Medicine, University of Texas Southwestern, Dallas, Texas, USA
Rheumatology, Stanford University, Palo Alto, California, USA.
Ann Rheum Dis. 2019 Nov;78(11):1454-1462. doi: 10.1136/annrheumdis-2019-215764. Epub 2019 Jul 30.
In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response.
Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised.
Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26.
Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.
在 SELECT-COMPARE 这项随机、双盲研究中，与安慰剂或阿达木单抗+甲氨蝶呤（MTX）相比，每日一次给予 15 毫克乌帕替尼可改善类风湿关节炎的体征和症状，且在 26 周时可抑制影像学进展，而安慰剂则无此作用。在此我们报告 48 周时继续使用原药物或因应答不足而转换为替代药物的患者的安全性和疗效。
接受 MTX 治疗的患者接受乌帕替尼 15 毫克、安慰剂或阿达木单抗治疗 48 周。如果患者在第 14/18/22 周时压痛关节数（TJC）或肿胀关节数（SJC）的改善＜20%，或临床疾病活动度指数（CDAI）＞10 分（第 26 周），则无需洗脱直接从安慰剂或阿达木单抗转换为乌帕替尼或乌帕替尼转换为阿达木单抗进行无洗脱抢救；第 26 周时，剩余的安慰剂患者转换为乌帕替尼。根据随机分组（未应答者推断）和抢救患者（实际观察）对疗效进行分析。每 100 患者-年报告治疗出现的不良事件。
与第 26 周时的应答情况一致，从第 26 周到 48 周，随机分组的应答情况，包括低疾病活动度、临床缓解以及疼痛和功能的改善，乌帕替尼组均优于阿达木单抗组；与安慰剂组相比，乌帕替尼组的影像学进展仍然较低（线性外推）。尽管两组转换患者均有应答，但与从乌帕替尼转换为阿达木单抗的患者相比，从阿达木单抗转换为乌帕替尼的患者在转换后 6 个月时达到 CDAI≤10 的比例更高。第 48 周时的安全性与第 26 周时相似。
与阿达木单抗+MTX 相比，乌帕替尼+MTX 表现出更优的临床和功能应答，且与安慰剂+MTX 相比，通过第 48 周时仍然抑制结构损伤。对阿达木单抗或乌帕替尼应答不足的患者在无需洗脱的情况下安全地转换为替代药物后，可实现有临床意义的应答。
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