Background

Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from a national population-based registry with no hierarchical prescribing order. We hypothesised immunotherapy co-therapy would increase persistence for anti-TNF agents, but not for non-anti-TNF agents due to reduced immunogenicity.

Methods

A randomly selected ten per cent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005 and June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Factors affecting discontinuation were evaluated using multivariate proportional hazard regression.

Results

886 patients consisting of 1294 lines of therapy (992 CD, 302 UC, 2778 person-years of follow-up) were included. In CD, UST had the highest overall persistence rate (median persistence rate was > 74.6% where 24.6 months is the maximum follow-up time recorded), followed by VDZ, IFX and ADA (p = 0.03) (Figure 1). UST had the highest persistence as first, second and third-line therapies (p < 0.05). In UC, VDZ had the highest persistence rate (median persistence rate was >50.3% where 47.4 months is the maximum follow-up time recorded), followed by IFX and ADA (p < 0.001) (Figure 2). VDZ had the highest persistence rates as first-line therapy (p < 0.001), while second and third-line therapies did not demonstrate significant differences.Persistence of biological agents correlated with immunomodulator co-therapy in CD (R²: 0.65 p < 0.001) and UC (R²: 0.50 p < 0.001). Thiopurine co-therapy significantly increased persistence for IFX and ADA in CD and UC (p < 0.001) (Figures 3 and 4) but was not significant for UST and VDZ. Methotrexate decreased persistence for VDZ in UC and had no effects on UST, IFX and ADA in UC and CD. In acute-severe UC, there were no significant differences between IFX as monotherapy vs. co-therapy.On multivariate analysis, higher persistence was seen in males (HR: 0.75 95% CI: 0.59–0.94) and with immunomodulator co-therapy (HR 0.77 95% CI: 0.61–0.97, p = 0.03).

Conclusion

This real-world data reflecting treatment effectiveness, tolerability and patient and prescriber preferences supports the use of UST and VDZ over anti-TNF agents in CD and UC, respectively, to achieve high treatment persistence which is independent of immunomodulator co-therapy, possibly secondary to differing immunogenicity rates. It also highlights the substantial increase in anti-TNF therapy persistence with thiopurine co-therapy, but not with methotrexate.

中文翻译：

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P361免疫调节剂和其他因素对克罗恩氏病和溃疡性结肠炎生物制剂持续性的影响：来自澳大利亚人口登记系统的数据

背景

治疗持续性（使用药物的持续时间）提供了有关治疗效果，耐受性以及处方者和患者偏好的现实证据。从没有分层处方顺序的全国人口登记处比较了克罗恩病（CD）和溃疡性结肠炎（UC）中生物制剂的持久性。我们假设免疫疗法共疗法会增加抗TNF药物的持久性，但由于降低的免疫原性不会增加非抗TNF药物的持久性。

方法

在2005年6月至2019年6月之间，从澳大利亚药物福利计划的前瞻性收集的基于人群的登记册中随机抽取了10％的亚组进行了分析。比较了阿达木单抗（ADA），英夫利昔单抗（IFX），维多珠单抗（VDZ）和乌斯替单抗（UST）的治疗持久性。使用多元比例风险回归评估影响停药的因素。

结果

纳入了886例患者，包括1294线疗法（992例CD，302例UC，2778人-年的随访）。在CD中，UST的总持续率最高（中位持续率> 74.6％，其中记录的最长随访时间为24.6个月），其次是VDZ，IFX和ADA（p = 0.03）（图1）。作为一线，二线和三线治疗，UST的持久性最高（p <0.05）。在UC中，VDZ的坚持率最高（中位数坚持率> 50.3％，其中记录的最长随访时间为47.4个月），其次是IFX和ADA（p <0.001）（图2）。VDZ作为一线治疗的持久性最高（p <0.001），而二线和三线治疗没有显着差异。：0.65 p <0.001）和UC（R ²：0.50 p <0.001）。硫嘌呤联合疗法可显着增加CD和UC中IFX和ADA的持久性（p <0.001）（图3和4），而对于UST和VDZ则无显着意义。甲氨蝶呤降低了UC中VDZ的持久性，并且对UC和CD中的UST，IFX和ADA无影响。在急性重度UC中，IFX作为单一疗法与联合疗法之间没有显着差异。在多变量分析中，男性（HR：0.75 95％CI：0.59–0.94）和免疫调节剂联合疗法的持久性更高。 HR 0.77 95％CI：0.61-0.97，p = 0.03）。

结论

反映治疗效果，耐受性以及患者和处方者偏好的真实数据支持UST和VDZ分别用于CD和UC中的抗TNF药物，以实现高治疗持久性，而与免疫调节剂联合疗法无关，可能是继发疗法不同的免疫原性率。它还强调了硫嘌呤联合疗法对抗TNF疗法持续性的显着提高，而甲氨蝶呤则没有。