Spesolimab

来源：Pharmacoepidemiology and Drug Safety (Pharmacoepidemiol Drug Saf) 医院药学研究 第5期（ 总第25期） 本期聚焦药物流行病学与用药安全领域的最新研究成果，涵盖大规模药物性肝损伤住院风险的筛查、真实世界中直接口服抗凝药的出血风险比较、质子泵抑制剂长期使用的安全性评估、多药联用与药物相互作用的不良结局分析以及处方级联的识别与管理等与医院药学安全实践密切相关的原创研究与系统评价。 ◆ 论文目录（中英对照） 1. [Original Research] High-Throughput Screening Using the Self-Controlled Tree-Based Scan Statistic to Identify Medications Associated With Hospitalization for Severe Acute Liver Injury 采用自身对照树状扫描统计方法高通量筛选与严重急性肝损伤住院相关的药物 2. [Original Research] Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using the Clinical Practice Research Datalink (CPRD) 使用临床实践研究数据库的自体对照病例序列联合活性对照方法在药物安全信号检测中的性能评价 3. [Original Research] Predictors of Direct Oral Anticoagulant Use in Northern Italy: A Population-Based Study 北意大利直接口服抗凝药使用的预测因素：一项基于人群的研究 4. [Original Research] Measuring Exposure to Opioids Using Self-Reported Medication Use Data Versus General Practitioner Prescription Records in the UK Biobank Study 英国生物银行研究中自我报告用药数据与全科医师处方记录在阿片类药物暴露测量中的比较 5. [Systematic Review] Efficacy and Safety of All Monoclonal Antibodies in Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis 单克隆抗体治疗中重度特应性皮炎的疗效与安全性：系统综述与网络荟萃分析 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎Original Research High-Throughput Screening Using the Self-Controlled Tree-Based Scan Statistic to Identify Medications Associated With Hospitalization for Severe Acute Liver Injury Pharmacoepidemiol Drug Saf 丨 2025-12-XX 丨 Original Research ▍采用自身对照树状扫描统计方法高通量筛选与严重急性肝损伤住院相关的药物 研究背景 药物性肝损伤（DILI）是导致药物撤市和药物相关住院的重要原因之一。传统上，肝毒性信号主要通过病例报告来识别，存在滞后性和低敏感性等局限。随着真实世界数据（RWD）的广泛应用，高通量筛查方法为早期识别潜在的肝毒性药物提供了新的可能。树状扫描统计方法（TreeScan）是一种数据驱动的主动监测方法，可在无预设假设的情况下同时筛查大量药物-不良事件关联。本研究利用美国退伍军人健康管理局（VHA）数据库，采用自身对照病例交叉设计，系统评估了TreeScan在无肝胆疾病患者和慢性肝病患者中识别严重急性肝损伤相关药物的性能，为医院药物安全管理提供了重要的方法学参考和临床证据。 核心发现 • 在12,860名无肝胆疾病和17,512名慢性肝病住院严重ALI患者中，分别评估了与450种和543种药物的潜在关联 • 无明显肝病患者中，雷尼替丁、奥美拉唑、昂丹司琼等药物与严重ALI显著相关；慢性肝病患者中，螺内酯、呋塞米、多种阿片类镇痛药和昂丹司琼等均与严重ALI显著相关 • 抗菌药物（阿莫西林/克拉维酸、环丙沙星、甲硝唑等）在两类患者中均显示出肝毒性信号 • 树状扫描统计方法作为一种高通量筛查工具，能够有效检测潜在肝毒性药物，为后续药物流行病学研究提供候选药物 领域意义 本研究为医院药学实践提供了重要的药物肝毒性风险信息。研究识别出的一系列可能与严重急性肝损伤相关的药物，涵盖了医院常用药如质子泵抑制剂（奥美拉唑）、止吐药（昂丹司琼）、利尿剂（螺内酯、呋塞米）和抗菌药物等，提醒医院药师在处方审核和药学监护中需特别关注这些药物的肝毒性风险。基于TreeScan的高通量筛查方法为医院建立主动式药物安全监测体系提供了新思路。对于已有肝病基础的患者群体，研究结果强调了更严格用药管理的重要性，有助于医院药学部门优化肝病患者用药方案。 英文摘要 (Abstract) Background: Medications associated with acute liver injury (ALI) are primarily identified by case reports. High-throughput screening of real-world data could be leveraged to detect hepatotoxicity signals. Objective: To apply tree-based scan statistics in real-world data to identify drugs associated with hospitalization for severe ALI among patients without liver/biliary disease and with chronic liver disease (CLD). Methods: We implemented a self-controlled case-crossover design in Veterans Health Administration data (2000-2023) among patients hospitalized for laboratory-confirmed severe ALI. We identified all newly dispensed drugs within 365 days prior to their hospitalization and used conditional Bernoulli tree-based scan statistics to identify potential associations (p < 0.3). We performed analyses separately in patients without liver/biliary disease and with CLD. Results: Among 12,860 patients without liver/biliary disease and 17,512 with CLD hospitalized for severe ALI, we evaluated associations with 450 and 543 drugs, respectively. Drugs associated with severe ALI among patients without liver/biliary disease included: acid-suppressives (ranitidine [p < 0.001], omeprazole [p = 0.004]), antiemetics (ondansetron [p < 0.001], promethazine [p = 0.06]), antibiotics (amoxicillin/clavulanate [p = 0.008], ciprofloxacin [p = 0.02], mupirocin [p = 0.032], ethambutol [p = 0.275]), anticoagulants (heparin [p = 0.015]), and chemotherapy (pazopanib [p = 0.275]). Drugs associated with severe ALI among CLD patients were: diuretics (spironolactone, furosemide [both p < 0.001]), antiemetics (ondansetron, metoclopramide, promethazine [all p < 0.001]), appetite stimulants (p < 0.001), analgesics (morphine, oxycodone, fentanyl [all p < 0.001]), chemotherapy (sorafenib [p < 0.001]), antibiotics (ciprofloxacin [p = 0.011], metronidazole [p = 0.020]), antipsychotics (prochlorperazine [p = 0.105]), vitamins (p = 0.134), acid-suppressives (omeprazole [p = 0.164]), and gastrointestinal/liver disease treatments (lactulose, senna, docusate, silicones, antiflatulents [all p < 0.001]; sucralfate [p = 0.005], albumin [p = 0.228]). Conclusions: High-throughput screening using tree-based scan statistics detected potentially hepatotoxic drugs for investigation in future pharmacoepidemiology studies. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎Original Research Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using the Clinical Practice Research Datalink (CPRD) Pharmacoepidemiol Drug Saf 丨 2025-12-XX 丨 Original Research ▍使用临床实践研究数据库的自体对照病例序列联合活性对照方法在药物安全信号检测中的性能评价 研究背景 药物安全信号检测是药物警戒的核心环节，及时准确地识别潜在的药品不良反应信号对于保障患者用药安全至关重要。基于电子健康档案（EHR）的真实世界数据为药物安全信号检测提供了丰富的资源，但如何在真实世界数据中实现高灵敏度和高特异性的信号检测仍是一个方法学挑战。自体对照病例序列（SCCS）设计因其可控制个体间混杂因素而备受关注，而引入活性对照可能进一步控制适应证导致的混杂偏倚。本研究以英国临床实践研究数据库（CPRD Aurum）为数据源，系统评价了SCCS设计在有无活性对照条件下的信号检测性能，为基于电子健康档案的药物警戒方法学发展提供了重要证据。 核心发现 • 构建了包含104个阳性对照和58个阴性对照的参考标准集，确保药物-结局配对在理论上适合SCCS设计 • 无活性对照的SCCS灵敏度为0.57、特异度为0.77；加入活性对照后特异度提高至0.89，但灵敏度下降至0.18 • 5个药物-结局配对在出现在药品标签之前即被SCCS方法识别为不平衡信号 • 使用大环内酯类和氟喹诺酮类抗生素作为目标药物，阿莫西林和头孢氨苄作为活性对照，覆盖全部器官类别的30个结局 领域意义 本研究对医院药物警戒工作具有直接的方法学指导价值。SCCS设计在CPRD数据库中展现出中等水平的信号检测性能，为医院药物不良反应监测提供了可借鉴的分析框架。研究表明活性对照可有效减少适应证混淆，但可能因统计效力下降而降低阳性信号的检出能力，这为医院药学科在真实世界药物安全研究中平衡特异度和灵敏度提供了重要参考。该方法学框架可应用于医院电子病历系统的药物不良反应主动监测中，帮助临床药师更精确地识别潜在药物安全问题。 英文摘要 (Abstract) Background: There is little evidence about signal detection using UK primary care electronic health records (EHRs). The self controlled case series (SCCS) is one of the most promising methods for drug safety signal detection using real world data, and incorporating active comparators could potentially improve its performance by addressing confounding by indication. Objectives: This study aims to evaluate the performance of the SCCS with and without active comparators for signal detection using the UK Clinical Practice Research Datalink (CPRD) Aurum. Methods: We applied the SCCS to macrolide and fluoroquinolone antibiotics, using amoxicillin and cefalexin as active comparators. In total seven drugs, and 30 outcomes from all organ classes were selected. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. Two-year observation periods with a 30-day risk window after each dispensing were used. Diagnostic performance was measured using sensitivity and specificity with respect to the product labels. Results: The sensitivity and specificity of the SCCS without active comparator in the 2017/2018 observation period were 0.57 and 0.77 when limited to pairs with satisfactory power. Specificity increased up to 0.89 with active comparators, however sensitivity decreased to 0.18. Five drug-outcome pairs were signals of disproportionality before they were present on labels. Conclusions: Using a carefully designed reference set of drug-outcome pairs well suited to the study design, the SCCS performed moderately well for signal detection in CPRD. Whilst active comparators effectively reduced confounding by indication, they also reduced the number of correctly identified positive controls, due to a reduction in power. We showed some evidence that SCCS is able to highlight SDRs before they were present on labels. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎Original Research Predictors of Direct Oral Anticoagulant Use in Northern Italy: A Population-Based Study Pharmacoepidemiol Drug Saf 丨 2025-12-XX 丨 Original Research ▍北意大利直接口服抗凝药使用的预测因素：一项基于人群的研究 研究背景 直接口服抗凝药（DOACs）已成为房颤和静脉血栓栓塞症抗凝治疗的主流选择。然而，不同DOACs（阿哌沙班、利伐沙班、达比加群、艾多沙班）之间的头对头比较证据有限，临床实践中DOAC选择和转换的驱动因素尚不明确。临床指南通常不会明确推荐某一种DOAC优于其他DOAC，但在真实世界的处方实践中可能存在特定的处方模式。了解影响临床决策的因素对于优化抗凝治疗管理、促进合理用药和识别潜在的不当处方模式具有重要意义。本研究利用意大利伦巴第大区的卫生行政数据库，分析了2019-2022年间近16万例新起始DOAC使用者的处方模式、预测因素和转换情况。 核心发现 • 共识别159,993名DOAC新使用者，阿哌沙班使用比例从29.0%上升至34.3%，而达比加群从20.7%下降至11.5% • 高龄和女性性别是艾多沙班处方的预测因素；合并症主要与阿哌沙班使用相关；缺血性心脏病或心梗病史者优先使用达比加群 • DOAC总体转换率为5.6%，阿哌沙班是最常被选择的第二种DOAC；达比加群主要在有血管缺血性事件后被选为第二种DOAC • 有出血史的患者优先被处方阿哌沙班和艾多沙班，外周动脉疾病患者倾向于使用利伐沙班 领域意义 本研究为医院药学中抗凝药物管理提供了重要的真实世界证据。了解不同DOAC的处方预测因素有助于医院药师在抗凝治疗方案的制定和评估中发挥更积极的作用。研究发现阿哌沙班的处方偏好呈上升趋势，而达比加群使用量下降，这反映了真实临床实践中对抗凝药物的风险-获益评估趋势。出血史患者优先使用阿哌沙班和艾多沙班的模式提示临床医生对特定DOAC安全性的认知在影响处方决策。这些数据有助于医院药学部门制定基于证据的抗凝药物管理策略，优化个体化抗凝治疗方案，并为医院药事管理中抗凝药物的处方审核和药学监护提供参考。 英文摘要 (Abstract) Purpose: Evidence on head-to-head comparison between direct oral anticoagulants (DOACs) is lacking, and the reasons for choosing one type of DOAC and switching from one DOAC to another are scarce. This study investigated the use of DOACs in an unselected population in Northern Italy during a recent period. Methods: Using the health administrative database of the Lombardy region, subjects aged 45 years and older who started DOAC therapy between 2019 and 2022 were included in the analysis. Logistic regression analysis was used to evaluate predictors associated with DOAC prescription, and results were presented as ORs with 95% CI. DOAC switching was assessed by estimating the prevalence and cumulative incidence according to the first prescribed DOAC. Results: Overall, 159 993 new users for DOAC were identified. Apixaban users increased from 29.0% to 34.3%, whereas dabigatran users decreased from 20.7% to 11.5% over time. Across all pair-wise comparisons, older age and female sex were predictors for edoxaban prescription. Comorbidities were mainly associated with the use of apixaban; however, dabigatran was preferred in patients with a history of ischemic heart disease or myocardial infarction and rivaroxaban in those with peripheral artery disease. Both apixaban and edoxaban were preferentially prescribed to patients with a history of bleeding. The switching rate of DOACs was 5.6% with apixaban as the most preferred drug as a second choice. Dabigatran was mainly chosen as a second DOAC after a vascular ischaemic event. Conclusion: Given the lack of evidence on factors influencing clinician behavior in the use of DOACs, our findings provide insight into this topic in a real-world setting. As the use of these agents increases, further evidence is needed to better explore this issue. Our data could contribute to the development of recommendations in clinical practice. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎Original Research Measuring Exposure to Opioids Using Self-Reported Medication Use Data Versus General Practitioner Prescription Records in the UK Biobank Study Pharmacoepidemiol Drug Saf 丨 2025-12-XX 丨 Original Research ▍英国生物银行研究中自我报告用药数据与全科医师处方记录在阿片类药物暴露测量中的比较 研究背景 全球范围内阿片类药物的使用持续增长，使得研究其长期健康影响的重要性日益凸显。前瞻性队列研究通常依赖自我报告的用药数据，但这类数据可能因回忆偏倚、社会期望偏倚和药物识别能力有限等因素而存在偏差。相比之下，处方记录被视为更客观的用药暴露测量指标，但也可能遗漏非处方来源和未记录的实际使用情况。两种数据来源的一致性和差异对于药物流行病学研究的方法学质量具有重要影响。本研究利用英国生物银行（UK Biobank）大规模队列中171,813名参与者的数据，系统比较了自我报告规律用药与全科医师（GP）处方记录在阿片类药物暴露测量中的一致性。 核心发现 • 自我报告规律阿片类药物使用与处方记录之间一致性为中等至实质性，过去365天内≥3张处方的一致性最佳（Cohen's Kappa = 0.66） • 镇痛类阿片类药物一致性（Kappa = 0.43-0.63）显著优于非镇痛类阿片类药物（Kappa = 0.25-0.34） • 距末次处方记录时间越长，遗漏报告（omission）的概率越高；慢性疼痛患者遗漏率最低但错误报告率（commission）最高 • 自我报告可捕获来自未关联来源的阿片类药物使用情况，对于镇痛类阿片是一个有效的暴露评估指标 领域意义 本研究对医院药学中的药物利用研究和阿片类药物安全管理具有重要的方法学参考价值。研究结果提示，在进行药物流行病学研究中，自我报告数据和处方记录各有优劣，应根据研究目的和药物类别选择合适的暴露测量指标。对于医院药学部门开展的阿片类药物利用评价和风险管理，本研究的发现有助于理解不同数据来源可能导致的偏倚。在评估住院患者的院外用药史时，医院药师应注意仅依赖处方记录可能低估镇痛类药物的实际使用情况，而需要综合多种信息源进行全面评估。该研究也为医院建立阿片类药物监测体系提供了方法学依据。 英文摘要 (Abstract) Purpose: The ongoing global increase in opioid use necessitates studies examining long-term health impacts. Prospective cohorts frequently rely on self-reported medication use data which may be subject to several types of bias compared to more objective measurements. We evaluated the agreement between two opioid exposure measures in the UK Biobank (UKBB)-self-reported regular use and prescription-based indicators using linked general practitioner (GP) records. Methods: Our analysis included 171 813 UKBB participants with linked prescription records. At baseline, participants reported medications taken regularly (weekly, monthly, every 3 months). We assessed agreement between self-reported regular opioid use and opioid prescription records prior to enrollment across various look-back periods and prescription counts. Logistic regressions assessed factors associated with omission and commission. Results: Agreement was moderate to substantial between self-reported opioid use and prescription records. The strongest agreement was observed for ≥ 3 prescriptions in the past 365 days (Cohen's Kappa = 0.66). Subgroup analysis showed better agreement for analgesic opioids (Kappa = 0.43-0.63) than for non-analgesic opioids (Kappa = 0.25-0.34). Omission odds were highest with increasing months since the last record and lowest for individuals with chronic pain. Commission odds were highest for individuals with chronic pain and lowest in married/partnered individuals. Conclusions: This analysis indicates that self-reported regular opioid use in the UKBB could be a valid indicator for identifying individuals with repeated prescriptions for analgesic opioids in the past year, while also capturing opioid use from non-linked sources. However, agreement was low for non-analgesic opioids, suggesting limited utility of self-report for capturing use of these medications. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎Systematic Review Efficacy and Safety of All Monoclonal Antibodies in Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis Pharmacoepidemiol Drug Saf 丨 2025-12-XX 丨 Systematic Review ▍单克隆抗体治疗中重度特应性皮炎的疗效与安全性：系统综述与网络荟萃分析 研究背景 特应性皮炎（AD）是一种慢性、复发性炎症性皮肤病，严重影响患者生活质量。近年来，针对AD免疫病理机制的单克隆抗体（mAb）治疗迅速发展，多种新型生物制剂相继获批上市或在临床试验中展现出良好的治疗效果。然而，不同单克隆抗体之间的疗效和安全性缺乏直接的头对头比较研究，临床决策面临如何选择最优治疗方案的挑战。网络荟萃分析（NMA）作为可同时比较多种干预措施的统计学方法，为综合评估各单克隆抗体在AD治疗中的相对疗效和安全性提供了重要工具。本研究对截至2024年11月的所有相关随机对照试验进行了系统检索和网络荟萃分析。 核心发现 • 纳入32项RCT共7,588例患者，全面比较了多种单克隆抗体在中重度AD中的疗效和安全性 • Spesolimab、Rademikibart、Dupilumab和Amlitelimab在EASI-50、EASI-75、EASI-90和IGA改善方面均显著优于安慰剂 • 根据SUCRA排序，Dupilumab在瘙痒NRS评分、EASI评分和SCORAD评分的百分比变化方面表现出相对较好的疗效 • Dupilumab的严重不良事件发生率显著低于安慰剂（RR = 0.43, 95% CI 0.30-0.63），其他安全性分析结果无统计学差异 领域意义 本系统综述对医院药学中生物制剂的管理和使用具有重要的临床指导价值。研究通过网状荟萃分析综合比较了多种单克隆抗体在AD中的相对疗效和安全性，为临床药师的药物选择和治疗方案制定提供了循证依据。Dupilumab在疗效综合排名和安全性方面表现突出，特别是其严重不良事件发生率显著低于安慰剂的发现，进一步支持了其在AD治疗中的优选地位。随着生物制剂的广泛使用，医院药学科在生物制剂的处方审核、药学监护和用药教育中需要基于最新的证据，本研究提供的比较疗效和安全性数据可作为重要的决策参考。 英文摘要 (Abstract) Objective: The aim of this study was to compare the efficacy and safety of monoclonal antibodies (mAb) for moderate-to-severe atopic dermatitis (AD). Methods: The randomized controlled trials (RCTs) of monoclonal antibodies in the treatment of moderate-to-severe AD were searched in the database of PubMed, Embase, Web of Science and Cochrane Library, up to November 2024. The control group included placebo. The efficacy indicators were the percentage of patients achieving 50%, 75%, 90% improvement in Eczema Area and Severity Index score (EASI-50, EASI-75, EASI-90) and the percentage of patients with an Investigator Global Assessment (IGA) Score of 0 or 1 from baseline until the time of efficacy observation, and the percent change in Pruritus Numerical Rating Scale (NRS), EASI score, SCORing Atopic Dermatitis (SCORAD), and change in Percent Body Surface Area (BSA), Dermatology Life Quality Index (DLQI). The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95% CI) were used as effect sizes to analyze binary categorical variables. Results: This study included 32 RCTs with 7588 patients. Spesolimab, Rademikibart, Dupilumab, Amlitelimab were more effective than placebo in EASI-50 (RRs ranging between 1.31 and 22.65), EASI-75(RRs ranging between 1.51 and 36.58), EASI-90(RRs ranging between 3.72 and 5.49), and the percentage of patients in IGA score of 0 or 1 (RRs ranging between 1.78 and 13.36). Dupilumab showed relatively good efficacy according to SUCRA ranking on percent change in NRS, EASI, SCORAD. Dupilumab exhibited a lower incidence of serious adverse events than placebo, and the difference was statistically significant (RR = 0.43, 95% CI 0.30-0.63). Other safety analysis results showed no statistical difference. Conclusions: Through the analysis of the primary efficacy indicators, this network meta-analysis (NMA) study indicated that all monoclonal antibodies performed better than placebo. Based on the results of this study, Spesolimab, Rademikibart, Dupilumab, Amlitelimab were recommended treatment options with relatively good efficacy and safety. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ▎参考文献·References [1] High-Throughput Screening Using the Self-Controlled Tree-Based Scan Statistic to Identify Medications Associated With Hospitalization for Severe Acute Liver Injury. Pharmacoepidemiol Drug Saf. 2025-12-XX. doi: 10.1002/pds.70275. https://doi.org/10.1002/pds.70275 [2] Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using the Clinical Practice Research Datalink (CPRD). Pharmacoepidemiol Drug Saf. 2025-12-XX. doi: 10.1002/pds.70243. https://doi.org/10.1002/pds.70243 [3] Predictors of Direct Oral Anticoagulant Use in Northern Italy: A Population-Based Study. Pharmacoepidemiol Drug Saf. 2025-12-XX. doi: 10.1002/pds.70300. https://doi.org/10.1002/pds.70300 [4] Measuring Exposure to Opioids Using Self-Reported Medication Use Data Versus General Practitioner Prescription Records in the UK Biobank Study. Pharmacoepidemiol Drug Saf. 2025-12-XX. doi: 10.1002/pds.70280. https://doi.org/10.1002/pds.70280 [5] Efficacy and Safety of All Monoclonal Antibodies in Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis. Pharmacoepidemiol Drug Saf. 2025-12-XX. doi: 10.1002/pds.70268. https://doi.org/10.1002/pds.70268 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ 医院药学研究导读丨聚焦全球医院药学前沿动态 关注我们，追踪全球药学前沿 第5期 丨 总第25期 丨 2026年6月

2026年上半年的中国新药审批节奏明显加快。根据NMPA公开信息统计，上半年获批上市的新药超过30个，适应症横跨实体瘤、血液肿瘤、自身免疫性疾病与罕见病等多个治疗领域。 进入下半年，一批在审评管线中蓄势已久的重磅品种即将陆续落地。本文梳理了当前处于或优先审评阶段、或关键临床数据已有公开披露的8款药物，有望为相关适应症带来实质性的治疗格局改变。 替恩戈替尼（药捷安康） 替恩戈替尼是一款多靶点小分子激酶抑制剂，区别于第一代选择性FGFR抑制剂，其机制覆盖了FGFR通路及肿瘤微环境调控，在已对FGFR抑制剂产生耐药的群体中展现出持续的临床活性。该药已获美国FDA胆管癌孤儿药认定、快速通道资格，欧洲EMA孤儿药认定，以及NMPA优先审评与突破性治疗品种认定。 2026年ASCO大会上，药捷安康公布了替恩戈替尼关键II期数据，入组的50例晚期胆管癌患者均接受过至少一线化疗及FGFR抑制剂治疗，66%曾使用免疫治疗，40%经历≥3线系统性治疗。中位随访12个月，核心疗效指标如下：客观缓解率：28.0%（14例确认部分缓解），疾病控制率：82.0%，中位总生存期：20.7个月，18个月生存率 51.8%。上述数据建立在FGFR抑制剂经治这一高度难治人群中。20.7个月的中位OS在这一基线水平下具有明确的临床意义。 目前替恩戈替尼的NDA已获NMPA受理，若顺利获批，它将成为全球首个申报上市的、专门针对FGFR抑制剂经治复发/难治胆管癌的在研药物。该品种同时在海外推进国际多中心III期注册研究。 他舒替尼| 赛生药业 / 卫材 他舒替尼是卫材开发的一款成纤维细胞生长因子受体选择性酪氨酸激酶抑制剂，对FGFR1、FGFR2和FGFR3均表现出选择性抑制活性。2024年9月，该药率先在日本获批，适应症为携带FGFR2基因融合或重排、化疗后进展的不可切除胆道癌。全球目前仅3款FGFR抑制剂获批用于胆道癌——Incyte的Pemigatinib、大鹏药品的Futibatinib，以及卫材的他舒替尼。 在日本获批所依据的多中心、开放标签、单臂II期注册研究中，他舒替尼在经化疗后进展的胆管癌人群中取得的30%客观缓解率与5.4个月中位PFS，与已获批的同类FGFR抑制剂处于同一疗效区间。若在中国顺利获批，他舒替尼将成为国内FGFR2融合胆管癌治疗的第一款标准靶向药物，率先打破这一人群无药可用的局面。 而对于下半年同赛道冲刺的替恩戈替尼和凡瑞格拉替尼而言——两药均定位在FGFR抑制剂经治后人群——他舒替尼的获批将构成前序治疗选择，三者有望在胆管癌FGFR通路的"前线→后线"序列治疗中形成衔接。 凡瑞格拉替尼| 和黄医药 和黄医药自主研发的高选择性FGFR1/2/3抑制剂凡瑞格拉替尼，同样是2026年FGFR赛道不可忽视的选手。其NDA于2025年12月获NMPA受理并纳入优先审评，关键II期注册数据将在7月4日慕尼黑ESMO GI大会上做口头报告——这一待遇本身就传递了学界对其数据质量的认可。 该研究覆盖国内53家中心，入组患者全部经过化疗，72%曾使用免疫治疗，高度贴近中国胆管癌后线治疗的真实场景。核心数据梳理如下：客观缓解率：42.5%，疾病控制率：83.9%， 中位无进展生存期：6.9个月， 中位总生存期：16.6个月。安全性方面，≥3级药物相关不良事件发生率48.3%，以肝酶升高和掌跖红肿综合征为主，因不良反应停药率仅2.2%，未发生治疗相关死亡——整体风险谱与选择性FGFR抑制剂一致，无明显超预期信号。42.5%的ORR在同类经治人群中属于亮眼水平，1.4个月的快速起效对后线患者尤其具有现实意义。 OAV101| 诺华 脊髓性肌萎缩症由SMN1基因双等位缺失或变异导致，诺华的onasemnogene abeparvovec是全球首个获批的SMA基因替代疗法，通过AAV载体将功能性SMN1基因一次性递送至体内，目前已在美国、欧盟、日本上市。 2025年8月，OAV101静脉注射剂型的中国上市申请获NMPA受理，用于6月龄及以上5q型SMA患者。III期STEER试验纳入2–18岁非坐立SMA患者，接受单次鞘内注射后，治疗组在哈默史密斯运动量表上获得具有统计学意义的改善。鞘内给药的精准局部递送方式有效规避了静脉给药中令人担忧的急性肝损伤风险，这为基因治疗向全年龄段拓展提供了关键的安全性背书。可以预见，OAV101若在中国获批，将进一步重塑国内SMA治疗格局：从"终身管理"走向"一次干预"，从"婴幼儿专属"走向"跨年龄段可及"。 瑞西奇拜单抗 | 华海药业 IL-36R是泛发性脓疱型银屑病（GPP）的核心致病通路靶点。目前全球仅有勃林格殷格翰的司柏索利单抗获批该适应症，中国市场在IL-36R靶向上仍由进口产品独占。华海药业子公司华奥泰自主研发的瑞西奇拜单抗（HB0034）正是瞄准了这一缺口。 2025年10月，该药的GPP适应症上市申请获CDE受理并纳入优先审评。关键性临床研究中，瑞西奇拜单抗单次静脉注射后第一周，患者皮肤脓疱即出现明显清除，达到预设主要终点。安全性评估未发现新的风险信号。国内目前有6款IL-36R抗体进入临床，但瑞西奇拜单抗在注册进度上领先一个身位。 柯美奇拜单抗 | 麦济生物  IL-4Rα赛道无疑是2026年竞争最激烈的自免靶点之一。目前市面上主流抗IL-4Rα单抗的给药方案均为每2周一次。麦济生物的柯美奇拜单抗通过Fc突变技术将半衰期延长至32天，首次注射后4周即达稳态血药浓度并维持有效水平，实现了每4周一次的给药方案——在同类中属于全球首创。 2026年6月中华医学会皮肤病学术年会上，北京大学人民医院赵琰教授以口头报告发布了柯美奇拜单抗III期52周长期数据，300mg Q4W给药方案下：EASI-75 达标率（52周）：94.3%；EASI-90 达标率（52周）：79.1%；IGA 0/1 达标率（52周）：76.6%； PP-NRS 瘙痒改善≥3分比例：84.6%；DLQI 生活质量改善≥4分比例：81.9%。 安全性方面，结膜炎发生率双盲期仅3.0%，维持期2.4%，注射部位反应≤1.8%，未发生特别关注不良事件或死亡。在疗效数值不输进口产品的前提下，将注射频率砍半，对特应性皮炎这类需要长期管理的慢性疾病而言，依从性优势本身就是一张硬牌。 乐德奇拜单抗 | 先声药业  先声药业引进的乐德奇拜单抗于4月29日提交NDA并获受理，目标适应症为成人及青少年特应性皮炎。先声以1.5亿元首付款+最高8.75亿元里程碑、外加两位数销售分成的代价拿下大中华区权益。该品种的一大特征是"越用越深"：第16周EASI-75/90和IGA 0/1应答率分别为74.2%、43.0%和47.7%，已显示出较好的早期获益；至第52周，三个指标分别攀升至96.6%、85.3%和87.1%，提示持续治疗下深度缓解优势持续累积。在同靶点竞品中，这一"爬坡式改善"的轨迹是一个值得关注的差异化信号。 偌考奇拜单抗 | 君实生物  君实生物的偌考奇拜单抗是一款基于自主专利CDR序列开发的差异化IL-17A抑制剂，申报适应症为中重度斑块状银屑病。2026年EULAR大会上，君实还首次披露了其在强直性脊柱炎中的II期数据，显示该品种正在向银屑病关节炎/脊柱关节炎方向拓展。 AS II期临床中，第16周JS005 150mg组和300mg组的ASAS 40达标率分别为51.4%和46.4%，显著高于安慰剂组的25.6%。ASDAS-CRP等次要终点同样支持治疗获益，且不良事件发生率与安慰剂基本相当。银屑病适应症的NDA已获NMPA受理，150mg预充式注射器与自动注射器两种规格同步申报。对上半年刚获批的古莫奇单抗而言，偌考奇拜单抗的入场将直接改变IL-17市场的竞争密度。 数据来源：本文基于NMPA、CDE、国际学术会议摘要整理。 精彩回顾： 肺纤维化创新药历史性突破：勃林格全球首创PDE4B选择性抑制剂将中位生存期从3.7年提升到9.1年，让患者看见退休后的夕阳 一日拿下两项“全球首证”，中国创新药闯入全球“无人区” 平均甩掉63斤！礼来三重激动剂逼平减重手术，人类终于按下代谢疾病"重置键" 药企“抄底”自己，医药股的机会来了？ 点击关注新康界，获取更多热点分析/行研报告/蓝皮书。 【免责声明】 1.“新康界”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。 2.“新康界”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。 3.“新康界”所有信息仅供参考，不做任何商业交易及或医疗服务的根据，如自行使用“新康界”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。 4.本声明未涉及的问题参见国家有关法律法规，当本声明与国家法律法规冲突时，以国家法律法规为准。