阿达木单抗联合甲氨蝶呤治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究

目的 评价阿达木单抗联合甲氨蝶呤(MTX)治疗类风湿关节炎(RA)的疗效与安全性.方法 随机、双盲、平行、安慰剂对照的多中心临床试验.302例入组前已经至少接受MTX 3个月治疗且剂量稳定≥28 d的活动性RA患者,随机分为40 mg阿达木单抗+MTX组(A组,121例)、80 mg阿达木单抗+MTX组(B组,121例)、安慰剂+MTX组(C组,60例).患者隔周皮下注射阿达木单抗或安慰剂,双盲治疗期为12周.完成双盲期的患者进入后12周开放期,3组患者均予隔周皮下注射40 mg阿达木单抗.在双盲期和开放期的患者同时继续接受研究前稳定剂量的MTX.观察主要疗效指标[双盲期治疗第12周修改的美国风湿病学会疗效标准提高20%(ACR20)有效率]、次要疗效指标[第24周ACR20有效率;第12周、第24周修改的美国风湿病学会疗效标准提高50%(ACR50)、修改的美国风湿病学会疗效标准提高70%(ACR70)有效率]、压痛关节数、肿胀关节数、疼痛视觉模拟评分,医生对疾病活动性整体评价、患者对疾病活动性整体评价、健康评价问卷(HAQ)评分、评估健康相关生活质量简表36(SF-36)评分及不良事件.结果 (1)双盲期,ACR20有效率C组为35.0%,A组为57.0%,B组为51.2%,A组、B组与C组比较,P<0.05;A组ACR50、ACR70有效率分别为32.2%、15.7%,与C组比较,P<0.05;A组压痛关节数、肿胀关节数、C反应蛋白水平的改善优于C组(P<0.05);B组肿胀关节数、C反应蛋白水平的改善优于C组(P<0.05).(2)开放期,A组、B组ACR20、ACR50、ACR70有效率仍维持或有所提高,而C组的ACR20、ACR50、ACR70有效率则升高至与A组、B组类似的水平.在压痛关节数、肿胀关节数、疼痛视觉模拟评分、HAQ、SF-36方面,3组均比基线、第12周时有更明显的好转.(3)双盲期与开放期中超过5%的患者有不良事件(上呼吸道感染、鼻咽炎和注射部位瘙痒),多数为轻～中度.有3例患者在研究期间出现结核病.在双盲期,有3例(1.2%)受试者出现了严重不良事件,但研究者判定与药物无关或可能无关.在开放期,有8例(2.7%)受试者出现了严重不良事件,其中3例判定与药物无关或可能无关.结论 阿达木单抗联合MTX治疗RA的疗效优于单用MTX,可显著提高治疗有效率并持续改善症状、体征、实验室炎性活动指标,减少功能障碍并提高整体生活质量,同时具有良好的安全性与耐受性.     

英利昔单抗联合甲氨蝶呤治疗类风湿关节炎的随机双盲临床研究

目的评价英利昔单抗与甲氨蝶呤(MTX)联合使用与单独使用MTX,在治疗类风湿关节炎(RA)中的疗效与安全性。方法本研究为随机、双盲、平行对照的临床试验。49例接受过至少3个月稳定剂量MTX治疗的活动性RA患者随机分为试验组(24例)和对照组(25例)。两组受试者在第0、2、6、14周分别接受3mg/kg的英利昔单抗或安慰剂静脉滴注,同时每周按固定剂量继续服MTX。并于试验的第0、2、6、14、18周随访,评价疗效和不良反应。以美国风湿病学会(ACR)疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、晨僵时间、关节肿胀数、关节肿胀指数、关节压痛数、关节压痛指数；次要疗效指标为疼痛目视模拟测量表(VAS)评分、疲乏VAS评分、疾病总体状况的医生评价VAS评分、疾病总体状况的病人评价VAS评分、健康评价问卷(HAQ)评分。结果治疗后第2周时,英利昔单抗联合MTX组ACR20有效率为62．5%,对照组仅为8．0%(P=0．002)；晨僵时间、关节压痛数、关节压痛指数、关节肿胀数、关节肿胀指数、疼痛VAS、疲乏VAS、医生总体评价VAS、病人总体评价VAS、HAQ和血沉等较对照组也均有显著的改善(P＜0．05或P＜0．01)。第18周时,英利昔单抗联合MTX组ACR20有效率为79．2%,对照组只有48．0%(P=0．024)。两组之间不良事件发生率差异无统计学意义。结论英利昔单抗联合MTX治疗RA的疗效明显优于单用MTX的疗效,能迅速改善与RA有关的各项症状、体征和实验室炎性活动指标,具有良好的安全性。     

甲氨蝶呤联合环磷酰胺治疗类风湿关节炎随机单盲对照临床研究

目的 评价甲氨蝶呤(MTX)联合环磷酰胺(CTX)及单独应用MTX、单独应用CTX治疗类风湿关节炎(RA)的疗效和安全性.方法 本研究为随机、单盲、对照的临床试验.符合纳入及排除标准的RA患者随机分为单用MTX(10～15 mg/周)、单用CTX(400 mg/2～3周)及MTX联合CTX治疗组(MTX10～15 mg/周+CTX 400 mg/2～3周).疗程24周,在基线、6、12、24周进行疗效及安全性评估.以美国风湿病学会(ACR)疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、欧洲抗风湿联盟(EULAR)疗效指标、疼痛目视模拟测试表(VAS)评分、患者对自身健康状况的总体评估(PGA)、医生总体评价、压痛关节数(TJC)、压痛关节指数(TJI)、肿胀关节数(SJC)、肿胀关节指数(SJI)、健康评估问卷(HAQ)为次要疗效指标.结果 在第24周,MTX+CTX组达ACR20改善的患者比例(81%)高于MTX组(56%)及CTX组(35%),差异有统计学意义(P＜0.05).24周时MTX+CTX组达ACR50改善的患者比例高于CTX组(P＜0.05).与MTX组之间差异无统计学意义(P＞0.05).在第24周,MTX+CTX组达到EULAR有效的患者比例(77%)高于MTX组(48%)及CTX组(35%),差异有统计学意义(P＜0.05).24周时MTX+CTX组在TJC/TJI、SJC/SJI疼痛VAS评分、ESR的改善程度高于MTX组(P＜0.05).在压痛关节数脂数、肿胀关节数/指数、疼痛VAS评分、PGA、医生总体评价、HAQ、ESR的改善程度高于CTX组(P＜0.05).3组之间不良反应发生率差异无统计学意义.结论 MTX联合CTX治疗能显著改善RA的症状、体征和实验室炎性指标,疗效优于单用MTX及单用CTX.两者联合治疗安全耐受性好,与单用MTX及单用CTX相比,并不增加不良反应的发生率.     

利妥昔单抗联合甲氨蝶呤治疗重度类风湿关节炎的随机双盲安慰剂对照的临床研究

目的 观察利妥昔单抗联用甲氨蝶呤(MTX)治疗重度活动性类风湿关节炎(RA)72周后的疗效和安全性.方法 将患者按2:1:1的比例随机分为500 mg利妥者单抗治疗组、1000 mg利妥昔单抗治疗组及安慰剂组,所有患者同时服用MTX 7.5～20 mg/周,每24周为1个疗程,每疗程于第1日和第15 日输注利妥昔单抗500 mg或1000mg或安慰剂.主要疗效指标为达到ACR20的患者比例,次要疗效指标为达到ACR50、ACR70的比例,及DAS28的改善情况.结果 满足方差齐性,则采用单因素方差分析或t检验方法,如不满足方差齐性,则采用秩转换检验方法.结果 共纳入22例DAS28＞5.1的重度RA患者(女性占93%,平均年龄50岁,MTX平均服用剂量17.6 mg/周),有2例患者因疗效不佳退出,其余患者均完成了 4个疗程的利妥昔单抗治疗,症状明显缓解,在72周结束实验时,500 mg利妥昔单抗组达到ACR20的比例为80%,而1000 mg组达到ACR20的比例为60%,安慰剂+MTX组达到ACR20的比例为57%,同时各治疗组患者红细胞沉降率、DAS28均较基线显著下降.最常见的不良反应为上乎吸道感染,其次是淋巴细胞下降及肝功能异常.结论 利妥昔单抗对RA具有显著的疗效和良好的安全性.     

依那西普治疗活动性强直性脊柱炎多中心、双盲、随机对照临床研究

目的 评价依那西普50 mg每周1次治疗活动性强直性脊柱炎(AS)的疗效与安全性.方法 为期12周(双盲期和开放期各6周)的随机、双盲、安慰剂对照的多中心临床研究.双盲治疗期治疗组和对照组受试者分别接受依那西普或安慰剂50 mg,1次/周,皮下注射;开放期均接受依那西普50 mg,1次/周,皮下注射.分别于第0、2、4、6、8、10、12周按规定完成临床评估.主要疗效指标为达到AS疗效评价(ASAS) 20％改善程度(ASAS 20)的受试者比例,次要疗效指标为达到ASAS标准中6项改善5项( ASAS5/6)的受试者比例、达到ASAS部分缓解的受试者比例、Bath强直性脊柱炎疾病活动指数(BASDAI)改善达到50％以上(BASDAI 50)的受试者比例、受试者总体评价、背痛、Bath 强直性脊柱炎功能指数(BASFI).所有受试者均进行安全性评价.结果 来自6个医院的400例受试者入选本研究,其中治疗组300例,对照组100例.381例受试者完成全部治疗,其中治疗组285例,对照组96例.双盲治疗期第2周时治疗组有55.7％的受试者达到ASAS20,对照组为17.0％,差异有统计学意义(P ＜0.001);至第6周时治疗组有77.5％的受试者达到ASAS 20,对照组为32.3％ (P＜0.001).经12周治疗,治疗组89.5％的受试者达到ASAS20.治疗组各次要疗效指标(ASAS5/6、ASAS部分缓解、BASDAI 50等)也有显著改善.最常见的不良反应为注射部位反应、肝酶水平升高,无恶性肿瘤发生,未见死亡.结论 依那西普50 mg每周1次治疗活动性AS,具有使用方便、起效迅速、疗效显著、耐受性良好的特点.     

Infliximab治疗类风湿关节炎的随机双盲平行多中心临床试验

目的评价infliximab与甲氨蝶呤(MTX)联合使用与单独使用MTX在治疗类风湿关节炎(RA)中的疗效与安全性。方法随机、双肓、平行、多中心试验。患者在入组前至少MTX治疗3个月,且MTX剂量稳定在7．5～20 mg/周,病情未得到满意控制。受试者在第0、2、6、14周分别接受3 mg/kg的infliximab或安慰剂静脉滴注,同时每周按同定剂量服MTX。受试者分别在试验的第0、2、6、14、18周随访．评价疗效和不良反应。疗效以美国风湿病学会(ACR)疗效评价指标为指标。其中以ACR20为主要疗效指标,ACR50、ACR70、关节肿胀数、关节肿胀评分、关节触痛数、晨僵持续时间、疼痛视觉模拟评分(VAS)及疲乏VAS评分、C反应蛋白(CRP)、血沉(ESR)、健康状况问卷(HAQ)为次要疗效指标。结果本研究试验组87例、对照组86例。试验第2周时,infliximab MTX组ACR20改善者占52．9％,对照组只有14．0％(P=0．0003)；且关节肿胀数、关节触痛数、晨僵时间、疼痛VAS的评分、CRP、ESR等指标明显改善,有统计学意义(P＜0．05)。第18周,infliximab MTX组ACR20改善者75．9％,对照组只有48．8％(P= 0．0003)：ACR50改善者43．7％、对照组25．6％(P=0．01 1)。与单用MTX对照组相比,其不良事件发生率差异无统计学意义(P=0．215),多数不良事件无需停药,试验组有1例结核感染者。结论Infliximab MTX治疗RA的疗效明显优于单用MTX的疗效,能迅速改善RA的各项症状、体征和实验室炎性活动指标。     

托法替布治疗老年性类风湿关节炎的疗效及安全性

目的观察托法替布在治疗老年性类风湿关节炎(RA)中的疗效和安全性, 为老年患者的治疗提供临床依据。方法随机对照临床试验。选取2019年1月至2021年1月就诊于苏州大学附属第一医院风湿免疫科的老年性RA患者90例, 按照随机数字表法随机分为甲氨蝶呤组(MTX组)和托法替布组(TOF组), 每组45例。MTX组患者主要以MTX每周1次、每次10 mg剂量治疗, TOF组患者主要以托法替布每天2次、每次5 mg剂量治疗, 评估两组患者治疗12周的疗效和安全性。疗效主要终点为第12周时美国风湿病学会(ACR)定义的疾病缓解50%(ACR50)的应答率。次要终点包括第12周的ACR20/70应答率、达标治疗患者的比例[评估方法包括基于红细胞沉降率(ESR)的28个关节的疾病活动性评分(DAS28-ESR)、基于C反应蛋白(CRP)的28个关节的疾病活动性评分(DAS28-CRP)、临床疾病活动指数(CDAI)和简化的疾病活动指数(SDAI)]以及患者报告结局(PRO)[包括疼痛视觉模拟标尺评分(VAS)和健康评估问卷残疾指数(HAQ-DI)较基线改变情况]。安全性评估指标包括与药物相关的不良事...     

托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究

  目的 评价托珠单抗联合改善病情抗风湿药（DMARDs）治疗DMARDs疗效不佳的活动性中重度类风湿关节炎（RA）患者的有效性与安全性。方法 随机、双盲、安慰剂对照、多中心临床试验。DMARDs疗效不佳的中重度活动性RA患者按2∶1 的比例随机分入托珠单抗组(托珠单抗+DMARDs) 或安慰剂组(安慰剂+DMARDs),每4 周静脉滴注1次托珠单抗8 mg/kg,同时继续应用稳定剂量的DMARDs。完成双盲期的患者可以选择进入为期24周的开放期,接受每4周静脉滴注1次托珠单抗8 mg/kg。主要观察指标：第24周时达到美国风湿病学会（ACR）制定的RA疗效缓解20%（ACR20）、RA疗效缓解50%（ACR50）、RA疗效缓解70%（ACR70）的受试者比例;达到28个关节疾病活动指数（DAS）≤3.2、DAS28<2.6的受试者比例。结果 （1）托珠单抗组139例、安慰剂组69例患者完成了24周的双盲期临床观察,达到ACR20、ACR50和ACR70的受试者比例托珠单抗组（69.8%、38.8%、12.9%）显著高于安慰剂组（24.6%、10.1%、2.9%,P<0.05)。托珠单抗组患者红细胞沉降率、C反应蛋白、血红蛋白、DAS28≤3.2及DAS28<2.6的受试者比例的改善优于安慰剂组。托珠单抗组患者治疗后Ⅰ型胶原羧基端吡啶并啉交联肽、ⅡA型前胶原氨基端前肽、基质金属蛋白酶-3水平下降。（2）48周开放期共有202例RA患者接受了托珠单抗治疗,达到ACR20、ACR50、ACR70的受试者比例分别为81.2%、60.4%、36.6%。DAS28降至2.760±1.402,50.5%的患者达到DAS28<2.6。（3）托珠单抗组发生59例（42.4%）不良事件,高于安慰剂组（27.9%）。严重不良事件发生率托珠单抗组为0.7%,安慰剂组为5.9%。最常见的不良事件为感染,绝大多数为轻中度。托珠单抗组患者出现丙氨酸转氨酶和天冬氨酸转氨酶显著升高;总胆固醇、低密度脂蛋白、高密度脂蛋白和甘油三酯水平升高,但未观察到心血管事件的增加。治疗48周时未出现新的不良事件。结论托珠单抗联合DMARDs治疗DMARDs疗效不佳的中重度活动性RA患者有显著临床疗效,患者安全性与耐受性良好。        

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.     

强直性脊柱炎患者外周血T淋巴细胞亚群和T淋巴细胞上CD154表达的变化和意义

目的 探讨强直性脊柱炎(AS)患者外周血T淋巴细胞亚群分布和T淋巴细胞上共刺激分子CD154的表达及依那西普治疗对其的影响.方法 用流式细胞仪检测66例AS患者(其中活动期39例,非活动期27例;按临床特征分为外周关节和中轴均受累者35例和单独中轴受累31例)、30例类风湿关节炎(RA)患者及30名健康志愿者外周血T淋巴细胞亚群分布和CD154在CD3+T淋巴细胞上的表达.此外,观察39例AS活动期患者在随机双盲依那西普和安慰剂对照试验中,用药前后CD154的变化.结果 ①AS和RA患者CD4+T淋巴细胞均较健康志愿者高(P＜0.05),而CD8+T淋巴细胞较健康志愿者低(P＜0.05);AS患者外周血T细胞上CD154的表达较健康志愿者和RA患者都明显升高(P＜0.05);②活动期或外周关节受累AS患者T细胞CD154的表达分别较稳定期或单独中轴受累AS患者明显升高(P＜0.05);且CD154的表达与关节压痛数、关节肿胀数呈正相关(P＜0.05);③在依那西普试验的第6周,依那西普组AS患者(19例)T淋巴细胞CD154表达较安慰剂组(20例)明显下降(P＜0.05),与健康志愿者差异无统计学意义(P＞0.05).结论 AS患者外周血存在T淋巴细胞亚群紊乱和T淋巴细胞上共刺激分子CD154异常表达,可作为临床评价AS病情活动性和依那西普疗效的生物指标之一.     

Efficacy and safety of etanercept 50 mg twice a week in patients with rheumatoid arthritis who had a suboptimal response to etanercept 50 mg once a week: results of a multicenter, randomized, double-blind, active drug-controlled study

OBJECTIVE: To evaluate the efficacy and safety of treatment with 50 mg of etanercept twice a week plus weekly methotrexate (MTX; > or =15 mg) in patients with rheumatoid arthritis (RA) who had a suboptimal response to 50 mg of etanercept once a week plus weekly MTX (> or =15 mg). METHODS: In this multicenter, randomized, double-blind, active drug-controlled study, suboptimal responders to treatment with MTX plus etanercept 50 mg once weekly were given MTX plus etanercept 50 mg twice weekly (n = 160) or MTX plus etanercept 50 mg once weekly plus a placebo (n = 40) for 12 weeks. In a subsequent 12-week open-label period, patients who responded to etanercept 50 mg twice weekly decreased their dosage to 50 mg once weekly, those who had a partial response to etanercept 50 mg once weekly increased their dosage to 50 mg twice weekly, and those who had no response to etanercept 50 mg twice weekly were discontinued. The primary end point was the proportion of patients with a response on the Disease Activity Score 28-joint assessment (DAS28) at week 12. RESULTS: A total of 201 patients were randomized; 187 completed 12 weeks, and 102 completed 24 weeks. At week 12 (double-blind period), the DAS28 response in the 50 mg twice weekly and the 50 mg once weekly groups was not significantly different (45.6% versus 35.0%; P = 0.285), and similar proportions of patients in the groups taking 100 mg and 50 mg experienced adverse events (34.4% versus 37.5%; P = 0.711). Serious adverse events occurred in 7 of 160 of the 50 mg twice weekly group and 0 of 40 of the 50 mg once weekly group (P = 0.387), and serious infectious events occurred in 3 of 160 patients in the 50 mg twice weekly group (P = 0.884). CONCLUSION: Etanercept 50 mg once weekly is an optimal dosage in most patients with RA. Increasing the dosage from 50 mg once weekly to 50 mg twice weekly in suboptimal responders did not significantly improve their DAS28 responses.     

Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA). METHODS: Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8. RESULTS: An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg etanercept once weekly, by 49% of the patients receiving 25 mg etanercept twice weekly, and by 19% of the patients in the placebo group (P 相似文献   

Once‐weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: Results of a multicenter,randomized, double‐blind,placebo‐controlled trial

Objective

To evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA).

Methods

Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8.

Results

An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg etanercept once weekly, by 49% of the patients receiving 25 mg etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 etanercept groups.

Conclusion

Safety, efficacy, and pharmacokinetics were comparable between the 2 etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.

     

Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial

OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX). METHODS: In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adalimumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P < or = 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P < or = 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the patients receiving 40 mg every other week. CONCLUSION: In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX.     

Anti-tumor necrosis factor therapy does not diminish the immune response to influenza vaccine in Japanese patients with rheumatoid arthritis

Abstract

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6–8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.     

Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis

OBJECTIVE: To compare the efficacy, pharmacokinetics and safety of etanercept 50 mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing spondylitis. METHODS: A 12-week, double-blind, placebo-controlled study compared the effects of etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo in 356 patients with active ankylosing spondylitis (3:3:1 randomisation, respectively). The primary end point was the proportion of patients achieving a response at week 12 based on the Assessment in Ankylosing Spondylitis Working Group criteria (ASAS 20). The pharmacokinetics of etanercept 50 mg once weekly and 25 mg twice weekly were analysed. RESULTS: Baseline characteristics and disease activity were similar among the three groups: etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo. The percentage of patients discontinuing therapy was 9.0%, 9.3% and 13.7% for the three respective groups. ASAS 20 response at 12 weeks was achieved by 74.2% of patients with etanercept 50 mg once weekly and 71.3% of those with etanercept 25 mg twice weekly, both significantly higher than the percentage of patients taking placebo (37.3%, p<0.001). Percentages of patients with ASAS 5/6 response (70.3%, 72.0% and 27.5%, respectively; p<0.001) and those with ASAS 40 response (58.1%, 53.3% and 21.6%, respectively; p<0.001) followed a similar pattern. Significant improvement (p<0.05) was seen in measures of disease activity, back pain, morning stiffness and C reactive protein levels as early as 2 weeks. Serum etanercept exposure was similar between the etanercept groups. Incidence of treatment-emergent adverse events, including infections, was similar among all three groups, and no unexpected safety issues were identified. CONCLUSIONS: Patients with ankylosing spondylitis can expect a comparable significant improvement in clinical outcomes with similar safety when treated with etanercept 50 mg once weekly or with 25 mg twice weekly.     

Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: An open-label extension of a randomized,double-blind,placebo-controlled trial

Abstract

Objective. To obtain safety and efficacy data on combination treatment with iguratimod and methotrexate (MTX) in an open-label extension study in patients with active rheumatoid arthritis (RA).

Methods. Following a 28-week, randomized, double-blind trial of adding iguratimod or placebo to stable MTX therapy, patients entered a 24-week extension. Patients randomized to the iguratimod + MTX group continued treatment. Patients treated with placebo + MTX switched to iguratimod + MTX [the (placebo/iguratimod) + MTX group].

Results. In the iguratimod + MTX group, the rate of 20% improvement in American College of Rheumatology criteria (ACR20) at week 52 (71.3%) was similar to that at week 24 (69.5%). ACR50, ACR70 and Health Assessment Questionnaire Disability Index at week 52 significantly improved compared with the values at week 24. In the (placebo/iguratimod + MTX) group, the switch to iguratimod treatment significantly improved ACR20 from 30.7% at week 24 to 72.1% at week 52. Frequent adverse events for 52 weeks in the iguratimod + MTX group were nasopharyngitis, upper respiratory tract inflammation, stomatitis, lymphocyte decrease, AST increase, ALT increase and blood iron decrease. These adverse events were predominantly mild or moderate in severity. No deaths occurred.

Conclusion. Efficacy and tolerance of iguratimod + MTX therapy was maintained to 52 weeks in patients with active RA with inadequate response to MTX.     

A phase 3 randomized,double-blind,multicenter comparative study evaluating the effect of etanercept versus methotrexate on radiographic outcomes,disease activity,and safety in Japanese subjects with active rheumatoid arthritis

Abstract

Objectives The aim of this phase 3, double-blind study was to compare the radiographic and clinical effects of etanercept (ETN) versus methotrexate (MTX) over 52 weeks in Japanese subjects with active rheumatoid arthritis.

Methods The study population comprised 550 subjects with inadequate response to ≥1 disease-modifying anti-rheumatic drugs who were randomized to treatment groups of ETN 25 mg twice weekly (BIW; n = 182), ETN 10 mg BIW (n = 192), or MTX (≤8.0 mg/week; n = 176).

Results Of the 550 subjects initially enrolled in the three treatment groups, 21.6 % discontinued the study; a significantly higher proportion of those who withdrew from the study due to lack of efficacy were in the MTX (21.6 %) group compared with the ETN 25 mg (3.3 %) and ETN 10 mg (6.8 %) groups (P < 0.001). Mean change from baseline in the modified total Sharp score at week 52 (primary endpoint) was significantly lower in the ETN 25 mg [3.33; standard error (SE), 0.73] and ETN 10 mg (5.19; SE 0.93) groups than in the MTX group (9.82; SE 1.16; P < 0.0001 vs. either ETN group). Compared with subjects receiving MTX, significantly higher percentages of subjects treated with ETN 25 and 10 mg achieved American College of Rheumatology (ACR) ACR20 and ACR50 response rates at all time points (P < 0.01). ETN was well-tolerated, with no unexpected safety findings.

Conclusions ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic progression and improved clinical outcomes more effectively than MTX in this Japanese population.