Retrospective Cohort Study of Infliximab and Vederizumab in the Treatment of Moderate-to-severe Ulcerative Colitis
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摘要:
目的 比较英夫利西单抗（infliximab，IFX）及维得利珠单抗（vedolizumab，VDZ）在中重度溃疡性结肠炎（ulcerative colitis，UC）治疗中的疗效及安全性差异。 方法 回顾性收集自2020年01月至2023年12月于昆明医科大学第一附属医院确诊为中重度UC并使用IFX/VDZ治疗的患者129例，其中IFX治疗组65例，VDZ治疗组64例，剔除资料严重缺失及非疗效原因导致疗程不足14周患者19例，最终共纳入110例患者进行分析，其中IFX治疗组55例，VDZ治疗组55例。记录患者在治疗前（0周）及治疗14周、30周、54周的临床症状、疾病活动相关指标、内镜表现以及治疗过程中发生的不良反应，分析两种药物对于中重度UC治疗的疗效及安全性是否存在差异。 结果 2组患者在各项基线指标之间差异无统计学意义（P > 0.05）；IFX治疗组的炎症指标（WBC、PLT、ESR、CRP）水平在第14周高于VDZ治疗组，营养指标ALB水平在第30周低于VDZ治疗组，其差异具有统计学意义（P < 0.05）；其余实验室指标在各随访节点之间差异无统计学意义（P > 0.05）。IFX治疗组及VDZ治疗组的临床应答率在治疗第14周（81.8% vs 85.5%）、第30周（80.8% vs 92.5%）及第54周（91.3% vs 90.0%）差异无统计学意义（P > 0.05）；临床缓解率在治疗第14周（41.8% vs 49.1%）、第30周（50.0% vs 67.5%）及第54周（65.2% vs 63.3%）差异无统计学意义（P > 0.05）；内镜应答率在治疗第14周（54.3% vs 72.2%）、第30周（41.3% vs 73.3%）及第54周（60.0% vs 75.0%）差异无统计学意义（P > 0.05）；内镜缓解率在治疗第14周（34.3% vs 55.6%）及第54周（53.3% vs 54.2%）差异无统计学意义（P > 0.05），IFX治疗组的内镜缓解率在治疗第30周（23.5% vs 73.3%）低于VDZ治疗组，其差异具有统计学意义（P = 0.005）。IFX治疗组与VDZ治疗组的失应答率在治疗14周至30周期间 （7.3% vs 1.8%）差异无统计学意义（P > 0.05），IFX治疗组的失应答率在治疗第30周至54周期间（16.4% vs 0）高于VDZ治疗组，其差异具有统计学意义（P = 0.005）；IFX治疗组及VDZ治疗组不良反应发生率（10.9% vs 5.5%）之间差异无统计学意义（P > 0.05）。 结论 在中重度UC的治疗中，IFX治疗组与VDZ治疗组在第14周、54周的临床应答率及临床缓解率、内镜应答率、内镜缓解率之间未观察到显著差异，在第30周IFX治疗组的内镜缓解率低于VDZ治疗组；维持治疗过程中IFX治疗组的失应答率高于VDZ治疗组，提示IFX治疗组可能存在更高的远期耐药率；2种药物治疗过程中的不良反应发生率之间差异无统计学意义。 Abstract:Objective To compare the efficacy and safety of infliximab （IFX） and vedolizumab （VDZ） in the treatment of moderate-to-severe ulcerative colitis （UC）. Methods A total of 129 patients diagnosed with medium-to-severe ulcerative colitis and treated with IFX/VDZ in the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2023 were retrospectively collected, with 65 in the IFX treatment group and 64 in the VDZ treatment group. Afer excluding 19 patients whose treatment course was less than 14 weeks due to serious data missing or non-therapeutic reasons, a total of 110 patients were included for analysis, including 55 in the IFX treatment group and 55 in the VDZ treatment group. Clinical symptoms, indicators related to the disease activity, endoscopic manifestations and adverse reactions occurred during the treatment were recorded before the treatment （0 week） and 14, 30, and 54 weeks of treatment, and whether there were differences in the efficacy and safety of the two drugs in the treatment of moderate to severe UC was analyzed. Results There were no significant differences in the baseline indexes between the two groups （P > 0.05）. The levels of inflammatory indicators （WBC, PLT, ESR, CRP） in IFX treatment group were higher than those in VDZ treatment group at week 14, and the level of nutrition indicator ALB was lower than those in VDZ treatment group at week 30, with statistical significance （P < 0.05）. There was no significant difference in other laboratory indexes among follow-up nodes （P > 0.05）. The clinical response rate of IFX treatment group and VDZ treatment group was not significantly different at week 14 （81.8% vs 85.5%）, week 30 （80.8% vs 92.5%） and week 54 （91.3% vs 90.0%） （P > 0.05）. There was no significant difference in clinical response rate at week 14 （41.8% vs 49.1%）, week 30 （50.0% vs 67.5%） and week 54 （65.2% vs 63.3%） （P > 0.05）. There was no significant difference in endoscopic response rate at week 14 （54.3% vs 72.2%）, week 30 （41.3% vs 73.3%） and week 54 （60.0% vs 75.0%） （P > 0.05）. There was no significant difference in the endoscopic response rate at week 14 （34.3% vs 55.6%） and week 54 （53.3% vs 54.2%） （P > 0.05）. The endoscopic response rate at week 30 （23.5% vs 73.3%） in IFX treatment group was lower than that in VDZ treatment group, the difference was statistically significant （P = 0.005）. There was no significant difference between IFX group and VDZ group （7.3% vs 1.8%） during 14 to 30 weeks of the treatment （P > 0.05）, and IFX group had the higher non-response rate during 30 to 54 weeks of treatment （16.4% vs 0） than VDZ group. The difference was statistically significant （P = 0.005）. There was no significant difference in the incidence of adverse reactions between IFX treatment group and VDZ treatment group （10.9% vs 5.5%） （P > 0.05）. Conclusion During the treatment of moderate to severe UC, no significant difference has been observed in the clinical response rate, clinical remission rate, endoscopic response rate and endoscopic remission rate between the IFX treatment group and the VDZ treatment group at week 14 and week 54, and the endoscopic remission rate in the IFX treatment group is lower than that in the VDZ treatment group at week 30. The non-response rate of IFX treatment group is higher than that of VDZ treatment group during the maintenance treatment, suggesting that IFX treatment group may have a higher long-term drug resistance rate. There is no significant difference in the incidence of adverse reactions between the two drugs. -
Key words:
- Ulcerative colitis /
- Retrospective cohort study /
- Biological agent /
- Infliximab /
- Vedelizumab
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图 1 2治疗组不同随访点临床及内镜疗效比较
A：临床应答；B：内镜应答；C：临床缓解；D：内镜缓解；**P < 0.01。
Figure 1. Comparison of clinical and endoscopic effects at different follow-up points between the two treatment groups
图 2 2治疗组失应答率比较
**P < 0.01。
Figure 2. Comparison of non-response rate between the two treatment groups
图 3 2治疗组不良反应发生率对比
Figure 3. Comparison of the incidence of adverse reactions between the two treatment groups
表 1 2治疗组患者基线特征比较[n（%）/（$ \bar x \pm s $）/M（P25，P75）]（1）
Table 1. Comparison of baseline characteristics of patients between the two treatment groups[n（%）/（$ \bar x \pm s $）/M（P25，P75）]（2）
特征 IFX（n=55） VDZ（n=55） t/Z/χ2 P 性别 男 31（56.4） 28（50.9） 0.329 0.566 女 24（43.6） 27（49.1） 民族 汉族 49（89.1） 51（92.7） 0.440 0.507 少数民族 6（10.9） 4（7.3） 年龄/岁 46.0 ± 15.1 48.2 ± 16.9 0.732 0.466 发病年龄/岁 40（28，50） 39（27，53） 0.260 0.795 病程（a） 5（3，7） 6（3，11） 1.413 0.158 病变范围 直肠型（E1） 0 2（3.6） - 0.177 左半结肠型（E2） 4（7.3） 8（14.5） 全结肠型（E3） 51（92.7） 45（81.8） 疾病活动度 中度活动 23（41.8） 18（32.7） 0.972 0.324 重度活动 32（58.2） 37（67.3） Mayo（0周）/分 11（10.0，12.0） 11（9.0，11.0） −1.812 0.07 营养指标 BMI（0周）/（kg/m2） 20.08（18.0，22.0） 20.70（18.3，22.8） 0.577 0.564 
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表 1 2治疗组患者基线特征比较[n（%）/（$ \bar x \pm s $）/M（P25，P75）]（2）
Table 1. Comparison of baseline characteristics of patients between the two treatment groups[n（%）/（$\bar x \pm s $）/M（P25，P75）]（2）
特征 IFX（n=55） VDZ（n=55） t/Z/χ2 P HB（0周）/（g/L） 118.6 ± 25.5 112.4 ± 34.4 1.065 0.289 ALB（0周）/（g/L） 34.4 ± 6.3 35.7 ± 7.5 −1.029 0.306 炎症指标 WBC（0周）/（109/L） 7.8 ± 2.6 7.64 ± 2.2 0.249 0.804 PLT（0周）/（109/L） 358.5 ± 106.7 351.2 ± 112.5 0.348 0.729 ESR（0周）/（mm/h） 30（19.0，46.0） 30（14.0，53.0） −0.185 0.853 CRP（0周）/（mg/L） 18.60（6.4，58.1） 12.40（3.1，45.7） −1.166 0.244
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表 2 2治疗组各随访点营养指标比较[ M（P25，P75） /（$ \bar x \pm s $）]
Table 2. Comparison of nutritional indicators at each follow-up point between the two treatment groups[ M（P25，P75） /（$ \bar x \pm s $）]
营养指标 时间 IFX VDZ t/Z P BMI/（kg/m2） 14周 20.20（18.55，22.04） 21.30（19.33，23.44） 1.267 0.205 30周 20.26（19.11，22.33） 21.96（19.03，23.58） 0.828 0.408 54周 20.96（19.10，26.35） 21.00（18.59，22.78） 0.503 0.615 HB/（g/L） 14周 132（100，146） 136（111，149） 1.273 0.203 30周 131（122，151） 133（117，146） 0.425 0.671 54周 139.78 ± 24.04 131.77 ± 26.54 1.134 0.262 ALB/（g/L） 14周 38.38 ± 5.17 40.06 ± 5.10 1.666 0.099 30周 39.64 ± 4.95 42.37 ± 4.82 2.399 0.019* 54周 41.25（37.73，45.55） 44.10（39.60，46.10） 1.332 0.183 *P < 0.05。
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表 3 2治疗组各随访点炎症指标比较[（$ \bar x \pm s $）/ M（P25，P75）]
Table 3. Comparison of inflammatory indicators at each follow-up point between the two treatment groups[（$ \bar x \pm s $）/ M（P25，P75）]
炎症指标 时间 IFX VDZ t/Z P WBC（109/L） 14周 6.06 ± 1.96 7.00 ± 2.09 2.400 0.018* 30周 6.28 ± 2.04 6.31 ± 1.63 0.088 0.930 54周 6.06 ± 2.06 6.20 ± 1.1.43 0.281 0.779 PLT（109/L） 14周 290（257，379） 251（216，320） 2.021 0.043* 30周 290（238，388） 268（227，312） 1.409 0.159 54周 270（220，342） 265（228，338） 0.099 0.921 ESR（mm/h） 14周 30（10，42） 10（5，21） 3.106 0.002* 30周 22（9，31） 9（5，20） 1.537 0.124 54周 13.21 ± 10.50 13.50 ± 11.65 0.076 0.940 CRP（mg/L） 14周 4.00（1.03，12.87） 1.40（0.68，3.29） 2.882 0.004* 30周 3.58（1.10，12.73） 3.20（0.60，7.94） 1.435 0.151 54周 1.77（0.72，8.80） 1.42（0.59，7.04） 0.557 0.578 *P < 0.05。
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