英夫利西单抗与改变病情的抗风湿药物治疗强直性脊柱炎的临床对比研究

目的 对单克隆抗体英夫利西单抗与传统改变病情的抗风湿药物(DMARDs)治疗强直性脊柱炎(AS)的临床疗效进行对比观察,以评价2种药物治疗AS的有效性和安全性.方法 60例确诊的活动期AS患者,随机分为治疗组及对照组,每组30例,治疗组分别于0、2、6、12周给予英夫利西单抗(5mg/kg),对照组给予传统DMARDs(柳氮磺吡啶或来氟米特),随访12周.观察主要疗效指标:治疗终点时达到AS疗效评价标准(ASAS)20的患者比例;次要疗效指标:治疗终点时达到ASAS 50的患者比例,不同时间点与基线值相比Bath AS疾病活动指数(BASDAI)、Bath AS功能指数(BASFI)、脊柱痛、脊柱炎症、患者总体评估指数(PGA)、目视模拟测试表(VAS)及红细胞沉降率(ESR)、C反应蛋白(CRP)变化的情况.计量资料采用t检验,计数资料采用x2检验.结果 2组患者在治疗第12周时与治疗前比较,ASAS 20(93%和47%)、ASAS 50(57%和27%)及BASDAI(2.8±0.4和4.9±1.2)、BASFI(2.8±0.9和4.0±1.1)、脊柱痛(2.5±1.0和3.9±1.2)、脊柱炎症(2.3±1.1和4.4±1.2)、PGA VAS(2.6±1.5和4.8±1.1)及ESR[(9±5)和(26±12)mm/1 h]、CRP[(5±3)和(19±12)mg/L]均改善,差异具有统计学意义(P<0.05).其中英夫利西单抗治疗组改善更为明显,优于传统DMARDs组(P<0.05).2组患者均无严重不良反应发生,最常见的不良反应为上呼吸道感染、胃肠道刺激症状及输液反应,英夫利西单抗组不良反应的发生率明显低于传统DMARDs组.结论 英夫利西单抗与传统DMARDs比较,能迅速减轻AS的症状与体征,并可改善AS患者的功能、活动范围和生活质量,具有良好的安全性和耐受性.     

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.     

依那西普治疗强直性脊柱炎的多中心、随机、双盲、安慰剂对照临床研究

目的 评价依那西普治疗活动性强直性脊柱炎(AS)的短期疗效与安全性.方法 为期12周(双盲治疗期和开放治疗期各6周)的随机、双盲、安慰剂对照的Ⅲ期临床研究.双盲期试验组和对照组患者分别接受依那西普或空白模拟制剂50 mg,1次/周,皮下注射;开放期2组均接受依那西普50 mg,1次/周,皮下注射.分别在第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20%改善程度(ASAS 20)的受试者比例,次要疗效指标为达到ASAS 40%改善程度(ASAS 40)、ASAS 50%改善程度(ASAS 50)、ASAS 70%改善程度(ASAS 70)和ASAS标准中6项改善5项(ASAS 5/6)的受试者比例、受试者总体评估、医生总体评估、夜间和总体背部疼痛、Bath强直性脊柱炎功能指数(BASFI)、Bath强直性脊柱炎疾病活动指数(BASDAI)、脊柱活动度、关节评价及生活质量.所有受试者均进行安全性评价.结果 152例患者入选本研究,对照组78例,试验组74例.双盲期第2周时,2组达到ASAS 20的受试者比例差异即有统计学意义.第6周时,试验组86.5%(64/74)的受试者达到ASAS 20,对照组为29.5%(23/78),差异有统计学意义(P＜0.001).次要疗效指标ASAS 40、ASAS 50、ASAS 70、ASAS 5/6、受试者总体评估、医生总体评估、夜间和总体背部疼痛、BASFI、BASDAI、脊柱活动度、关节评价及生活质量均有明显改善.不良反应大多为轻度,最常见的为肝酶水平升高、注射部位反应和鼻咽炎,未见死亡和严重不良事件.结论 依那西普治疗活动性AS,起效迅速,疗效显著,安全性好.     

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.     

负荷剂量英夫利昔单抗治疗强直性脊柱炎的临床疗效及疗效预测因素分析

目的 探讨负荷剂量的抗肿瘤坏死因子(TNF)-α单克隆抗体英夫利昔单抗治疗强直性脊柱炎(AS)的临床疗效和达到临床疗效的预测因素.方法 本研究以一项2个中心的开放性Ⅱ期临床试验为基础,纳入确诊的AS患者,并且处于疾病活动期,即Bath AS疾病活动指数(BASDAI)和脊柱痛评分均≥4.患者分别在试验的第0、2、6周静脉滴注英夫利昔单抗5 mg/kg,在10周时对其临床疗效进行评估,以10周时是否达到ASAS 20,ASAS 40和BASDAI 50为疗效标准,对人口学参数[性别、年龄、病程、人类白细胞抗原(HLA)-B27阳性与否]和基线时疾病活动指标[BASDAI、脊柱炎症、脊柱痛VAS、夜间痛VAS、患者总体评估指数、BASFI、BASMI、肌腱端指数、整体关节肿胀指数、扩胸度、红细胞沉降率(ESR)和C反应蛋白(CRP)和BASRI]17个指标进行Logistic单因素和多因素疗效预测分析.结果 63例患者(男性占79%,平均年龄32岁,平均病程10年,HLA-B27阳性占90%)纳入并完成研究,第10周试验结束时,84%的患者达到ASAS 20改善;.75%的患者达到ASAS 40改善;70%的患者达到BASDAI评分改善＞50%.Logistic单因素和多因素分析显示:人口学参数和基线时疾病活动指标均未显示能预测患者的疗效.结论 英夫利昔单抗治疗AS疗效明显,基线时的人口学参数、疾病活动性的临床和实验室指标不能预测疗效.     

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.     

抗肿瘤坏死因子α单克隆抗体治疗强直性脊柱炎的短期临床观察

目的评价负荷剂量的抗肿瘤坏死因子α单克隆抗体infliximab治疗强直性脊柱炎（AS）的临床疗效和安全性。方法本研究为2个中心的开放性Ⅱ期临床试验,患者为确诊的AS患者,并且疾病处于活动期。患者分别在试验的第0、2、6周接受静脉输注infliximab5mg／kg,并随访至10周,主要疗效指标为达到AS疗效评价标准20（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BathAS疾病活动指数（BASDAI）、BathAS功能指数、BathAS测量指数、脊柱痛、夜间痛、脊柱炎症、病人总体评估指数、肌腱端炎指数、整体关节肿胀指数、生活质量健康问卷SF-36改善的状况。结果63例患者（男性占79％,平均年龄32岁,平均病程10年,HLA-B27阳性占90％）纳入研究,第10周试验结束时,84％的患者达到ASAS20的改善程度;有30％的患者达到临床显效标准;70％的患者达到BASDAI评分改善大于50％,54％的患者达到BASDAI评分改善大于70％。其他各项疗效指标也反映出相似的改善程度及趋势。最常见的不良反应为上呼吸道感染和皮肤及其附属器官的损害,其次是肝功能异常,2例患者发生严重的皮炎伴有脱发,1例患者在第3次输注药物过程中因出现输注反应而停药。近期随访结果显示,疗效可持续2～8个月,停止治疗后无新的不良反应发生。结论负荷剂量infliximab的安全性和耐受性好,能迅速减轻AS的症状和体征,并可改善AS患者的功能、活动范围和生活质量。     

强直性脊柱炎患者疲乏症状的评定

目的 评价强直性脊柱炎(AS)患者疲劳症状的发生率,并探讨发生疲劳的相关因素.方法 应用Bath AS疾病活动指数(BASDAI)量表中的疲劳项目对AS患者的疲劳症状进行评分,评价AS患者疲劳的发生率,并探讨其与临床评价指标BASDAI、Bath AS功能指数(BASFI)、Bath AS测量指数(BASMI)、脊柱痛、夜间痛、脊柱炎症、肌腱端指数、整体关节肿胀指数、生活质量及实验室炎性指标红细胞沉降率(ESR)、C反应蛋白(CRP)的相关性.结果 共纳入73例AS患者,将患者根据疲劳症状评分分为≥5分组和＜5分组,其中68.5%的患者疲劳项目的 评分≥5分,≥5分组和＜5分组相比年龄、性别、病程等差异无统计学意义.双变量相关分析表明疲劳与疾病活动性、功能状况、脊柱痛、夜间痛及BASMI相关,与生理健康的4个维度及心理健康的1个维度相关,与ESR、CRP无相关性.结论 疲劳是AS患者的一个重要的症状,应用BASDAI量表中的疲劳项目评分可以较好地进行疲劳症状评定.     

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.     

强直性脊柱炎肌腱端炎与临床及实验室炎性指标的关系

目的 探讨强直性脊柱炎（AS）患者肌腱端炎与有关临床及实验室指标的相关性。方法 触压66个肌腱附着点，计算肌腱端指数，探讨AS患者肌腱端炎的严重程度与临床评价指标BathAS疾病活动指数（BASDAI）、Bath AS功能指数（BASFI）、Bath AS测量指数（BASMI）、脊柱痛、夜间痛、脊柱炎症、整体关节肿胀指数、生活质量及实验室炎性指标血沉（ESR）、C反应蛋白（CRP）的相关性。结果 共纳入78例AS患者，均处于疾病活动期，多数患者（98．7％）有肌腱端炎，肌腱端炎好发于骶髂关节、腰椎突起、颈椎突起、坐骨结节及跟腱附着点。双变量相关分析显示肌腱端炎与疾病活动性，脊柱痛、脊柱炎症、功能状况、夜间痛、AS测量指数及扩胸度相关，与ESR、CRP无关。结论 肌腱端指数可以反映AS患者疾病活动性，是评价疾病活动性的有效临床方法。     

Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open,observational, extension study of a three-month,randomized, placebo-controlled trial

OBJECTIVE: Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. METHODS: This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. CONCLUSION: Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.     

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.     

Six-month results of a double-blind,placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis

OBJECTIVE: There is increasing evidence that tumor necrosis factor alpha (TNFalpha) is centrally involved in the pathogenesis of ankylosing spondylitis (AS) and other spondylarthritides. This study was designed to investigate the efficacy of anti-TNFalpha therapy with etanercept, a 75-kd receptor fusion protein, in active AS. METHODS: This multicenter trial had 2 phases: an initial placebo-controlled period of 6 weeks' duration and an observational phase lasting 24 weeks. Thirty patients with active AS were included. They were randomized into 2 groups, which received either etanercept (25 mg twice weekly) (n = 14) or placebo (n = 16) for 6 weeks. Then both groups were treated with etanercept. Nonsteroidal antiinflammatory drug (NSAID) treatment could be continued, but disease-modifying antirheumatic drugs (DMARDs) and steroids had to be withdrawn prior to the study. All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index, Bath AS Metrology Index, pain level on a numeric rating scale, quality of life by the Short Form 36, and C-reactive protein (CRP) level were assessed. The primary outcome parameter was a >or=50% improvement in the BASDAI. RESULTS: Treatment with etanercept resulted in at least a 50% regression of disease activity in 57% of these patients at week 6, versus 6% of the placebo-treated patients (P = 0.004). After the placebo-treated patients switched to etanercept, 56% improved. The mean +/- SD BASDAI improved from 6.5 +/- 1.2 at baseline to 3.5 +/- 1.9 at week 6 in the etanercept group, with no improvement in the placebo group (P = 0.003 between groups). Similarly, pain, function, mobility, and quality of life improved with etanercept but not with placebo at week 6 (P < 0.05). Mean CRP levels decreased significantly with etanercept but not with placebo (P = 0.001). There was ongoing improvement in all parameters in both groups until week 12 and week 18, respectively (i.e., throughout the period of etanercept treatment). Disease relapses occurred a mean +/- SD of 6.2 +/- 3.0 weeks after cessation of etanercept. No severe adverse events, including major infections, were observed during the trial. CONCLUSION: This study shows that on a short-term basis (3 months), treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids. After cessation of therapy, almost all patients experienced a relapse within a few weeks. Thus, it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process.     

Long‐term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: An open,observational, extension study of a three‐month,randomized, placebo‐controlled trial

Objective

Treatment of ankylosing spondylitis (AS) with infliximab, an anti–tumor necrosis factor α monoclonal antibody, was shown to be efficacious in patients with active disease during a 3‐month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1‐year period.

Methods

This study was an open, observational, extension study of a 3‐month, randomized, placebo‐controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12‐week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Results

At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent‐to‐treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31–63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36–67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in ∼70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study.

Conclusion

Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.

     

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.     

Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study

OBJECTIVE: To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis (AS) using MRI and DXA to monitor its impact on bone. METHODS: In this single centre study 42 subjects with active AS were treated with methotrexate and were randomly assigned, in a ratio of 2:1, to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks. The primary outcome was improvement in disease activity as shown by the BASDAI at week 30. MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density. RESULTS: Both therapeutic agents were well tolerated with no dropouts due to adverse events. A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 (p = 0.017) than in the placebo arm, but this was not maintained by week 30 (p = 0.195), 8 weeks after the last infusion, at which stage disease flares were reported by some subjects. MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group (p = 0.016). CONCLUSIONS: Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI. However, disease flares were reported 8 weeks after the last infusion, indicating that addition of methotrexate failed to extend the infliximab dosing interval.     

Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis

OBJECTIVE: To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor alpha, for the treatment of patients with ankylosing spondylitis (AS). METHODS: Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). RESULTS: Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. CONCLUSIONS: Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.