PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: NCT02706873.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: NCT02706873.
摘要：
背景：评估upadacitinib单药治疗与甲氨蝶呤（MTX）单药治疗在3期SELECT-EARLY试验长期延伸（LTE）中至重度活动性类风湿关节炎（RA）患者中5年内的疗效和安全性。
方法：患者随机接受upadacitinib15mg或30mg或MTX。在第26周未达到CDAI缓解且关节压痛和肿胀计数改善<20％的患者接受了抢救治疗（在upadacitinib组中添加MTX，在MTX组中添加upadacitinib）。对5年的疗效评估进行了评估，并报告为接受upadacitinib15/30mg或MTX连续单一疗法的患者的观察（AO），并通过随机组应用无反应者填补（NRI）。每100名患者年的治疗引起的不良事件（TEAE）在5年内进行了总结。
结果：在945例患者中，775(82%)完成第48周并进入研究药物的LTE。与MTX相比，使用upadacitinib的患者在5年内始终达到疾病活动目标的比例更高。在AO分析中，在第260周时，53％/59％的患者使用upadacitinib15/30mg获得CDAI缓解，而43％的患者使用MTX。NRI分析显示CDAI更好，DAS28(CRP),和在第260周使用upadacitinib相对于MTX的ACR反应（所有比较，标称P<.001)。与MTX相比，Upadacitinib治疗还导致在第260周期间对结构性关节进展的抑制更大。大多数TEAE,严重的AE，在接受upadacitinib30mg的患者中，导致停药的AE在数字上较高。严重感染率,带状疱疹,肌酸磷酸激酶升高，非黑色素瘤皮肤癌，和中性粒细胞减少在数值上高于MTX。观察到的upadacitinib5年的安全性与早期试验结果和综合3期安全性分析一致。
结论：Upadacitinib在整个5年试验中在RA患者中表现出更好的临床反应。使用upadacitinib观察到几种AE的发生率更高，尤其是在30毫克组中，与MTX相比。当用作MTX初治患者的单一疗法时，与MTX相比,批准的upadacitinib15mg剂量显示出更好的长期疗效和总体有利的获益-风险状况.
背景：NCT02706873。
方法：患者随机接受upadacitinib15mg或30mg或MTX。在第26周未达到CDAI缓解且关节压痛和肿胀计数改善<20％的患者接受了抢救治疗（在upadacitinib组中添加MTX，在MTX组中添加upadacitinib）。对5年的疗效评估进行了评估，并报告为接受upadacitinib15/30mg或MTX连续单一疗法的患者的观察（AO），并通过随机组应用无反应者填补（NRI）。每100名患者年的治疗引起的不良事件（TEAE）在5年内进行了总结。
结果：在945例患者中，775(82%)完成第48周并进入研究药物的LTE。与MTX相比，使用upadacitinib的患者在5年内始终达到疾病活动目标的比例更高。在AO分析中，在第260周时，53％/59％的患者使用upadacitinib15/30mg获得CDAI缓解，而43％的患者使用MTX。NRI分析显示CDAI更好，DAS28(CRP),和在第260周使用upadacitinib相对于MTX的ACR反应（所有比较，标称P<.001)。与MTX相比，Upadacitinib治疗还导致在第260周期间对结构性关节进展的抑制更大。大多数TEAE,严重的AE，在接受upadacitinib30mg的患者中，导致停药的AE在数字上较高。严重感染率,带状疱疹,肌酸磷酸激酶升高，非黑色素瘤皮肤癌，和中性粒细胞减少在数值上高于MTX。观察到的upadacitinib5年的安全性与早期试验结果和综合3期安全性分析一致。
结论：Upadacitinib在整个5年试验中在RA患者中表现出更好的临床反应。使用upadacitinib观察到几种AE的发生率更高，尤其是在30毫克组中，与MTX相比。当用作MTX初治患者的单一疗法时，与MTX相比,批准的upadacitinib15mg剂量显示出更好的长期疗效和总体有利的获益-风险状况.
背景：NCT02706873。
