interleukin inhibitor

白细胞介素抑制剂
  • 文章类型: Journal Article
    背景:炎症性肠病(IBD)患者的感染风险增加。这项研究的目的是评估使用白介素(IL)靶向药物治疗的IBD患者的累积发病率和感染风险。
    方法:我们搜索了PubMed,EMBASE,和WebofScience的随机对照试验,包括接受IL靶向药物的IBD患者与接受安慰剂或治疗的患者相比,仅在没有IL靶向药物的情况下与干预组不同。感兴趣的主要结果是诱导阶段任何级别和严重感染的相对风险(RR)。
    结果:任何等级的风险均无差异(RR,0.98;95%置信区间[CI],0.89-1.09)或严重(RR,0.64;95%CI,0.38-1.10)与对照组相比,接受任何IL靶向剂的患者感染。在维护期间,接受IL-12/23p40靶向药物(平均随访29周)的患者中任何级别感染的累积发生率为34.82%(95%CI,26.78%-43.32%),而严重感染的累积发生率为3.07%(95%CI,0.93%-6.21%)。接受IL-23p19靶向药物(平均随访40.9周)的患者中任何级别感染的累积发生率为32.16%(95%CI,20.63%-44.88%),而严重感染的累积发生率为1.75%(95%CI,0.60%-3.36%)。在纳入研究的维持阶段,对照组中任何级别的感染发生率为30.66%(95%CI,22.12%-39.90%),严重感染发生率为1.59%(95%CI,0.76%-2.63%)。
    结论:与对照组相比,接受IL靶向药物的IBD患者的感染风险没有差异。报告IL抑制剂安全性的病例登记册和随机对照试验应提供有关接受IL靶向药物的IBD患者特定感染并发症风险的详细信息。
    与接受安慰剂或缺乏白介素靶向剂治疗的炎症性肠病患者相比,接受白介素靶向剂治疗的炎症性肠病患者不太可能发生任何级别或严重感染。
    BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents.
    METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase.
    RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group.
    CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.
    Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    未经批准:本研究旨在比较开始使用阿普司特的银屑病患者的治疗模式和医疗费用,肿瘤坏死因子抑制剂,或者白介素抑制剂.
    UNASSIGNED:这项回顾性队列研究使用OptumClinformatics®DataMart来识别倾向评分匹配的患者,肿瘤坏死因子抑制剂,或者白细胞介素抑制剂,12个月基线和24个月随访数据。开关,停药,持久性,医疗保健资源利用,并评估了医疗总费用。
    未经评估:肿瘤坏死因子抑制剂的24个月转换率最高(32%),其次是apremilast(21%),然后是白介素抑制剂(14%)。转换者的平均(SD)每位患者每月的费用最低($4213[$2304]),更高的肿瘤坏死因子抑制剂($5274[$2280]),白细胞介素抑制剂最高(5539美元[2296美元];P<0.001),主要归因于药房费用:3466美元(apremilast),$4432(肿瘤坏死因子抑制剂),和$4721(白介素抑制剂)。
    UNASSIGNED: This study aimed to compare treatment patterns and healthcare costs for patients with psoriasis who initiate apremilast, tumor necrosis factor inhibitor, or interleukin inhibitor.
    UNASSIGNED: This retrospective cohort study used Optum Clinformatics® Data Mart to identify propensity score-matched patients initiating apremilast, tumor necrosis factor inhibitors, or interleukin inhibitors, with 12-month baseline and 24-month follow-up data. Switch, discontinuation, persistence, healthcare resource utilization, and total healthcare costs were assessed.
    UNASSIGNED: Twenty-four-month switch rates were highest for tumor necrosis factor inhibitors (32%), followed by apremilast (21%) then interleukin inhibitors (14%). Mean (SD) per-patient-per-month costs for switchers were lowest for apremilast ($4213 [$2304]), higher for tumor necrosis factor inhibitors ($5274 [$2280]), and highest for interleukin inhibitors ($5539 [$2296]; p < .001), primarily attributable to pharmacy costs: $3466 (apremilast), $4432 (tumor necrosis factor inhibitor), and $4721 (interleukin inhibitor).
    UNASSIGNED: Psoriasis severity is absent from claims data; cost outcomes may be influenced by more severe psoriasis being more costly.
    UNASSIGNED: Switching psoriasis treatment is common and increases over time. Apremilast initiators had lower switch rates and costs compared with tumor necrosis factor inhibitors, despite lower effectiveness reported in previous studies, perhaps indicating patient preference for oral treatment. Additional oral options may be desirable for this population.
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  • 文章类型: Journal Article
    UNASSIGNED:通过随机对照试验(RCT)进行的头对头比较提供了高质量的证据来指导医疗保健决策。在他们缺席的时候,经常进行间接比较;然而,关于基于匹配调整间接比较(MAIC)的有效比较疗效估计值与基于RCT的估计。
    未经评估:比较guselkumab的MAIC和RCT结果与苏金单抗和ixekizumab,以深入了解使用MAIC方法产生的结果的有效性。
    UNASSIGNED:先前报道的来自guselkumab与MAIC的结果根据银屑病面积和严重程度指数(PASI)90应答率之间的风险差异,将苏金单抗和ixekizumab与ECLIPSE和IXORA-RRCTs的结果进行了比较.
    UNASSIGNED:guselkumab与48周时PASI90反应率的风险差异(95%置信区间)苏金单抗在ECLIPSE和MAIC中分别为14.4%(9.4%;19.4%)和9.4%(4.7%;14.0%).guselkumab与第24周的风险差异IXORA-R中的ixekizumab为0.0%(-5.4%;5.4%),MAIC中的ixekizumab为0.7%(-5.1%;6.4%)。
    UNASSIGNED:guselkumab与MAIC和RCT之间的比较疗效结果一致苏金单抗和ixekizumab。此分析表明,当缺乏直接比较时,MAIC方法可以提供有效的相对治疗效果估计,特别是当具有相似设计和患者群体的试验为分析提供信息时.
    UNASSIGNED: Head-to-head comparisons through randomized controlled trials (RCTs) provide high-quality evidence to inform healthcare decisions. In their absence, indirect comparisons are often performed; however, evidence is limited on how valid matching-adjusted indirect comparison (MAIC)-based comparative efficacy estimates are vs. RCT-based estimates.
    UNASSIGNED: Compare MAIC and RCT results of guselkumab vs. secukinumab and ixekizumab to provide insight into the validity of results generated using MAIC methods.
    UNASSIGNED: Previously reported results from MAICs of guselkumab vs. secukinumab and ixekizumab were compared with results from ECLIPSE and IXORA-R RCTs based on risk differences between Psoriasis Area and Severity Index (PASI) 90 response rates.
    UNASSIGNED: Risk difference (95% confidence interval) in PASI 90 response rates at week 48 for guselkumab vs. secukinumab was 14.4% (9.4%; 19.4%) in ECLIPSE and 9.4% (4.7%; 14.0%) in the MAIC. The risk difference at week 24 for guselkumab vs. ixekizumab was 0.0% (-5.4%; 5.4%) in IXORA-R and 0.7% (-5.1%; 6.4%) in the MAIC.
    UNASSIGNED: Comparative efficacy results were consistent between MAICs and RCTs of guselkumab vs. secukinumab and ixekizumab. This analysis demonstrates that MAIC methods can provide valid relative treatment effect estimates when direct comparisons are lacking, particularly when trials with similar designs and patient populations inform the analysis.
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  • 文章类型: Journal Article
    未经证实:白细胞介素(IL)抑制剂比旧的全身疗法获得更高的疗效。我们计算了ixekizumab与意大利批准用于治疗中度至重度斑块状银屑病的其他IL抑制剂相比所需的治疗数量(NNT)。
    未经批准:根据NNT评估临床疗效,基于Cochrane系统评价数据库最近的网络元分析(NMA)的结果。NMA调查了许多系统和生物治疗,但这项分析仅比较了以下IL抑制剂的疗效-brodalumab,guselkumab,ixekizumab,risankizumab,苏金单抗,tildrakizumab和ustekinumab-用于中度至重度斑块状银屑病患者。考虑到PASI(银屑病面积和严重程度指数)90评分,根据有效性对药物进行比较和排序。
    UNASSIGNED:在NMA中纳入了一百四十项试验(51,749例患者)。考虑到达到PASI90的患者比例,ixekizumab在所有比较中显示出最低的NNT(ixekizumab2.01[2.46-3.00];risankizumab2.05[2.50-3-05];guselkumab2.16[2.68-3.36];苏金单抗2.40[2.90-3.51];brodalumab
    UNASSIGNED:研究结果表明,ixekizumab是治疗中度至重度斑块状银屑病的最有效选择(NNT)。
    UNASSIGNED: Interleukin (IL) inhibitors achieve greater levels of efficacy than older systemic therapies. We calculated the number needed to treat (NNT) of ixekizumab compared with other IL inhibitors approved in Italy for the treatment of moderate-to-severe plaque psoriasis.
    UNASSIGNED: The clinical efficacy was evaluated in terms of NNT, based on the results of a recent network meta--analysis (NMA) by the Cochrane Database of Systematic Reviews. The NMA investigated many systemic and biological treatments, but this analysis compared only the efficacy of the following IL inhibitors - brodalumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab - for patients with moderate-to-severe plaque psoriasis. Drugs were compared and ranked according to effectiveness considering the PASI (Psoriasis Area and Severity Index) 90 score.
    UNASSIGNED: One-hundred and forty trials (51,749 patients) were included in the NMA. Considering the proportion of patients who achieve PASI90, ixekizumab showed the lowest NNT among all comparators (ixekizumab 2.01 [2.46-3.00]; risankizumab 2.05 [2.50-3-05]; guselkumab 2.16 [2.68-3.36]; secukinumab 2.40 [2.90-3.51]; brodalumab 2.61 [3.18-3.88]; ustekinumab 3.44 [4.12-4.95]; tildrakizumab 3.10 [4.15-5.59].
    UNASSIGNED: The findings show that ixekizumab is the most effective option (NNT) for the treatment of moderate-to-severe plaque psoriasis.
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  • 文章类型: Journal Article
    难治性复发性口疮性口炎(RRAS)表现为口腔粘膜严重溃疡性病变,愈合不良,对常规治疗反应不良,有或没有全身性疾病。由于缺乏有效的治疗方法,其治疗仍然是临床挑战。最近,生物制剂已成为RRAS的有希望的靶向疗法。靶向特定炎症通路的生物制剂参与RRAS的发病机理,包括肿瘤坏死因子-α抑制剂和白细胞介素抑制剂,为RRAS提供更精确和有前途的治疗方法。这些靶向治疗已被证明可以促进愈合并减少复发频率,提高RRAS患者的生活质量。在这里,综述了目前用于治疗RRAS的生物制剂的类型和机制;此外,剂量,持续时间,治疗效果,以及有或没有某些相关全身性疾病的RRAS的不良反应,并讨论了当前的问题和未来的方向。
    Refractory recurrent aphthous stomatitis (RRAS) manifests as severe ulcerative lesions of the oral mucosa with poor healing and a poor response to conventional therapy, with or without systemic diseases. Its treatment remains a clinical challenge owing to the lack of effective therapies. Recently, biologics have emerged as promising targeted therapies for RRAS. The biologics targeting specific inflammatory pathways involved in the pathogenesis of RRAS, including tumor necrosis factor-alpha inhibitors and interleukin inhibitors, offer a more precise and promising therapeutic approach for RRAS. These targeted therapies have been shown to promote healing and decrease recurrence frequency in, and improve the quality of life of patients with RRAS. Herein, the types and mechanisms of biologics currently used to treat RRAS have been reviewed; furthermore, the dose, duration, therapeutic efficacy, and adverse effects of RRAS with or without certain associated systemic diseases, and the current problems and future directions have been discussed.
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  • 文章类型: Journal Article
    背景:迄今为止,只有糖皮质激素和白细胞介素-6(IL-6)抑制剂被证明可以降低COVID-19住院患者的死亡率.在这篇文献综述中,我们的目的是总结IL抑制剂的感染风险,无论是否使用皮质类固醇,用于治疗COVID-19住院患者。
    方法:使用以下循证医学综述进行了文献检索:Cochrane中央对照试验注册;Cochrane系统综述数据库;Embase;OvidMedline和EpubAheadofPrint,在过程中,数据审查和其他非索引引文,每日和版本1946年至2021年4月28日。所有相关文章都是使用搜索词COVID-19或SARS-冠状病毒-2,感染,白细胞介素,住院病人,成年人,我相信。
    结果:我们确定了36项研究,其中2项是荟萃分析,5个是随机对照试验,9是前瞻性研究,20项为回顾性研究.当阿纳金拉与对照相比时,2项研究报告感染风险增加,3项研究报告了相似或降低的感染发生率。在一项研究中,与安慰剂相比,Canakinumab的相关感染发生率较低。当sarilumab与安慰剂比较时,一项研究报告感染风险增加.九项比较托珠单抗与安慰剂的研究报告了感染风险降低或无差异(研究的比值比[OR]为0.39-1.21)。14项比较托珠单抗与安慰剂的研究报告了感染风险增加,范围为9.1%至63.0%(研究的OR范围为1.85-5.04)。感染最常表现为菌血症。在比较托珠单抗和皮质类固醇与安慰剂的6项研究中,4报告了与细菌感染相关的皮质类固醇的无显著增加(OR范围为2.76-3.8),2项研究报告未增加感染风险.
    结论:我们的文献综述显示,IL-6抑制剂与COVID-19患者感染风险的相关性具有不同意义。
    BACKGROUND: To date, only corticosteroids and interleukin-6 (IL-6) inhibitors have been shown to reduce mortality of hospitalized patients with COVID-19. In this literature review, we aimed to summarize infection risk of IL inhibitors, with or without the use of corticosteroids, used to treat hospitalized patients with COVID-19.
    METHODS: A literature search was conducted using the following evidence-based medicine reviews: Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; Embase; Ovid Medline; and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions 1946 to April 28, 2021. All relevant articles were identified using the search terms COVID-19 or SARS-coronavirus-2, infections, interleukins, inpatients, adults, and i ncidence.
    RESULTS: We identified 36 studies of which 2 were meta-analyses, 5 were randomized controlled trials, 9 were prospective studies, and 20 were retrospective studies. When anakinra was compared with control, 2 studies reported an increased risk of infection, and 3 studies reported a similar or decreased incidence of infection. Canakinumab had a lower associated incidence of infection compared with placebo in one study. When sarilumab was compared with placebo, one study reported an increased risk of infection. Nine studies comparing tocilizumab with placebo reported decreased or no difference in infection risk (odds ratio [OR] for the studies ranged from 0.39-1.21). Fourteen studies comparing tocilizumab with placebo reported an increased risk of infection, ranging from 9.1% to 63.0% (OR for the studies ranged from 1.85-5.04). Infection most commonly presented as bacteremia. Of the 6 studies comparing tocilizumab and corticosteroid use with placebo, 4 reported a nonsignificant increase toward corticosteroids being associated with bacterial infections (OR ranged from 2.76-3.8), and 2 studies reported no increased association with a higher infection risk.
    CONCLUSIONS: Our literature review showed mixed results with variable significance for the association of IL-6 inhibitors with risk of infections in patients with COVID-19.
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  • 文章类型: Journal Article
    Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed.
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