Infliximab
(Synonyms: 英夫利昔单抗,Avakine; CT-P13) 目录号 : GC19533
英夫利昔单抗是一种嵌合单克隆 IgG1 抗体，可特异性结合 TNF-α。
Cas No.:170277-31-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
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Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
3T3L1 mature adipocytes |
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Preparation Method |
Adipocytes were stimulated twice at zero and 60 minutes with 2 μmol L 1 insulin. Adipocytes were stimulated with 10 ng/mL infliximab at the beginning of the 2-hour in vitro assay. 3T3L1 adipocytes were collected every 20 minutes for 2 hour. |
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Reaction Conditions |
10 ng/mL infliximab at the beginning of the 2-hour in vitro assay |
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Applications |
Infliximab restores insulin-dependent glucose uptake, phosphorylation of the insulin signaling pathway and attenuates TNF-alpha-induced PTP1B activation in TNF-α-treated 3T3L1 adipocytes. |
| Animal experiment [2]: | |
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Animal models |
Eight-week-old C57BL/6J (WT, TNF-α+/+) and TNF-α-deficient (TNFα−/−) mice of strain B6 |
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Preparation Method |
Infliximab was injected into diabetic and normal mice for 4 weeks |
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Dosage form |
Infliximab 10 μg/g in 100 μl saline for 4 weeks |
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Applications |
Diabetic mice showed significant impairments in SNCV and MNCV at 8 weeks. Diabetic mice treated with saline showed no improvement in SNCV or MNCV at 12 weeks, whereas diabetic mice treated with infliximab showed significant improvement at this time (4 weeks after infliximab treatment). |
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References: [1]. Méndez-García LA, Trejo-Millán F, Martínez-Reyes CP, Manjarrez-Reyna AN, Esquivel-Velázquez M, Melendez-Mier G, Islas-Andrade S, Rojas-Bernabé A, Kzhyshkowska J, Escobedo G. Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by attenuating PTP1B activation in 3T3L1 adipocytes in vitro. Scand J Immunol. 2018 Nov;88(5):e12716. doi: 10.1111/sji.12716. Epub 2018 Oct 10. PMID: 30260514. [2]. Yamakawa I, Kojima H, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998./p> |
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Infliximab is a chimeric monoclonal IgG1 antibody that specifically binds to TNF-α. Infliximab prevents the interaction of TNF-α with TNF-α receptor (TNFR1 and TNFR2). Infliximab has the potential for autoimmune, chronic inflammatory diseases and diabetic neuropathy research[1][2]. So, infliximab is a medication used to treat patients with autoimmune and chronic inflammatory diseases[5].
infliximab has been also shown to improve insulin resistance[3]. In vitro,infliximab ameliorates TNF-alpha-induced insulin resistance in 3T3L1 adipocytes in vitro by restoring phosphorylation of key mediators of the insulin signaling pathway such as IRS-2 and AKT via PTP1B inhibition that in consequence improves insulin-dependent glucose uptake in these adipose cells[4]
Diabetic mice showed significant impairments in SNCV and MNCV at 8 weeks. Diabetic mice treated with saline showed no improvement in SNCV or MNCV at 12 weeks, whereas diabetic mice treated with infliximab showed significant improvement at this time (4 weeks after infliximab treatment). In conclusion a single injection of infliximab leads to marked improvement in diabetic neuropathy[7].Infliximab reduces the levels of serum insulin, fasting glucose and insulin resistance in patients with ankylosing spondylitis and rheumatoid arthritis[6]
References:
[1]. Lis K, Kuzawińska O, et,al. Tumor necrosis factor inhibitors - state of knowledge. Arch Med Sci. 2014 Dec 22;10(6):1175-85. doi: 10.5114/aoms.2014.47827. PMID: 25624856; PMCID: PMC4296073.
[2]. Yamakawa I, Kojima H, Terashima T, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998.
[3]. Burska AN, Sakthiswary R, et,al. Effects of Tumour Necrosis Factor Antagonists on Insulin Sensitivity/Resistance in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. PLoS One. 2015 Jun 25;10(6):e0128889. doi: 10.1371/journal.pone.0128889. PMID: 26110878; PMCID: PMC4482317.
[4]. Méndez-García LA, Trejo-Millán F, et,al.Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by attenuating PTP1B activation in 3T3L1 adipocytes in vitro. Scand J Immunol. 2018 Nov;88(5):e12716. doi: 10.1111/sji.12716. Epub 2018 Oct 10. PMID: 30260514.
[5]. Antoni C, Krueger GG, et,al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005 Aug;64(8):1150-7. doi: 10.1136/ard.2004.032268. Epub 2005 Jan 27. PMID: 15677701; PMCID: PMC1755609.
[6]. Stagakis I, Bertsias G, et,al.Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther. 2012 Jun 12;14(3):R141. doi: 10.1186/ar3874. PMID: 22691241; PMCID: PMC3446524.
[7]. Yamakawa I, Kojima H, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998.
英夫利昔单抗是一种嵌合单克隆 IgG1 抗体,可特异性结合 TNF-α。英夫利昔单抗阻止 TNF-α 与 TNF-α 受体（TNFR1 和 TNFR2）的相互作用。英夫利昔单抗具有用于自身免疫、慢性炎症性疾病和糖尿病神经病变研究的潜力[1][2]。因此,英夫利昔单抗是一种用于治疗自身免疫性疾病和慢性炎症性疾病的药物[5]。
英夫利昔单抗也被证明可以改善胰岛素抵抗[3]。在体外,英夫利昔单抗通过 PTP1B 抑制恢复胰岛素信号通路关键介质（如 IRS-2 和 AKT）的磷酸化,从而改善这些脂肪细胞中胰岛素依赖性葡萄糖摄取,从而改善 3T3L1 脂肪细胞中 TNF-α 诱导的胰岛素抵抗细胞[4]
糖尿病小鼠在 8 周时显示 SNCV 和 MNCV 显着受损。用盐水治疗的糖尿病小鼠在 12 周时未显示 SNCV 或 MNCV 改善,而用英夫利昔单抗治疗的糖尿病小鼠此时显示出显着改善（英夫利昔单抗治疗后 4 周）。总之,单次注射英夫利昔单抗可显着改善糖尿病神经病变[7]。英夫利昔单抗可降低强直性脊柱炎和类风湿性关节炎患者的血清胰岛素、空腹血糖和胰岛素抵抗水平[ 6]
| Cas No. | 170277-31-3 | SDF | |
| 别名 | 英夫利昔单抗,Avakine; CT-P13 | ||
| 分子式 | C6428H9912N1694O1987S46 | 分子量 | 144188.23 |
| 溶解度 | 储存条件 | Store at -30°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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.0069 mL | 0.0347 mL | 0.0694 mL |
| 5 mM | 0.0014 mL | 0.0069 mL | 0.0139 mL |
| 10 mM | 0.0007 mL | 0.0035 mL | 0.0069 mL |
| 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。
Infliximab-Related Infusion Reactions: Systematic Review
Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms.
Clinical Pharmacokinetics and Pharmacodynamics of Infliximab in the Treatment of Inflammatory Bowel Disease
Infliximab was the first monoclonal antibody to be approved for the treatment of pediatric and adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC). It has been shown to induce and maintain both clinical remission and mucosal healing in pediatric and adult patients with inflammatory bowel disease (IBD) who are unresponsive or refractory to conventional therapies. The administration of infliximab is weight-based and the drug is administered intravenously. The volume of distribution of infliximab is low and at steady state ranges from 4.5 to 6 L. Therapeutic monoclonal antibodies, such as immunoglobulins, are cleared from the circulation primarily by catabolism. Median infliximab half-life is approximately 14 days. Infliximab concentration-time data in patients with CD and UC have been shown to be highly variable within an individual patient over time and between individuals by multiple population pharmacokinetic models. Covariates that have been identified to account for a part of the observed inter- and intra-individual variability in clearance are the presence of antidrug antibodies, use of concomitant immunomodulators, degree of systemic inflammation, serum albumin concentration, and body weight, which can affect the pharmacodynamic response. This article provides a comprehensive review of the clinical pharmacokinetics and pharmacodynamics of infliximab, as well as the role of therapeutic drug monitoring in the treatment of IBD.
Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial
Importance: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy.
Objective: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM.
Design, setting, and participants: Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020.
Interventions: Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230).
Main outcome and measures: The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period.
Results: Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively.
Conclusions and relevance: Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach.
Trial registration: ClinicalTrials.gov Identifier: NCT03074656.
Infliximab and biosimilar infliximab in psoriasis: efficacy, loss of efficacy, and adverse events
Psoriasis is a chronic immune-mediated skin disease affecting multiple systems, and tumor necrosis factor-α (TNF-α) plays a significant role in the initiation and progression of the disease process. Psoriasis has a high prevalence rate in the Western world, especially in the USA and Australia; in China, although the prevalence rate is much lower, there is still a large number of patients suffering from psoriasis and its comorbidities. As TNF-α is thought to be crucial in the pathogenesis of psoriasis, specific therapy blocking TNF-α may be beneficial in the treatment of this disease. Infliximab, a murine-human monoclonal antibody, is highly efficacious in the treatment of moderate-to-severe psoriasis, with better skin clearance and faster onset of action than topical medications such as methotrexate, narrow-band ultraviolet B, and calcipotriol. Lack of adherence to infliximab therapy is mainly due to loss of response (LOR) over time and adverse events, particularly because infusion reactions are usually encountered. Anti-infliximab antibody is thought to be responsible for the LOR and infusion reactions. However, the mechanism underlying the formation of anti-infliximab antibody and its side effects remains unclear. Further studies identifying patients at risk for LOR will probably help clinicians to select the right patients for anti-TNF-α therapy and to increase the durability of the treatment. This review discusses the efficacy of infliximab as demonstrated by various clinical trials, LOR to infliximab, combatting LOR, as well as the adverse events usually faced during the use of infliximab therapy and the infliximab biosimilar Remsima?. We hope that we can discover a better way to use infliximab in the therapy of psoriasis from the current research data.
Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial
Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear.
Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM.
Design, setting, and participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019.
Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204).
Main outcomes and measures: The primary end point was clinical remission at week 30.
Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively.
Conclusions and relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates.
Trial registration: ClinicalTrials.gov Identifier: NCT03074656.