对比关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对脊柱关节炎和类风湿关节炎膝关节炎的疗效

目的 比较单次膝关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)对脊柱关节炎(SpA)和类风湿关节炎(RA)膝关节炎的疗效差异.方法 入选确诊SpA或RA并伴有至少一侧膝关节肿胀及积液的受试者,X线显示该膝关节无变形、中重度骨破坏及关节间隙明显狭窄,入组前经过常规剂量改善病情抗风湿药(DMARDs)治疗至少6周,于目标膝关节腔穿刺,吸净滑液后注射1次25 mg rhTNFR:Fc.在注射4周后评价疗效和不良事件,主要疗效指标为改良(纽约)特种外科医院(HSS)膝关节评分.采用配对t检验,两样本t检验和秩和检验进行统计学分析.结果 27例SpA和15例RA受试者入选并完成研究.SpA组改良HSS膝关节评分基线值为(66±14)分,注射4周后为(86±11)分,治疗前后比较差异有统计学意义(P＜0.05)；RA组基线值为(64±13)分,注射4周后为(80±9)分,治疗前后比较差异有统计学意义(P＜0.05).SpA组的改良HSS膝关节评分改善率为24.2％(16.5％～41.9％),RA组为22.2％(15.3％～37.7％),2组比较差异无统计学意义(P＞0.05).SpA组膝关节滑膜厚度改善率为31.8％(9.3％～57.3％),RA组为1.5％(-19.3％～25.5％),2组比较差异有统计学意义(P＜0.05).SpA组6例、RA组2例发生了不良事件,无严重不良事件发生.结论 单次膝关节腔内注射rhTN FR:Fc对SpA和RA膝关节炎安全有效,且SpA膝关节滑膜厚度的减轻程度要大于RA膝关节.     

肿瘤坏死因子受体-Fc融合蛋白治疗类风湿关节炎与强直性脊柱炎短期疗效及不良反应的差异

目的 观察重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白[rhTNFR:Fc,益赛普(etanercept)]治疗类风湿关节炎(RA)及强直性脊柱炎(AS)的疗效及不良反应,评估其在不同关节病中的作用.方法 对18例难治性RA和22例难治性AS患者,使用ATNFR:Fc 25 mg/次,每周2次皮下注射,持续3个月.在治疗前和治疗后2、4、12周进行疗效及不良反应评估.RA组和AS组疗效评价分别采用美国风湿病学会(ACR20)H和ASAS20疗效评价标准.结果 ①rhTNFR:Fc治疗后As组达到ASAS20的总体有效率为95.5%,而RA组达到ACR20为50%,组间比较差异有统计学意义(P＜0.01);②AS组在rhTNFR:Fc治疗第2、4、12周时达到ASAS20疗效的患者分别为12例、21例和21例,而RA组达到ACR20疗效的为3例、5例和9例,各时段组间比较差异有统计学意义(P＜0.01);③RA组发生不良反应的患者占50%,显著高于AS组的9%(P＜0.01).RA组因无效及不良反应停药的患者5例,而AS组仅1例,脱漏率差异有统计学意义(P＜0.05),AS组的依从性好于RA组;④两组治疗前与治疗后12周X线比较均无明显改变.结论 相对RA患者总体反应而言,AS组患者对rhTNFR:Fc治疗起效快,有效率高,不良反应少,依从性好:但两组治疗前后关节X线均无明显改变.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对类风湿关节炎患者血清IgM- IgG-和IgA-类风湿因子的影响

目的 观察重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc,商品名益赛普)对类风湿关节炎(RA)患者IgM-类风湿因子(RF),IgG-RF,IgA-RF的影响,探讨rhTNFR:Fc治疗RA的免疫学机制.方法 选择华中科技大学同济医学院附属协和医院及武汉市中心医院2007-2008年110例RA患者,采用随机数字表法随机分为rhTNFR:Fc组和甲氨蝶呤组.rhTNFR:Fc组55例,每周2次皮下注射rhTNFR:Fc(25 mg/次),24周.甲氨蝶呤组55例,每周1次口服甲氨蝶呤片,7.5mg/次起,8周内逐步加到15 mg/次,24周.观察药物对IgM-RF、IgG-RF、IgA-RF的影响,临床疗效评价采用28个关节疾病活动度(DAS28)疗效评定标准.组内治疗前后的差异采用配对t检验分析,组间治疗前后的差异采用两样本t检验分析.结果 ①2组患者病情均明显改善,rhTNFR:Fc的IgM-RF降低时间早于甲氨蝶呤组(P＜0.05).②rhTNFR:Fc组血清IgM-RF (29±16) U/ml明显降低(P＜0.05),IgG-RF (145±20) U/ml和IgA-RF(153±34)U/ml明显升高(P＜0.05).③甲氨蝶呤组IgM-RF (44±14) U/ml,IgG-RF (62±14) U/ml和IgA-RF (66±19) U/ml均明显降低(P＜0.05).④对临床指标的分析表明rhTNFR:Fc治疗RA疗效确切.结论 rhTNFR:Fc与甲氨蝶呤均能有效缓解RA的病情.rhTNFR:Fc能显著降低RA患者血清中IgM-RF的水平,而对IgG-RF,IgA-RF水平有升高作用,可能与其治疗RA的免疫学机制有关.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗强直性脊柱炎的多中心双盲随机对照临床研究

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)治疗活动性强直性脊柱炎(AS)的临床疗效和安全性.方法 本研究前6周为随机、双盲、安慰剂对照临床试验,后6周为开放研究.143例活动性AS患者随机接受6周的每周2次rhTNFR:Fc(25 mg)或安慰剂皮下注射,主要疗效指标为达到ASAS20的患者比例,次要疗效指标包括达到临床显效的患者比例,与基线值相比Bath AS疾病活动指数、Bath AS功能指数、Bath AS测量指数、脊柱痛、夜间痛、脊柱炎症、患者总体评估指数、肌腱端指数、关节肿胀指数改善的状况.结果 rhTNFR:Fc治疗可使患者获得显著改善,6周时68%患者达到治疗反应,而安慰剂组仅28%(P＜0.001);其他各项疗效指标在治疗组也有明显的改善.rhTNFR:Fc耐受性好,最常见的治疗相关的不良反应为注射部位皮肤反应.结论 rhTNFR:Fc的安全性和耐受性好,能迅速减轻AS的症状和体征,控制AS患者的病情活动.     

单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白及联合甲氨蝶呤对胶原诱导性关节炎大鼠关节骨破坏影响的实验研究

目的 通过建立胶原诱导性关节炎(CIA)大鼠模型,评价单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)及其联合甲氨蝶呤在抑制CIA大鼠关节骨破坏方面的作用及机制.方法 利用皮下注射牛Ⅱ型胶原诱导Wistar大鼠发病,建立CIA大鼠模型.将造模成功,炎症评分≥2分的CIA大鼠随机分为生理盐水组(0.4 ml/周,腹腔注射)、甲氨蝶呤治疗组(1 mg周,腹腔注射)、rhTN FR:Fc治疗组(0.8 mg,每周2次,腹腔注射)、甲氨蝶呤+rhTN FR:Fc治疗组(甲氨蝶呤1 mg/周+rhTNFR:Fc 0.8mg,每周2次,腹腔注射).治疗8周后,处死大鼠,取踝关节拍摄X线片,胫骨上段行微计算机断层扫描技术扫描和制作硬组织切片,观察各组踝关节骨破坏情况,评价胫骨上段骨小梁变化及骨量变化.统计学处理采用SNK-q检验.结果 治疗8周后,rhTN FR:Fc组,甲氨蝶呤+rhTNFR:Fc组骨小梁面积百分数[(29.1±0.3)％,(26.7±0.6)％]及骨小梁数量(4.4±0.5)/mm,( 4.0±0.6 )/mm]明显高于0.9％氯化钠注射液组和甲氨蝶呤组[(12.9±0.5)％,( 13.2±0.4)％与(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01);rhTNFR:Fc组、甲氨蝶呤+rhTNFR:Fc组骨小梁分离度明显小于0.9％氯化钠注射液组和甲氨蝶呤组(P＜0.01).结论 单用rhTNFR:Fc及联合甲氨蝶呤均具有明显抑制关节骨破坏的作用,且其抑制炎症关节周围骨量减少的作用与抑制局部骨小梁数量减少及骨小梁分离度的增大相关.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎双盲随机多中心对照临床研究

目的研究注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白[rhTNFR：Fc,益赛普,（etanercept）]对活动性类风湿关节炎（RA）患者的疗效及安全性.方法238例患者随机分为试验组和对照组.试验组每周1次口服空白模拟甲氨蝶呤（MTX）,同时接受rhTNFR：Fc皮下注射治疗,每周2次,每次25 mg;对照组每周1次口服定量MTX（每周7.5 mg起,8周内增至15 mg）,同时每周2次皮下注射空白模拟rhTNFR：Fc.疗程24周.疗效评价采用美国风湿病学会（ACR）疗效评定标准.结果治疗2周后,rhTNFR：Fc组ACR20有效率为35.59%,MTX组为22.50%,组间比较差异有统计学意义（P＜0.05）.治疗8周后,rhTNFR：Fc组和MTX组的ACR20、ACR50和ACR70组间比较差异均有统计学意义（（P＜0.05）.治疗12周后,rhTNFR：Fc组ACR20有效率为66.10%,MTX组是51.67%,两组间比较差异有统计学意义（（P＜0.05）.治疗24周后,rhTNFR：Fc组ACR20有效率为75.42%,且ACR70有效率优于MTX组（（P＜0.05）,显示rhTNFR：Fc疗效强于MTX.两组药物之间总的不良反应发生率差异无统计学意义.结论rhTNFR：Fc用于治疗中、重度RA具有良好的安全性和显著的疗效;在前12周治疗期间,rhTNFR：Fc较MTX起效快、效果更明显.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对炎性关节炎患者关节置换术后恢复的影响

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)对炎性关节炎患者关节置换术后恢复的影响.方法 回顾分析67例应用rhTNFR:Fc或传统改变病情抗风湿药(DMARDs)治疗的炎性关节炎患者行关节置换术后伤口感染发生例数、伤口愈合时间、炎症期时间(体温≥37.5 ℃)及抗生素应用时间.根据所应用药物分为rhTNFR:Fc组和传统DMARDs组.其中,rhTNFR:Fc组单用rhTNFR:Fc或rhTNFR:Fc联合传统DMARDs;传统DMARDs组单用或联合应用2种或2种以上传统DMARDs.统计学处理根据数据类型选择t检验或非参数检验.结果 67例患者中,rhTNFR:Fc组18例,传统DMARDs组49例.rhTNFR:Fc组1例出现伤口感染,传统DMARDs组0例,差异无统计学意义(P＞0.05).rhTNFR:Fc组炎症期时间为(4±3) d,传统DMARDs组为(3±3)d,差异无统计学意义(P＞0.05).rhTNFR:Fc组伤口愈合时间为(14.0±3.1)d,传统DMARDs组为(14.7±2.9)d,差异无统计学意义(P＞0.05).rhTNFR:Fc组术后抗生素应用时间为(14.8±9.3)d,传统DMARDs组为(10.3±2.7)d,差异有统计学意义(P＜0.05).结论 炎性关节炎患者围手术期应用rhTNFR:Fc不增加关节置换术后伤口感染发生率,不延长伤口愈合时间及炎症期时间.

Abstract：

Objective To investigate the affect of rhTNFR:Fc on the postoperative recovery of patients with inflammatory arthritis after arthroplasty. Methods Patients with inflammatory arthritis undergoing arthroplasty were included and divided into rhTNFR:Fc group (rhTNFR:Fc only or combined with conven-tional DMARDs) and conventional DMARDs group (monotherapy with or combination of conventional DMARDs). We retrospectively analyzed the incidence of postoperative infection, wound healing time, the febrile period (body temperature ≥37.5 ℃) and the duration of antibiotics treatment after arthroplasty. x2 test and t test were used for statistical analysis. Results Sixty-seven patients were included, 18 in the rhTNFR: Fc group and 49 in the conventional DMARDs group. One postoperative infection occurred in rhTNFR :Fc group but none in the DMARDs group. There was no significant difference by Fisher's exact test (P＞0.05). The febrile duration was (4±3) days in the rhTNFR :Fc group and (3±3) days in the conventional DMARDs group, the difference was not statistically significant (P＞0.05). The wound healing time was (14.0±3.1) days in the rhTNFR :Fc group and (14.7±2.9) days in the conventional DMARDs group, which was not statistically different(P＞0.05). The duration of antibiotics treatment after operation was (14.8±9.3) days in the rhTNFR: Fc group and (10.3±2.7) days in the conventional DMARDs group, the difference was statistically significant (P＜0.05). Conclusion Using rhTNFR:Fc during perioperative period in patients with inflammatory arthritis does not increase the risk of infectious complications or extending wound healing time and the febrile duration.     

肿瘤坏死因子-α拮抗剂治疗中国汉族人群强直性脊柱炎369例不良反应初步研究

目的 旨在评价接受了肿瘤坏死因子(TNF)-α拮抗剂治疗的中国汉族人群强直性脊柱炎(AS)患者的不良反应,为生物制剂的临床治疗提供参考依据.方法 本研究纳入在我科接受了TNF-α拮抗剂治疗的369例中国汉族人群AS患者,未完全跟踪随访给药1011次.所有患者均评估了用药后2h出现的不良反应,对其中126例长期用药患者进行了第8、12、52、104周的随访.观察患者用药后2h的短期不良反应和长期不良反应.采用Fisher确切概率法进行统计分析.结果 接受TNF-α拮抗剂治疗的369例AS患者,随访用药后2h共计发生30次不良反应.英夫利西单抗和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)引起的短期不良反应发生率差异无统计学意义(分别为3.8％,2.6％,P=0.31).126例患者分别依次进行了第8、12、52、104周的随访,共计39例发生不良反应,长期应用英夫利西单抗和rhTNFR:Fc不良反应发生率差异无统计学意义(分别为49％,51％,P=0.69).结论 中国汉族人群AS患者在接受TNF-α拮抗剂治疗时应注意上述不良反应的发生,尤其应注意第3、4次接受英夫利西单抗治疗患者的不良反应.接受英夫利西单抗和rhTN FR:Fc治疗的患者用药后2h内和长期(≥2年)治疗的不良反应发生相当.     

CT引导下骶髂关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗强直性脊柱炎的研究

目的 通过对骶髂关节局部注射重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白(rhTNFR:Fc)的病理及影像研究,初步评价局部生物制剂治疗的临床疗效和安全性.方法 16例强直性脊柱炎(AS)患者采用单侧骶髂关节腔内注射rhTNFR:Fc的局部治疗方法(每月1次,25 mg/次,共3次,总疗程8周),对比20例全身皮下注射用药组(每周2次,25 mg/次,共16次,总疗程8周),分析其疗效、安全性、耐受性.同时观察注药前后骶髂活检组织细胞因子TNF-α、转化生长因子(TGF)-β、白细胞介素(IL)-6 mRNA的表达和光镜、免疫组织化学的变化,以及单光子发射计算机断层(SPECT)和磁共振成像(MRI)在代谢和宏观形态学上的改变.采用t检验或t'检验及χ2 Fisher's 精确检验或秩和检验.结果 rhTNFR:Fc局部注射显示:①治疗组在12周后Bath强直性脊柱炎疾病活动指数(BASDAI)评分(32±13)mm、疲乏(40±16)mm、晨僵(35±16)min、骶髂关节局部压痛(34±22)mm、患者总体评价VAS评分(40±17)mm上有明显改善(P<0.01),不良反应减少,并能节省医疗费用.②治疗后活检组织TNF-α、TGF-βmRNA相对表达量(0.891±0.06,0.84±0.05)较治疗前(1.08±0.19,1.13±0.33)明显下降(P<0.05),IL-6 mRNA相对表达量无明显改变(P>0.05).光镜下表现的滑膜炎、附着点炎、软骨变性、软骨下骨板破坏、骨髓炎的阳性率有所下降,而炎症细胞指数明显下降(z=-2.71,P<0.05).③治疗后骶髂关节放射学核素(ROI)的平均值(1.38±0.16)较治疗前(1.45±0.14)明显减少(P<0.05),MRI上的骨髓水肿、脂肪沉积等改变明显减轻(P<0.05).结论 骶髂关节腔注射rhTNFR:Fc,具有良好的疗效、安全性、耐受性及疗效经济学价值,特别有益于病变早期或局限于骶髂关节病变、不能耐受全身使用生物制剂的AS患者,临床推广应用前景.     

rhTNFR:Fc对类风湿关节炎患者血清中致炎及抗炎性细胞因子的影响

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，益赛普（etanercept）]治疗类风湿关节炎（RA）的免疫学机制，了解rhTNFR：Fc对RA患者血清中致炎及抗炎性细胞因子的作用，比较rhTNFR：Fc和甲氨蝶呤（MTX）对这些细胞因子作用的不同，为rhTNFR：Fc治疗RA提供进一步的实验依据。方法采用酶联免疫吸附试验（ELISA）检测RA患者rhTNFR：Fc治疗前后血清中白细胞介素（IL）-1、IL-6、IL-1、肿瘤坏死因子（TNF）-α和干扰素ONF）-γ度。观察rhTNFR：Fc对细胞因子的影响。结果①RA患者血清中的炎性细胞因子TNF-α、INF-γ、IL-1β、IL-6的水平均高于健康对照组，其中IL-6、INF-γ、TNF-α的水平与健康对照组相比差异有统计学意义（P〈0．01），抗炎性细胞因子IL-10的水平低于健康对照组，但两者相比差异无统计学意义（P〉0．05）。②rhTNFR：Fc治疗RA后血清中Th1型细胞因子TNF-α、INF-γ、IL-1β、IL-6水平均明显降低（P〈0．01），而Th2型细胞因子IL-10的水平明显提高（P〈0．01）。③RA患者血清中TNF-α水平与肿胀关节数及肿胀关节指数呈正相关（P〈0．05）。④对临床指标的分析表明，rhTNFR：Fc治疗RA疗效确切。结论rhTNFR：Fc可以降低RA患者血清中TNF-α、INF-γ、IL-1β、IL-6的水平，同时升高IL-10水平；在抑制了Th1型细胞因子的同时．增强了Th2型细胞因子的效应．从而改善RA的病情。     

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活动性类风湿关节炎的疗效和安全性的开放多中心临床研究

目的 评估重组人Ⅱ型肿瘤坏死因子受体—抗体融合蛋白(rhTNRF:Fc)联合甲氨蝶呤治疗活动性类风湿关节炎(RA) 52周的临床疗效、放射学改变和安全性。方法 30例中重度活动性RA患者应用rhTNRF：Fc(25 mg皮下注射,每周2次)联合甲氨蝶呤（每周15 mg口服）治疗。应用美国风湿病学会(ACR)20、50、70疗效标准和28个关节的疾病活动度评分(DAS28)评估临床疗效,应用改良的Sharp评分标准评价放射学疗效。计数资料应用x2检验或Fisher精确检验,计量资料采用配对t检验。结果 治疗52周时达到ACR20、50、70标准的有效率分别为90％、87％和67％。DAS28由6.4±0.6降至3.4±1.1(P＜0.01),23％患者达到疾病缓解,17％达到低度活动状态。健康状况问卷由1.18±0.56降至0.25±0.34（P＜0.01）。基线期和52周时,双手和双腕X线片关节间隙狭窄（8±10与8±11）和关节侵蚀(10±15与10±15)的改良Sharp评分差异无统计学意义;73％患者无放射学进展。未见严重不良反应,无新发结核菌感染和恶性肿瘤。结论 rhTNRF:Fc联合甲氨蝶呤治疗RA 52周能够显著减低疾病活动度、改善关节功能以及延缓放射学进展,达到临床缓解和阻止放射学进展的治疗目标：且耐受性良好。     

A comparison study of a recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) and methotrexate in treatment of patients with active rheumatoid arthritis in China

The objective of this study is to evaluate the efficacy and safety of rhTNFR:Fc: a recombinant tumor necrosis factor receptor:Fc fusion protein compared with methotrexate (MTX) in patients with rheumatoid arthritis in China. We treated 238 patients with active rheumatoid arthritis with either twice weekly subcutaneous injection rhTNFR:Fc (25 mg) or weekly oral MTX (mean 15 mg per week) for 24 weeks (registration number: 2003L01264). Clinical responses were defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR-N). As compared with MTX-treated patients, more patients who received rhTNFR:Fc had ACR20 improvement in disease activity during the first 2 weeks (P < 0.05). Similarly, more patients treated with rhTNFR:Fc having ACR20, ACR50, ACR70 improvement in disease activity during 8 weeks (P < 0.05). At the end of 12-week treatment, patients received rhTNFR:Fc also had significant improvement at ACR20 (P < 0.05). Compared with oral MTX, patients received rhTNFR:Fc also had significant improvement at ACR70 at the end of 24 weeks treatment (P < 0.05). In conclusion, compared with oral MTX subcutaneous injection, rhTNFR:Fc acted more rapidly to release symptoms and signs of active RA in Chinese patients, and well tolerated in patients with rheumatoid arthritis in China.     

肿瘤坏死因子拮抗剂治疗风湿性疾病安全性的短期临床观察

目的 描述肿瘤坏死因子(TNF)-α拮抗剂治疗风湿性疾病发生的不良反应,评价临床应用的安全性和耐受性.方法 对2007年1月至2008年10月使用TNF-α拮抗剂的患者从临床症状、体征及实验室检查方面记录使用过程中发生的不良反应及程度和最终结局.结果 78例患者中35%(27/78)为类风湿关节炎(RA),41%(32/78)为强直性脊柱炎(AS),17%(13/78)为银屑病关节炎(PsA),6%(5/78)为未分化脊柱关节病(uSpA).59例患者使用依那西普,7例(12%)发生注射局部反应、上呼吸道感染及结核病等不良反应.19例患者使用英夫利西单抗,3例(16%)发生不良反应,1例(AS)为上呼吸道感染,1例(AS)前两次均在输注完24 h内出现伞身红色丘疹及心悸,1例(RA)输注4次后出现不明原因发热.部分不良反应可自行消失,其余经适当处理后痊愈.结论 证实依那西普和英夫利西单抗治疗风湿性疾病具有较好的安全性和耐受性,发生的不良反应是温和的,经适当处理可痊愈.     

Experience with anti‐tumor necrosis factor‐α therapy in India

Aims: To review the Indian experience with anti‐tumor necrosis factor (TNF)‐α therapy. Methods: ‘PubMed’ and ‘IndMED’ were searched for Indian studies on anti‐TNF‐α therapy. Data were compiled and analysed. Results: Data on infliximab from 176 patients from five different series were collated. One hundred and forty‐seven had ankylosing spondylitis (AS), nine had polyarticular juvenile idiopathic arthritis (JIA), 12 had rheumatoid arthritis (RA), six had undifferentiated spondyloarthropathy, one had inflammatory bowel disease‐related spondyloarthritis and one had psoriatic arthritis. Thus, 155/176. (88%) had spondyloarthropathy (SpA). No screening for latent tuberculosis was done in any of the studies. One series comprising 108 cases of AS, used 3 mg/kg infliximab infusions (instead of 5 mg/kg) at 8‐weekly intervals with omission of the 2‐week and 6‐week doses. All others with SpA (n = 47) followed the standard protocol: 171/176 patients had a significant improvement. Reactivation tuberculosis developed in 5/47 (10.6%) SpA patients treated with standard doses of infliximab. This amounted to 56 times increased risk compared to baseline (0.187%). None of the 129 patients treated with 3 mg/kg infusions of infliximab developed reactivation tuberculosis (AS ?108, RA ?12, JIA ?9). The lone study on etanercept showed good efficacy in 40 patients with RA. However, seven serious adverse events occurred. Conclusions: Infliximab showed expected efficacy in SpA, RA and JIA. Reactivation tuberculosis developed in 10.6% of the SpA group treated with standard regimen. Patients treated with lower doses of infliximab which included a large subgroup of SpA patients and those with RA or JIA did not develop tuberculosis.     

Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and juvenile idiopathic arthritis

TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.