在先前已转换治疗的炎症性肠病患者中，从生物类似药SB2反向转换为原研英夫利昔单抗：一项前瞻性长期队列研究的结果
Reverse switching from the biosimilar SB2 to the originator infliximab in previously switched patients with inflammatory bowel diseases: results of a prospective long-term cohort study.
作者信息
Fischer Sarah, Donhauser Moritz, Cohnen Sarah, Fietkau Konstantin, Vetter Marcel, Grübel-Liehr Maria, Dietrich Peter, Rath Timo, Wilfer Angelika, Sologub Ludmilla, Krebs Sabine, Dörje Frank, Nagore Daniel, Meyer Sebastian, Neurath Markus F, Atreya Raja
机构信息
First Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Deutsches Zentrum Immuntherapie, Erlangen, Germany.
Deutsches Zentrum Immuntherapie, Erlangen, Germany.
出版信息
Therap Adv Gastroenterol. 2024 Nov 30;17:17562848241301887. doi: 10.1177/17562848241301887. eCollection 2024.
BACKGROUND
Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD).
OBJECTIVES
We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence.
DESIGN
This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96 weeks and followed up for another 48 weeks.
METHODS
Clinical disease activity (Harvey-Bradshaw-index (HBI) in Crohn's disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study.
RESULTS
Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1-4) at baseline and 2 (1-4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0-1) at baseline and 0.5 (0-1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0 mg/l (IQR 1.0-4.1) at baseline and 2.4 mg/l (1.1-5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD ( = 0.3) and UC ( = 0.9). Median TL were 7.2 µg/ml (IQR 3.8-19.3) at baseline and 5.5 µg/ml (3.5-13.1) at week 48, resulting in a mean change of -1.0 (SD 7.4) with no statistical significance (CD = 0.26, UC = 0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies.
CONCLUSION
Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn't influence immunogenicity or safety of therapy.
背景
在炎症性肠病（IBD）领域，关于包括英夫利昔单抗与其生物类似药之间反向转换在内的多次转换的数据很少。
目的
我们将重复转换后的临床疗效作为主要结局指标进行了研究。次要终点包括C反应蛋白（CRP）水平、免疫原性（谷浓度（TL）；抗药物抗体（ADA））、安全性和药物持久性。
设计
本研究是一项前瞻性、单中心、观察性队列研究。接受原研英夫利昔单抗治疗的IBD患者被转换为生物类似药SB2，96周后进行反向转换，并再随访48周。
方法
在整个研究过程中监测临床疾病活动度（克罗恩病（CD）中的哈维 - 布拉德肖指数（HBI），溃疡性结肠炎（UC）中的部分梅奥评分（pMS））、CRP、TL、ADA、治疗中断情况和（严重）不良事件（（S）AE）。
结果
共纳入95例患者（60例CD，38例女性）。基线时HBI中位数为2（四分位间距（IQR）1 - 4），48周时为2（1 - 4），个体内平均变化为0.0（标准差（SD）1.5）。基线时pMS中位数为1（IQR 0 - 1），48周时为0.5（0 - 1），个体内平均变化为0.0（SD 0.8）。基线时80%的患者达到临床缓解，48周时为82%。基线时CRP中位数为2.0mg/l（IQR 1.0 - 4.1），48周时为2.4mg/l（1.1 - 5.2），平均变化为1.7（SD 5.8），在CD（P = 0.3）和UC（P = 0.9）中无显著差异。基线时TL中位数为7.2μg/ml（IQR 3.8 - 19.3），48周时为5.5μg/ml（3.5 - 13.1），平均变化为 - 1.0（SD 7.4），无统计学意义（CD P = 0.26，UC P = 0.41）。3.4%的患者产生了新的ADA。停药率为14.7%。安全信号与既往研究一致。
结论
在我们的IBD患者队列中，反向转换对英夫利昔单抗治疗的疗效没有影响。转换未影响治疗的免疫原性或安全性。
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