Abstract：
BACKGROUND: Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited.
METHODS: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator.
RESULTS: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators.
CONCLUSIONS: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.
METHODS: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator.
RESULTS: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators.
CONCLUSIONS: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.
摘要：
背景：关于溃疡性结肠炎（UC）在诱导和维持期间批准的治疗方法的相对有效性和安全性的证据，包括upadacitinib（UPA），维多珠单抗（VEDO），ustekinumab（UST），和托法替尼（TOFA），是有限的。
方法：使用来自3期试验的数据，UPA与VEDO的疗效和安全性的三个安慰剂（PBO）锚定匹配调整的间接比较，UST,和TOFA(U-成就和U-成就，GEMINI-1联合国,和OCTAVE诱导和维持试验)已经进行。分别对来自UPA试验的基线特征进行加权以匹配每个比较试验。诱导反应者被重新随机分配到口服UPA15或30毫克，VEDO300mg静脉注射每8周（Q8W），UST90毫克SCQ8W，或口服TOFA5毫克，或PBO在维护。第44周（UST）/46周（VEDO）/52周（UPA/TOFA）的疗效结局根据诱导反应的可能性进行调整，并包括临床反应，临床缓解，和内窥镜改进。安全性结果包括不良事件（AE），严重不良事件（SAE），以及导致停药的不良事件(UPA与VEDO）。获益-风险通过需要治疗的数字(NNT)/伤害来评估，计算为达到UPA疗效/安全性结果的患者比例与比较者的差异的倒数。
结果：UPA15mg与VEDO和TOFA相比，表现出临床反应或内镜改善的患者比例更高（p<0.05）。UPA30mg与VEDO相比，显示所有治疗效果结果的患者比例明显更高，UST,或具有NNTs3.2-8.7的TOFA。AE的比例没有显着差异，SAEs,在两种剂量的UPA和比较物之间观察到导致停药的AE。
结论：在活动性UC患者中，更大的临床疗效，UPA与VEDO在维持1年后观察到相似的安全性，UST,TOFA,为UPA提出有利的收益-风险状况。尽管匹配的基线特征，试验设计和终点的差异可能仍然存在.
方法：使用来自3期试验的数据，UPA与VEDO的疗效和安全性的三个安慰剂（PBO）锚定匹配调整的间接比较，UST,和TOFA(U-成就和U-成就，GEMINI-1联合国,和OCTAVE诱导和维持试验)已经进行。分别对来自UPA试验的基线特征进行加权以匹配每个比较试验。诱导反应者被重新随机分配到口服UPA15或30毫克，VEDO300mg静脉注射每8周（Q8W），UST90毫克SCQ8W，或口服TOFA5毫克，或PBO在维护。第44周（UST）/46周（VEDO）/52周（UPA/TOFA）的疗效结局根据诱导反应的可能性进行调整，并包括临床反应，临床缓解，和内窥镜改进。安全性结果包括不良事件（AE），严重不良事件（SAE），以及导致停药的不良事件(UPA与VEDO）。获益-风险通过需要治疗的数字(NNT)/伤害来评估，计算为达到UPA疗效/安全性结果的患者比例与比较者的差异的倒数。
结果：UPA15mg与VEDO和TOFA相比，表现出临床反应或内镜改善的患者比例更高（p<0.05）。UPA30mg与VEDO相比，显示所有治疗效果结果的患者比例明显更高，UST,或具有NNTs3.2-8.7的TOFA。AE的比例没有显着差异，SAEs,在两种剂量的UPA和比较物之间观察到导致停药的AE。
结论：在活动性UC患者中，更大的临床疗效，UPA与VEDO在维持1年后观察到相似的安全性，UST,TOFA,为UPA提出有利的收益-风险状况。尽管匹配的基线特征，试验设计和终点的差异可能仍然存在.
