson syndrome/toxic epidermal necrolysis overlap with etanercept: A case report and published work review

Interstitial lung disease (ILD) is a rare complication of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this study, we present the case of a 33‐year‐old woman who was diagnosed with ILD related to SJS/TEN overlap syndrome. Surprisingly, the patient did not respond to combination therapy with steroids and i.v. immunoglobulin, but rapidly improved after two doses of etanercept treatment. To our knowledge, this is the first case of SJS/TEN‐induced ILD that was successfully treated with etanercept. We reviewed another two cases of ILD associated with SJS/TEN, and found that unlike the other cases, in the present case, ILD occurred early in the course of the disease and rapidly improved after etanercept injection. We discovered that in the present patient, the serum interleukin‐6 level increased during the progressive stage and declined after the initiation of treatment with etanercept.     

The treatment of psoriasis with etanercept

Etanercept is a tumor necrosis factor alpha (TNF-alpha) inhibitor approved for the treatment of psoriasis. Etanercept is a soluble version of the tumor necrosis factor receptor (TNFR) that neutralizes the proinflammatory activity of TNF-alpha, a molecule central to the pathogenesis of psoriasis. Patients receiving etanercept continuously during both 12 and 24 weeks show a significant reduction in the signs of psoriasis. Further, higher doses of etanercept provide better efficacy. Both clinical trial and postmarketing experience with etanercept is extensive and, thus, etanercept has a well-defined safety and tolerability profile. With appropriate patient selection and follow-up, etanercept therapy has a very good benefit-to-risk ratio and represents a convenient option for patients with moderate-to-severe psoriasis.     

Low-dose etanercept therapy in moderate to severe psoriasis in Korean

Etanercept is a fully humanized soluble tumor necrosis factor (TNF)-alpha receptor that competitively inhibits the interaction of TNF-alpha with cell-surface receptors. It was approved as monotherapy for psoriasis in the USA in 2004, but in Korea, no clinical reports on its use for psoriasis are available. We performed a retrospective analysis of 26 moderate-to-severe psoriasis patients who had been treated with etanercept. Patients received twice-weekly injections of 25 mg etanercept s.c. for at least 4 weeks. When the patients achieved a 50% reduction of the psoriasis area severity index (PASI 50) they received once-weekly injections, then biweekly injections were provided for maintenance. Patients were evaluated biweekly by clinical photographs and PASI scoring. Treatment efficacy was as follows. A PASI 75 was achieved in 14 patients (54%) and the mean number of injections before achieving a PASI 75 was 10 +/- 7.5. Patients whose initial PASI was less than 10 (iPASI < 10) showed an earlier response (2.6 +/- 1.3 weeks) and a higher PASI 75 rate (63%), than with iPASI > or = 10 (6.9 +/- 4.5 weeks, 50%). Eight patients (31%) received additional phototherapy or systemic therapy because of insufficient responses or for faster improvements and they were excluded in the efficacy evaluation. Adverse events were observed in eight patients (31%), but were not serious. This is the first report on the effectiveness of low-dose etanercept regimen on Asian psoriasis patients. Results in this study showed that low-dose etanercept therapy is effective for moderate-to-severe Asian psoriasis patients, and it may be a valuable treatment option even for relatively moderate psoriasis patients not responsive to conventional treatment. In addition, the medical cost was relatively low compared to that of the standard regimen for white patients.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的临床疗效观察

【摘要】 目的 评价重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR：Fc）治疗由药物引起的中毒性表皮坏死松解症（TEN）的疗效及安全性。方法 2009—2018年于苏州大学附属第二医院等8个中心纳入22例TEN患者，男10例、女12例，年龄22 ~ 75岁。采用rhTNFR：Fc 25 mg/次皮下注射治疗，首剂加倍，每3天1次，连续治疗6 ~ 8次。治疗前及治疗后第4、7、10、13、16、19、22、25天评估患者药疹面积和严重程度指数（DASI）评分、DASI改善指数（DASI50、DASI75、DASI90）；微量样本多指标流式蛋白定量技术检测外周血及疱液TNF-α水平。治疗过程中监测患者体温、皮疹变化及肝肾功能，记录不良事件。统计分析采用重复测量方差分析、配对t检验及Pearson相关分析。结果 22例患者中，未合并感染的20例在首次治疗后24 ~ 72 h体温停止升高，48 ~ 120 h恢复正常。22例首次治疗后24 ~ 48 h控制水疱新发，48 ~ 96 h皮肤颜色由鲜红色转为暗紫色，2周后皮损基本恢复正常。治疗2 ~ 4周，19例肝功能异常患者丙氨酸转氨酶及天冬氨酸转氨酶水平恢复正常。治疗4 ~ 13 d，7例肾功能异常者肌酐、尿素氮得到控制。治疗过程中，22例患者DASI评分逐渐下降（F = 532.81，P＜0.01），从治疗前53.64 ± 8.67降至治疗25 d时的2.05 ± 1.21（t = 26.60，P < 0.001）。治疗第10天，22例（100%）改善达DASI50；治疗第19天，22例（100%）改善达DASI75；治疗第25天，20例（90.90%）改善达DASI90。22例患者外周血TNF-α水平随治疗时间的延长逐渐降低，从治疗前（33.95 ± 27.90） ng/L降至第25天时（2.38 ± 0.79） ng/L。治疗前15例患者疱液TNF-α水平为（111.99 ± 99.41） ng/L，疱液/外周血TNF-α比值1.83 ~ 28.21。治疗前，22例患者血清TNF-α水平与DASI评分无明显相关性（P = 0.10），15例患者疱液TNF-α水平与DASI评分呈正相关（r = 0.59，P = 0.02）。治疗过程中未发现各种急性不良反应。22例患者均完成治疗并痊愈出院，出院后随访6个月未见复发及各种并发症。结论 rhTNFR：Fc是治疗由药物引起的TEN有效及安全的药物。     

Stevens‐Johnson syndrome and toxic epidermal necrolysis‐like cutaneous presentation of chikungunya fever: A case series

Chikungunya fever is a benign, self‐limiting, acute viral illness. An epidemic occurred in New Delhi, India, in August and September 2016. We observed many cases with atypical cutaneous features mimicking Stevens‐Johnson syndrome and toxic epidermal necrolysis during this epidemic, especially in infants and children. Twenty‐one children (13 [61.9%] boys, 8 [38%] girls) presenting with vesico‐bullous and necrotic lesions were reviewed. Cutaneous presentation included vesicles and bullae with purpuric macules and necrosis, seen in 16 (76%) patients. Skin lesions resolved in 5‐7 days, leaving behind hyperpigmentation in seven (33.3%) patients and hypopigmentation in three (14.2%). Minor oral erosions were observed in three (14.2%) patients, and palmoplantar erythema was seen in four (19.04%). It is essential for dermatologists to understand the Stevens‐Johnson syndrome and toxic epidermal necrolysis‐like presentation of chikungunya and not to misinterpret it as true Stevens‐Johnson syndrome and toxic epidermal necrolysis, which will lead to unnecessary intervention and management.