Etrolizumab
(Synonyms: rhuMAb Beta7; RG7413; PRO145223) 目录号 : GC68283Etrolizumab (rhuMAb Beta7) 是一种肠道选择性抗-β7 整合素单克隆抗体。Etrolizuma b是针对 α4β7 和 αEβ7 整合素的 β7 亚基的特异性靶向药物。Etrolizumab 可用于炎症性肠病 (IBD) 的研究。
Cas No.:1044758-60-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Etrolizumab (rhuMAb Beta7) is a gut-selective, anti-β7 integrin monoclonal antibody. Etrolizumab is specific targeting of the β7 subunit of α4β7 and αEβ7 integrins with Ki values of 18 nM and 1800 pM for Human α4β7 and Human αEβ7-293, respectively. Etrolizumab can be used in research of inflammatory bowel disease (IBD)[1][2].
Etrolizumab (rhuMAb Beta7) binds the β7 subunit of both α4β7 and αEβ7 integrins with high affinity, with Kd values of 18 nM, 1800 pM, 181 pM, 116 pM, 57 pM, 31.7 pM, and 25.7 pM for Human α4β7, Human αEβ7-293, Mouse α4β7-38C13, Human α4β7-293, Rabbit PBLs, Human PBLs, and Cyno PBLs, respectively[1].
Etrolizumab (RPMI 8866 cells and αEβ7-293 cells) blocks the interaction of α4β7 with its cognate ligands MAdCAM-1 and VCAM-1 with IC50 values of 0.075 and 0.089 nM, respectively, and blocks the interaction between αEβ7 and its ligand E-cadherin with an IC50 value of 3.96 nM[1].
Etrolizumab (rhuMAb Beta7; 5 mg/kg; i.v.; once; normal female BALB/c mice) decreases β7 integrins on T lymphocytes[2].
Etrolizumab (200 µg (100 µL); i.p.; once) inhibits lymphocyte homing in the CD45RBhigh T cell-reconstituted SCID mouse model of colitis[2].
| Animal Model: | Normal female BALB/c mice (17-21 g)[2] |
| Dosage: | 5 mg/kg |
| Administration: | Intravenous injection; once |
| Result: | Had 98.3% of intraepithelial CD8+ T-cell β7 integrin receptors and 90.0% of intraepithelial CD4+ T-cell β7 integrin receptors after 24 h. |
| Animal Model: | SCID mouse model of colitis[2] |
| Dosage: | 200 µg (100 µL) |
| Administration: | Intraperitoneal injection; once |
| Result: | Blocked lymphocyte recruitment and homing to the inflamed colon. |
[1]. Tang MT, et, al. Review article: nonclinical and clinical pharmacology, pharmacokinetics and pharmacodynamics of etrolizumab, an anti-β7 integrin therapy for inflammatory bowel disease. Aliment Pharmacol Ther. 2018 Jun;47(11):1440-1452.
[2]. Stefanich EG, et, al. A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes. Br J Pharmacol. 2011 Apr;162(8):1855-70.
| Cas No. | 1044758-60-2 | SDF | Download SDF |
| 别名 | rhuMAb Beta7; RG7413; PRO145223 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study
Lancet Gastroenterol Hepatol 2022 Feb;7(2):118-127.PMID:34798038DOI:10.1016/S2468-1253(21)00294-6.
Background: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, Etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of Etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. Methods: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous Etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of Etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. Findings: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to Etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the Etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the Etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the Etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the Etrolizumab group and 43 [22%] in the infliximab group). More patients in the Etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. Interpretation: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, Etrolizumab performed similarly to infliximab from a clinical viewpoint. Funding: F Hoffmann-La Roche.
Etrolizumab for ulcerative colitis: the new kid on the block?
Expert Opin Biol Ther 2016;16(4):567-72.PMID:26914639DOI:10.1517/14712598.2016.1158807.
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Currently approved therapies include prednisone, TNF antagonists and anti-metabolites which often are ineffective and have frequent adverse effects. Consequently, UC patients are always at risk for developing serious complications that affect their quality of life. Therefore, new treatment options are required. Areas covered: This article discusses Etrolizumab, its mechanism and the potential role it can have in the future of treating UC. Etrolizumab is a humanized monoclonal antibody that selectively blocks lymphocyte trafficking and retention in the gut. The safety and efficacy data was reviewed from all randomized placebo-controlled trials which evaluated Etrolizumab for the treatment of UC. Expert opinion: Etrolizumab is an effective and well-tolerated drug for the treatment of UC. It appears to be a promising molecule that can benefit UC patients.
Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis
Lancet Gastroenterol Hepatol 2022 Feb;7(2):161-170.PMID:34856198DOI:10.1016/S2468-1253(21)00377-0.
Background: There is a growing armamentarium for the treatment of moderate-to-severe ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics and small molecule drugs for the treatment of patients with moderate-to-severe ulcerative colitis. Methods: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions for articles published between Jan 1, 1990, and July 1, 2021. Major congresses' databases from Jan 1, 2018, to July 3, 2021, were reviewed manually. Phase 3, placebo-controlled or head-to-head randomised controlled trials (RCTs) assessing the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for patients with moderate-to-severe ulcerative colitis were included. Phase 2 RCTs were excluded because of their small sample sizes and inclusion of doses not further explored in phase 3 RCTs. Summary data from intention-to-treat analyses were extracted from included reports by JSL and PAO. The primary outcome was the induction of clinical remission. A network meta-analysis was done under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. The surface under the cumulative ranking (SUCRA) was used to rank the included agents for each outcome. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. Maintenance data on efficacy for treat-straight-through and randomised responder trials are also presented. This study is registered with PROSPERO, CRD42021225329. Findings: Our search yielded 5904 results, from which 29 studies (four being head-to-head RCTs) fulfilled our inclusion criteria and were included. Of these, 23 studies assessed induction therapy with either a biologic or small molecule drug, comprising 10 061 patients with ulcerative colitis. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission (infliximab [OR 2·70, 95% CI 1·18-6·20], adalimumab [4·64, 2·47-8·71], golimumab [3·00, 1·32-6·82], vedolizumab [3·56, 1·84-6·91], ustekinumab [2·92, 1·31-6·51], Etrolizumab [4·91, 2·59-9·31], tofacitinib [2·84, 1·28-6·31], filgotinib 100 mg [6·15, 2·98-12·72], filgotinib 200 mg [4·49, 2·18-9·24], and ozanimod (2·70, 1·18-6·20), and ranked highest for the induction of clinical remission (SUCRA 0·996). No differences between active interventions were observed when assessing adverse events and serious adverse events. Vedolizumab ranked lowest for both adverse events (SUCRA 0·184) and serious adverse events (0·139), whereas upadacitinib ranked highest for adverse events (0·843) and ozanimod ranked highest for serious adverse events (0·831). Interpretation: Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent in terms of adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes. With the paucity of direct comparisons in the published literature, our results might help clinicians to position drugs in treatment algorithms. Funding: None.
Vedolizumab and Etrolizumab for ulcerative colitis: twins or simple cousins?
Expert Opin Biol Ther 2020 Apr;20(4):353-361.PMID:31951748DOI:10.1080/14712598.2020.1717465.
Introduction: Vedolizumab is a monoclonal antibody that selectively blocks α4β7 integrin and has already been approved for use in patients with moderate-to-severe ulcerative colitis both as first and second line. Etrolizumab is a monoclonal antibody still being tested, which acts with a dual mechanism by selectively inhibiting both α4β7 and αEβ7 integrins.Areas covered: This review provides an overview of the literature data of vedolizumab and Etrolizumab, in order to define their role in the treatment of patients with moderate-to-severe ulcerative colitis.Expert opinion: Etrolizumab and vedolizumab block the α4β7 integrin with a similar action mechanism. However, the inhibition of αEβ7 integrin by Etrolizumab distinguishes the two anti-integrins making them 'cousin' drugs. Phase 3 clinical trials are needed to confirm the promising Etrolizumab's efficacy data and to resolve any doubts about its safety, allowing a clearer comparison with vedolizumab.
Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial
Lancet Gastroenterol Hepatol 2022 Feb;7(2):128-140.PMID:34798039DOI:10.1016/S2468-1253(21)00298-3.
Background: Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, Etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of Etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods: HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label Etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous Etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to Etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous Etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. Findings: HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (Etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (Etrolizumab to Etrolizumab n=117, Etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the Etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between Etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the Etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (Etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (Etrolizumab to Etrolizumab 98 [88%] of 112; Etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (Etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the Etrolizumab to Etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the Etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation: HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with Etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding: F Hoffmann-La Roche.