To evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial. Patients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years. Of 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses. Upadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile. NCT02706873.

中文翻译：

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UPADACITINIB 单药治疗与甲氨蝶呤单药治疗类风湿关节炎患者：SELECT-EARLY 随机对照试验中 5 年的疗效和安全性


在 3 期 SELECT-EARLY 试验的长期扩展 （LTE） 中，评估 upadacitinib 单药治疗与甲氨蝶呤 （MTX） 单药治疗在 5 年内中度至重度活动性类风湿性关节炎 （RA） 初治患者的疗效和安全性。患者随机接受 upadacitinib 15 mg 或 30 mg 或 MTX。未达到 CDAI 缓解且第 26 周时 < 压痛和肿胀关节计数改善 20% 的患者接受挽救治疗 （upadacitinib 组加用 MTX，MTX 组加用 upadacitinib）。对接受 upadatinib 15/30 mg 或 MTX 连续单药治疗的患者以及应用无反应者插补 （NRI） 的随机组进行疗效评估报告为观察 （AO）。在 5 年内总结了每 100 患者年的治疗中出现的不良事件 （TEAE）。在随机接受治疗的 945 名患者中，775 名 （82%） 完成了第 48 周并进入了 LTE 研究药物。与 MTX 相比，使用 upadacitinib 在 5 年内持续达到疾病活动目标的患者比例更高。在 AO 分析中，第 260 周时，53%/59% 的患者使用 upadacitinib 15/30 mg 达到 CDAI 缓解，而 MTX 组为 43%。NRI 分析显示，在第 260 周时，相对于 MTX，upadacitinib 的 CDAI、DAS28 （CRP） 和 ACR 反应更好 （所有比较，名义 P < .001）。与 MTX 相比，Upadacitinib 治疗在第 260 周对结构关节进展的抑制也更大。在接受 upadacitinib 30 mg 的患者中，大多数 TEAE 、严重 AE 和导致停药的 AE 在数值上较高。 upadacitinib 的严重感染、带状疱疹、肌酸磷酸激酶升高、非黑色素瘤皮肤癌和中性粒细胞减少症的发生率在数值上高于 MTX。upadacitinib 在 5 年内观察到的安全性特征与早期试验结果和综合 3 期安全性分析一致。在整个 5 年试验中，Upadacitinib 在 RA 患者中显示出优于 MTX 的临床反应。与 MTX 相比，upadacitinib 观察到更高的几种 AE 发生率，尤其是在 30 mg 组中。当用作 MTX 初治患者的单药治疗时，批准的 upadacitinib 15 mg 剂量显示出优于 MTX 的长期疗效和总体良好的收益-风险状况。NCT02706873。