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。     

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.     

类风湿关节炎患者疲乏症状与疾病活动及生活质量关系的研究

目的 评价类风湿关节炎(RA)患者疲乏症状的发生率,并探讨疲乏与疾病活动、功能状态及生活质量的关系.方法 入选RA患者230例,应用疲乏目视模拟测试表(VAS)评分评估患者疲乏的发生率,探讨疲乏评分≥50 mm和<50 mm的RA患者临床指标、疾病活动、功能状态、生活质量及实验室炎性指标的变化,并对疲乏的相关因素进行分析.结果 85.7%的RA患者疲乏VAS评分≥20 mm,51.7%的患者疲乏VAS评分≥50 mm.疲乏评分≥50 mm的患者与<50 mm的患者相比,晨僵时间、疼痛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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)得分及红细胞沉降率(ESR)明显增高,而健康测量量表SF-36中有关生理和心理健康8个维度得分明显降低,差异均有统计学意义.双变量相关分析显示:疲乏与晨僵时间、疼痛VAS评分、PGA、医生总体评价、TJC、TJI、SJC、SJI、DAS28、HAQ及SF-36中有关生理和心理健康的8个维度均有低至中等程度的相关性,与ESR、C反应蛋白(CRP)之间具有较弱的相关性.结论 疲乏是RA患者的一个重要症状,并与患者疼痛、疾病活动、功能状态及生活质量相关.     

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.     

依那西普治疗中国接受甲氨蝶呤治疗的活动性类风湿关节炎患者随机双盲多中心对照研究

目的 研究依那西普每周1次皮下注射50 mg对接受甲氨蝶呤(MTX)治疗的中国活动性类风湿关节炎(RA)患者的疗效及安全性.方法 本研究由2部分组成:12周双盲治疗阶段和12周安全性开放研究阶段.双盲期间的随机通过临床操作随机化(CORE)系统完成.在双盲阶段,RA患者被随机分配到依那西普50mg治疗组或安慰剂组,每周1次皮下注射给药,同时坚持一定剂量MTX给药.完成双盲治疗的RA患者在开放治疗中均接受每周1次依那西普50 mg和MTX给药.以美国风湿病学会(ACR)疗效评价指标ACR 20为主要终点疗效指标.次要终点疗效指标包括医生和患者总体评价、晨僵持续时间、疼痛目视模拟测试表(VAS)、健康评估问卷(HAQ)、C反应蛋白(CRP)值、疼痛和肿胀关节数.并且比较2组的安全性结果.采用Fisher精确概率法对主要终点疗效指标第12周ACR 20应答情况及其他次要终点疗效指标进行分析.使用协方差方法分析连续终点相对于基线的变化.结果 双盲治疗期间修正的意向性治疗人群(Mitt)共有156例患者,其中依那西普+MTX组77例.安慰剂+MTX组79例,149例患者完成双盲阶段的治疗.治疗4周时,依那西普+MTX组ACR 20有效率为39%(30/77),安慰剂+MTX组为16%(13/79),差异有统计学意义(P<0.01);12周时,依那西普+MTX组ACR 20有效率为62%(48/77),安慰剂+MTX组为23%(18/79),差异有统计学意义(P<0.01).其他疗效指标包括医生和患者总体评价、晨僵持续时间、疼痛VAS、HAQ、CRP、触痛关节数、肿胀关节数等均从第4周开始,在依那西普+MTX组明显优于安慰剂+MTX组(P<0.01).总的不良反应发生率在2组间差异无统计学意义.结论 与安慰剂治疗活动性RA相比.依那西普治疗活动性RA起效迅速、疗效显著.依那西普50 mg+MTX每周1次给药治疗中国成年活动性RA患者24周,耐受性良好.     

活动性类风湿关节炎患者生活质量及影响因素分析

目的 探讨活动性类风湿关节炎(RA)患者的健康相关生活质量及其影响因素.方法 采用健康测量量表SF-36对127例活动件RA患者的生活质量进行评价,与非活动性RA患者及健康对照者进行比较,并探讨晨僵时间、疼痛目视模拟测试表(VAS)评分、疲乏VAS评分、患者对自身健康状况的总体评价(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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)等临床评价指标与生活质量的相关性.结果 活动性RA患者SF-36量表各维度评分均明显低于健康对照者(P<0.01);与非活动性RA患者相比,除总体健康(GH)外,活动性RA患者其他各维度评分均明显低于非活动性RA患者(P<0.01).疲乏VAS评分、PGA、医生总体评价、HAQ、DAS28是与SF-36量表各维度相关最为密切的临床参数,这些临床参数与各个维度的评分均相关(r=-0.189～-0.673).疼痛VAS评分与除情感职能(RE)外的各维度评分呈低～中度相关(r=-0.201～-0.547);TJI与除GH、RE外的各维度相关(r=-0.189～-0.466),TJC与除GH、社会功能(SF)、RE外的各维度相关(r=-0.179～-0.416),红细胞沉降率与3个维度相关(r=-0.180～-0.266).结论 活动性RA患者的生活质量明显下降,疾病活动、功能状态与患者的生活质量密切相关.     

活动性类风湿关节炎患者生活质量及影响因素分析

目的 探讨活动性类风湿关节炎(RA)患者的健康相关生活质量及其影响因素.方法 采用健康测量量表SF-36对127例活动件RA患者的生活质量进行评价,与非活动性RA患者及健康对照者进行比较,并探讨晨僵时间、疼痛目视模拟测试表(VAS)评分、疲乏VAS评分、患者对自身健康状况的总体评价(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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)等临床评价指标与生活质量的相关性.结果 活动性RA患者SF-36量表各维度评分均明显低于健康对照者(P<0.01);与非活动性RA患者相比,除总体健康(GH)外,活动性RA患者其他各维度评分均明显低于非活动性RA患者(P<0.01).疲乏VAS评分、PGA、医生总体评价、HAQ、DAS28是与SF-36量表各维度相关最为密切的临床参数,这些临床参数与各个维度的评分均相关(r=-0.189～-0.673).疼痛VAS评分与除情感职能(RE)外的各维度评分呈低～中度相关(r=-0.201～-0.547);TJI与除GH、RE外的各维度相关(r=-0.189～-0.466),TJC与除GH、社会功能(SF)、RE外的各维度相关(r=-0.179～-0.416),红细胞沉降率与3个维度相关(r=-0.180～-0.266).结论 活动性RA患者的生活质量明显下降,疾病活动、功能状态与患者的生活质量密切相关.     

活动性类风湿关节炎患者生活质量及影响因素分析

目的 探讨活动性类风湿关节炎(RA)患者的健康相关生活质量及其影响因素.方法 采用健康测量量表SF-36对127例活动件RA患者的生活质量进行评价,与非活动性RA患者及健康对照者进行比较,并探讨晨僵时间、疼痛目视模拟测试表(VAS)评分、疲乏VAS评分、患者对自身健康状况的总体评价(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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)等临床评价指标与生活质量的相关性.结果 活动性RA患者SF-36量表各维度评分均明显低于健康对照者(P<0.01);与非活动性RA患者相比,除总体健康(GH)外,活动性RA患者其他各维度评分均明显低于非活动性RA患者(P<0.01).疲乏VAS评分、PGA、医生总体评价、HAQ、DAS28是与SF-36量表各维度相关最为密切的临床参数,这些临床参数与各个维度的评分均相关(r=-0.189～-0.673).疼痛VAS评分与除情感职能(RE)外的各维度评分呈低～中度相关(r=-0.201～-0.547);TJI与除GH、RE外的各维度相关(r=-0.189～-0.466),TJC与除GH、社会功能(SF)、RE外的各维度相关(r=-0.179～-0.416),红细胞沉降率与3个维度相关(r=-0.180～-0.266).结论 活动性RA患者的生活质量明显下降,疾病活动、功能状态与患者的生活质量密切相关.     

活动性类风湿关节炎患者生活质量及影响因素分析

目的 探讨活动性类风湿关节炎(RA)患者的健康相关生活质量及其影响因素.方法 采用健康测量量表SF-36对127例活动件RA患者的生活质量进行评价,与非活动性RA患者及健康对照者进行比较,并探讨晨僵时间、疼痛目视模拟测试表(VAS)评分、疲乏VAS评分、患者对自身健康状况的总体评价(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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)等临床评价指标与生活质量的相关性.结果 活动性RA患者SF-36量表各维度评分均明显低于健康对照者(P<0.01);与非活动性RA患者相比,除总体健康(GH)外,活动性RA患者其他各维度评分均明显低于非活动性RA患者(P<0.01).疲乏VAS评分、PGA、医生总体评价、HAQ、DAS28是与SF-36量表各维度相关最为密切的临床参数,这些临床参数与各个维度的评分均相关(r=-0.189～-0.673).疼痛VAS评分与除情感职能(RE)外的各维度评分呈低～中度相关(r=-0.201～-0.547);TJI与除GH、RE外的各维度相关(r=-0.189～-0.466),TJC与除GH、社会功能(SF)、RE外的各维度相关(r=-0.179～-0.416),红细胞沉降率与3个维度相关(r=-0.180～-0.266).结论 活动性RA患者的生活质量明显下降,疾病活动、功能状态与患者的生活质量密切相关.     

活动性类风湿关节炎患者生活质量及影响因素分析

目的 探讨活动性类风湿关节炎(RA)患者的健康相关生活质量及其影响因素.方法 采用健康测量量表SF-36对127例活动件RA患者的生活质量进行评价,与非活动性RA患者及健康对照者进行比较,并探讨晨僵时间、疼痛目视模拟测试表(VAS)评分、疲乏VAS评分、患者对自身健康状况的总体评价(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)、疾病活动指数28(DAS28)、健康评估问卷(HAQ)等临床评价指标与生活质量的相关性.结果 活动性RA患者SF-36量表各维度评分均明显低于健康对照者(P<0.01);与非活动性RA患者相比,除总体健康(GH)外,活动性RA患者其他各维度评分均明显低于非活动性RA患者(P<0.01).疲乏VAS评分、PGA、医生总体评价、HAQ、DAS28是与SF-36量表各维度相关最为密切的临床参数,这些临床参数与各个维度的评分均相关(r=-0.189～-0.673).疼痛VAS评分与除情感职能(RE)外的各维度评分呈低～中度相关(r=-0.201～-0.547);TJI与除GH、RE外的各维度相关(r=-0.189～-0.466),TJC与除GH、社会功能(SF)、RE外的各维度相关(r=-0.179～-0.416),红细胞沉降率与3个维度相关(r=-0.180～-0.266).结论 活动性RA患者的生活质量明显下降,疾病活动、功能状态与患者的生活质量密切相关.     

Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study

OBJECTIVE: To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment. METHODS: Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial. RESULTS: At week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and C-reactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001). CONCLUSION: Even in patients without clinical improvement, treatment with infliximab plus MTX provided significant benefit with regard to the destructive process, suggesting that in such patients these 2 measures of disease are dissociated.     

Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study

OBJECTIVE: To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). METHODS: Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo. RESULTS: The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P=0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P<0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group. CONCLUSION: Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX.     

A randomized,double‐blind,placebo‐controlled,phase III study of the human anti‐tumor necrosis factor antibody adalimumab administered as subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate

Objective: Adalimumab is a fully human, monoclonal, antitumour necrosis factor antibody approved for the treatment of rheumatoid arthritis (RA) in more than 60 countries. We investigated the efficacy and safety of 40 mg every‐other‐week (eow) subcutaneous injections of adalimumab with methotrexate (MTX) versus placebo with MTX in Korean patients with RA with insufficient responses to MTX. Methods: This was a 24‐week, randomized, double‐blind, placebo‐controlled, phase III study conducted at six sites in Korea. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Secondary endpoints included ACR50, ACR70, and individual ACR components. Beginning at week 18, non‐responders (< 20% reduction in swollen and tender joint counts) could switch to rescue therapy with open‐label adalimumab 40 mg eow. Results: Of the 128 patients enrolled, 65 received adalimumab and 63 received placebo. An ACR20 response at week 24 was achieved by 61.5% of patients receiving adalimumab versus 36.5% receiving placebo (P < 0.01). ACR50 and ACR70 responses were achieved by 43.1% and 21.5% of adalimumab patients versus 14.3% and 7.9% of placebo patients (P < 0.001 and P < 0.05, respectively). Adalimumab significantly improved all seven ACR core components. Statistically significant improvements in ACR20 were observed with adalimumab as early as week 2. Adalimumab was generally well tolerated; there were no significant differences in incidences of adverse events between groups. Conclusions: In Korean patients with RA with insufficient responses to MTX, combination therapy with adalimumab and MTX was more efficacious than placebo and MTX in reducing RA signs and symptoms.     

Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial

OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.     

Golimumab,a new human anti–tumor necrosis factor α antibody,administered intravenously in patients with active rheumatoid arthritis: Forty‐eight–week efficacy and safety results of a phase III randomized,double‐blind,placebo‐controlled study

Objective

To assess the efficacy and safety of intravenous administration of golimumab in patients with rheumatoid arthritis (RA).

Methods

Adult patients with RA in whom disease activity was persistent despite treatment with methotrexate (MTX) at a dosage of 15–25 mg/week for ≥4 weeks were randomized to receive intravenous infusions of placebo plus MTX or intravenous infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX, every 12 weeks through week 48. Patients with <20% improvement in the swollen and tender joint counts could enter early escape and receive additional active treatment (week 16) or could have their dose regimen adjusted (week 24). The primary end point was the proportion of patients achieving a 50% response according to the American College of Rheumatology improvement criteria (ACR50) at week 14.

Results

The primary study end point was not met (at week 14, an ACR50 response was observed in 21% of the patients treated with golimumab plus MTX compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By week 24, significantly more patients treated with golimumab plus MTX had achieved an ACR50 response. Differences in the proportion of patients achieving an ACR50 response between the group receiving golimumab monotherapy and the group receiving placebo plus MTX were not significant at either week 14 (16% versus 13%) or week 24 (10% versus 9%). At week 48, the proportions of patients achieving ACR20 and ACR50 responses were highest among those who had received golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment with MTX was associated with a lower incidence of antibodies to golimumab. The most commonly reported adverse events through week 48 were infections (48% of patients treated with golimumab with or without MTX and 41% of patients receiving placebo plus MTX).

Conclusion

The primary end point was not met. However, intravenously administered golimumab plus MTX appears to have benefit in the longer‐term reduction of RA signs/symptoms in MTX‐resistant patients, with no unexpected safety concerns.

     

Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate

OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). RESULTS: The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. CONCLUSION: Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.     

Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for > or = 3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. RESULTS: A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. CONCLUSION: In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.     

Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone

OBJECTIVE: To compare the effects of methotrexate (MTX), alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic resonance imaging (MRI)-detected synovitis, bone edema, and erosive changes in patients with early rheumatoid arthritis (RA). METHODS: Forty-four patients with early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2, 6, 14, 22, 30, 38, and 46. Gadolinium-enhanced MRI scans of the metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed at baseline, week 18, and week 52. RESULTS: Scores for MRI-detected synovitis and bone edema improved over time in the 3 groups, with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups. Scores for MRI-detected erosion significantly increased over time in all groups. There were no differences in erosion scores between the MTX group and the other groups. It is of note that patients treated with IV MP showed more significant progression in MRI-detected erosions compared with patients treated with infliximab. At week 22, response rates according to the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group. At week 52, remission was achieved in 40% of patients in the MTX group and in 70% of patients in the IV MP and infliximab groups. Health Assessment Questionnaire scores improved significantly over time in all groups, with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone. No severe side effects were observed, except 1 case of MTX-related pneumonitis. CONCLUSION: The combination of MTX and infliximab is superior to MTX alone for reducing MRI-detected signs of synovitis and bone edema in patients with early RA. Progression of MRI-detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab.