背景:类风湿性关节炎(RA)治疗的一个目标是实现早期持续缓解;从长远来看,持续缓解的患者关节结构损伤和身体残疾较少。我们评估了阿巴西特+甲氨蝶呤与阿巴西特安慰剂+甲氨蝶呤的简化疾病活动指数(SDAI)缓解率,以及降低梯度(DE)对早期RA患者的影响。
方法:IIIb阶段,随机化,AVERT-2两阶段研究(NCT02504268)评估了每周阿巴蒂普+甲氨蝶呤与阿巴蒂普安慰剂+甲氨蝶呤。
方法:第24周SDAI缓解(≤3.3)。预先计划的探索性终点:持续缓解(40周和52周)患者的缓解维持,从第56周开始,持续48周(DE期),(1)继续联合阿巴坦服+甲氨蝶呤,(2)逐渐减量abatacept至每隔一周(EOW)+甲氨蝶呤24周,随后abatacept停药(abatacept安慰剂+甲氨蝶呤),或(3)停药甲氨蝶呤(阿比特西普单一疗法)。
结果:未达到主要研究终点:组合中21.3%(48/225)的患者和abatacept安慰剂+甲氨蝶呤组的16.0%(24/150)的患者在第24周达到SDAI缓解(p=0.2359)。在临床评估中有利于联合治疗的数字差异,患者报告的结局(PRO)和第52周放射学非进展。56周后,将147例接受阿巴蒂普+甲氨蝶呤持续缓解的患者随机分组(组合,n=50;DE/撤回,n=50;阿巴蒂普单药治疗,n=47),并输入DE。在DE第48周时,持续的联合治疗主要维持了SDAI缓解(74%)和PRO改善;阿巴蒂普安慰剂甲氨蝶呤(48.0%)和阿巴蒂普单药治疗(57.4%)观察到较低的缓解率。退伍前,降至abataceptEOW+甲氨蝶呤保留缓解。
结论:未达到严格的主要终点。然而,在获得持续SDAI缓解的患者中,与abatacept单药治疗或停药相比,持续的abatacept+甲氨蝶呤在数字上更能维持缓解。
背景:ClinicalTrials.gov标识符,NCT02504268。视频摘要(MP462241KB)。
类风湿性关节炎(RA)患者经历关节发炎和受损。RA是一种自身免疫性疾病,其中称为自身抗体的蛋白质,特别是抗瓜氨酸蛋白自身抗体,错误地瞄准患者自己的关节组织和器官,导致症状性炎症。成功的治疗可以将疾病的活动降低到称为缓解的状态。缓解的患者可能很少或没有症状,并且一些患者可能会减少他们的治疗。这里,我们报告了一个大的结果,国际研究着眼于两种治疗方法,abatacept和甲氨蝶呤,在RA和抗瓜氨酸蛋白自身抗体患者中。这项研究有两个部分。首先,看看有多少患者成功(缓解)每周阿巴蒂普和/或甲氨蝶呤治疗,其次,观察在继续治疗或减少治疗并停止时是否维持缓解。研究表明,治疗开始后6个月缓解的患者人数在接受abatacept和甲氨蝶呤治疗的患者与仅接受甲氨蝶呤治疗的患者之间没有很大差异。1年后服用阿巴泰普和甲氨蝶呤的患者缓解率较高。与刚接受abatacept治疗或减少并停止接受abatacept治疗的患者相比,当他们继续接受abatacept和甲氨蝶呤时,更多的患者也保持缓解。当abatacept减少时,更多的患者保持在缓解状态,而不是停止时。这项研究的结果可能有助于确定某些RA患者未来可能的治疗减少和/或停药计划。
BACKGROUND: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA.
METHODS: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate.
METHODS: SDAI remission (≤ 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy).
RESULTS: Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission.
CONCLUSIONS: The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal.
BACKGROUND: ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB).
Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease in which proteins called autoantibodies, particularly anti-citrullinated protein autoantibodies, target the patient’s own joint tissue and organs by mistake, leading to symptomatic inflammation. Successful treatment can decrease the disease’s activity to a state known as remission. Patients in remission may experience little or no symptoms and it may be possible for some to then be able to decrease their treatment. Here, we report the results of a large, international study that looked at two treatments, abatacept and methotrexate, in patients with RA and anti-citrullinated protein autoantibodies. The study had two parts. Firstly, to see how many patients had success (remission) with weekly abatacept and/or methotrexate treatment, and secondly, to see if remission was maintained when treatment was either continued or decreased and stopped. The study showed that the number of patients in remission 6 months after treatment started was not greatly different between patients treated with both abatacept and methotrexate and those treated with just methotrexate. Those taking abatacept and methotrexate together had better remission rates 1 year later. More patients also stayed in remission when they continued to receive both abatacept and methotrexate compared with those who were just treated with abatacept or when their abatacept treatment was decreased and stopped. More patients stayed in remission when abatacept was decreased than when it was stopped. The results from this study may help determine possible future treatment reduction and/or withdrawal plans for some patients with RA.