背景:类风湿性关节炎是一种慢性炎症性疾病,具有公认的女性优势。在对NORD-STAR试验的事后分析中,我们的目的是研究三种不同的生物治疗联合甲氨蝶呤与主动常规治疗24周内缓解率的性别差异,早期类风湿关节炎患者。
方法:NORD-STAR是一个多中心,调查员发起的,评估者盲化,第四阶段,随机,早期类风湿关节炎的对照试验,在丹麦完成,芬兰,冰岛,挪威,瑞典,和荷兰。新诊断的病人,对改善疾病的抗风湿药幼稚,年龄在18岁或以上的早期类风湿性关节炎和症状持续时间少于24个月被随机分配(1:1:1:1)接受积极的常规治疗,赛托珠单抗-聚乙二醇,abatacept,或者托珠单抗.研究医生或研究护士在病例报告表中报告了性别。没有收集性别数据。缓解结果用Logistic广义估计方程(GEE)分析,使用logit链接和可交换相关矩阵。该模型包括治疗,时间,性别,以及相关的互动。对于这个事后分析,共同的主要结局是性别之间临床疾病活动指数(CDAI)缓解(CDAI评分≤2·8)随时间和第24周时的差异,采用交互作用项(在每次治疗比较中男性和女性)评估,并使用积极的常规治疗作为参考.我们提出了调整后的平均边际差异缓解率(风险差异)与95%CIs。
结果:在2012年12月14日至2018年12月11日之间,招募了812例患者并随机分配;217例接受了积极的常规治疗,203接受赛托珠单抗-pegol,204收到abatacept,188人接受了托珠单抗治疗。所有812例患者均纳入本分析;561例(69%)为女性,251例(31%)为男性。在24周时观察到的CDAI缓解率在男性中在数字上高于女性,尽管基线时疾病活动度相当(55%vs积极常规治疗的50%,57%与52%使用赛托珠单抗-pegol,65%vs51%与abatacept,托珠单抗为61%vs40%)。在调整后的分析中,以积极的常规治疗为参考,男性和女性之间的唯一显着差异是托珠单抗组(pinteraction=0·015);托珠单抗组的男性CDAI缓解的可能性更高,随着时间的推移,积极的常规治疗组的男性(0·12;95%CI0·00至0·23),托珠单抗组女性的缓解概率低于主动常规治疗组女性(-0·05,95%CI-0·13~0·02).
结论:在第24周,所有四个治疗组中,男性的缓解率明显高于女性,这表明这种普遍的性别差异与治疗无关。tocilizumab的男性和女性之间的差异明显更大,白细胞介素(IL)-6抑制剂,比积极的常规治疗,提示IL-6阻断可能的额外的基于性别的效应。
背景:无。
BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease with a well-recognised female preponderance. In this post-hoc analysis of the NORD-STAR
trial, we aimed to examine sex differences in remission rates with three different biological treatments combined with methotrexate versus active conventional treatment over 24 weeks, in patients with early rheumatoid arthritis.
METHODS: NORD-STAR was a multicentre, investigator-initiated, assessor-blinded, phase 4, randomised, controlled
trial of early rheumatoid arthritis, done in Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients, naive to disease-modifying antirheumatic drugs, aged 18 years or older with early rheumatoid arthritis and with a symptom duration less than 24 months were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab-pegol, abatacept, or tocilizumab. Sex was reported in case report forms by
study physicians or by
study nurses. Data on gender were not collected. Remission outcomes were analysed with logistic generalised estimating equations (GEE), using a logit link and exchangeable correlation matrix. The model included treatment, time, sex, and the relevant interactions. For this post-hoc analysis, the co-primary outcomes were differences in Clinical Disease Activity Index (CDAI) remission (CDAI score ≤2·8) between sexes over time and at week 24, assessed with interaction terms (men vs women within each treatment comparison) and using active conventional treatment as the reference. We present adjusted average marginal differences in remission rates (risk differences) with 95% CIs.
RESULTS: Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; 217 received active conventional treatment, 203 received certolizumab-pegol, 204 received abatacept, and 188 received tocilizumab. All 812 patients were included in this analysis; 561 (69%) were women and 251 (31%) were men. Observed CDAI remission rates at 24 weeks were numerically higher among men than among women despite comparable disease activity at baseline (55% vs 50% with active conventional treatment, 57% vs 52% with certolizumab-pegol, 65% vs 51% with abatacept, and 61% vs 40% with tocilizumab). In the adjusted analysis, with active conventional treatment as the reference, the only significant difference between men and women was in the tocilizumab group (pinteraction=0·015); men in the tocilizumab group had a higher probability of CDAI remission, on average over time, than did men in the active conventional treatment group (0·12; 95% CI 0·00 to 0·23), whereas women in the tocilizumab group had a lower probability of remission than did women in the active conventional treatment group (-0·05, 95% CI -0·13 to 0·02).
CONCLUSIONS: Numerically higher remission rates were observed in men than in women in all four treatment groups at week 24, suggesting that this generalised sex difference is not related to the treatment. The difference between men and women was significantly greater with tocilizumab, an interleukin (IL)-6 inhibitor, than with active conventional treatment, suggesting a possible additional sex-based effect specific for IL-6 blockade.
BACKGROUND: None.