• As specialty products, therapies for Crohn’s disease (CD) can be expensive, and formulary positioning is paramount to product uptake. Payers are settled in vital contracts that lead them to prioritize broad immunology drugs, Humira and Remicade. This has posed a high barrier for newer entrants to the market, which cannot compete in volume and rebates. Biosimilar and generic competition will further undermine the likely premium pricing of newer drugs and pipeline products.
  作为专科治疗药物，克罗恩病(CD)疗法价格昂贵，医保目录准入对产品市场渗透至关重要。支付方已签订关键合约，使其优先考虑广谱免疫药物修美乐和类克。这为市场新进入者设置了高门槛，后者难以在销量和返利方面竞争。生物类似药和仿制药的竞争将进一步削弱新药及在研产品可能采取的高溢价策略。

• Over the next decade, all key marketed brands for CD will face patent expiry. Thus far, the European market has taken the brunt of biosimilar erosion, with earlier launches and more acceptance compared to other countries. In the US, biosimilars will face challenges in usurping branded anti-TNFs, with adalimumab biosimilars launched in 2023, substantial originator rebates, and exclusive contracting with payers. Over time, biosimilar penetration is anticipated to gain more momentum as international real-world evidence accumulates and long-term data support biosimilar efficacy and safety. This should allow physicians and patients to grow their confidence and familiarity with biosimilars and encourage uptake.
  未来十年内，所有已上市的关键克罗恩病治疗品牌药都将面临专利到期。截至目前，欧洲市场承受了生物类似药冲击的主要压力，与其他国家相比，其生物类似药上市更早且接受度更高。在美国市场，生物类似药要取代品牌抗 TNF 药物仍面临挑战——阿达木单抗生物类似药于 2023 年上市，但原研药提供大幅折扣并与支付方签订独家合约。随着国际真实世界证据的积累以及长期数据对生物类似药疗效和安全性的支持，预计生物类似药的市场渗透将逐步加速。这将有助于增强医患群体对生物类似药的信心与熟悉度，从而促进其使用。

• Stelara biosimilars first hit the US market in January 2025, following licensing deals and patent expiry in 2024. Five biosimilars have launched in the US with more expected to launch in the first half of 2025. In the final three months of 2024, Stelara sales dropped by 14.7% to $2.35bn, with international sales plummeting by almost a third – down 32.7% at $650m – in the face of European biosimilar competition.
  乌司奴单抗生物类似药于 2024 年专利到期后，通过许可协议于 2025 年 1 月首次登陆美国市场。目前美国已有五款生物类似药上市，预计 2025 年上半年还将有更多产品面世。面对欧洲生物类似药的竞争，2024 年最后三个月乌司奴单抗销售额下降 14.7%至 23.5 亿美元，其国际销售额暴跌近三分之一——降幅达 32.7%，仅剩 6.5 亿美元。

• Nevertheless, the CD market is projected to expand, propelled by a growing patient caseload and the introduction of pipeline products. Datamonitor Healthcare estimates that in 2024, there were 1.64 million diagnosed prevalent cases of CD in the US, Japan, and five major European markets. By 2043, we forecast that the number of diagnosed prevalent cases of CD will decrease slightly to 1.62 million.
  然而，在患者数量增长和管线产品推出的推动下，克罗恩病（CD）市场预计将持续扩张。Datamonitor Healthcare 数据显示，2024 年美国、日本及欧洲五大主要市场的 CD 确诊患病病例达 164 万例。我们预测到 2043 年，CD 确诊患病病例数将小幅下降至 162 万例。

• AbbVie’s Skyrizi is the first IL-23 inhibitor targeting the p19 subunit for CD. This selective inhibition gives the drug a slight edge, with better remission rates and a faster onset of efficacy in cross-trial comparisons with other interleukin inhibitors. Topline results from the open-label Phase III SEQUENCE trial showcased Skyrizi’s superior results over Stelara, increasing expectations of selective IL-23 inhibitors. Another such product, Omvoh (mirikizumab), demonstrated non-inferiority against Stelara but failed to achieve superiority on endoscopic response even with a numerically higher result in its Phase III VIVID-1 trial.
  艾伯维的 Skyrizi 是首个靶向 p19 亚基的 IL-23 抑制剂。这种选择性抑制使该药物在与其他白细胞介素抑制剂的跨试验比较中略具优势，展现出更好的缓解率和更快的起效速度。开放标签 III 期 SEQUENCE 试验的顶线结果证实，Skyrizi 疗效优于 Stelara，这提升了对选择性 IL-23 抑制剂的期待。同类产品 Omvoh（mirikizumab）在 III 期 VIVID-1 试验中虽数值表现更优，但仅证明对 Stelara 的非劣效性，未能达到内镜反应方面的优效性。

• Johnson & Johnson released top-line results from the GALAXI 2 and 3 Phase III trials earlier in 2024. Both subcutaneous doses of 200mg every four weeks and 100mg every eight weeks showed superiority versus both placebo and ustekinumab, sparking anticipation for Tremfya's potential impact on the market. Tremfya, which is already launched for plaque psoriasis, recently gained approval for ulcerative colitis (UC) and is positioned to become the fourth-to-market drug in its class to treat CD. Johnson & Johnson has extensive experience in the inflammatory bowel disease (IBD) field through Stelara and will be confident in its strategy to promote Tremfya.
  强生公司于 2024 年初公布了 GALAXI 2 和 3 两项 III 期临床试验的顶线结果。无论是每四周 200 毫克还是每八周 100 毫克的皮下注射剂量，均显示出优于安慰剂和乌司奴单抗的疗效，这引发了市场对特诺雅潜在影响力的期待。已获批用于斑块状银屑病的特诺雅，近期又获得溃疡性结肠炎（UC）适应症批准，有望成为该类药物中第四个进入克罗恩病（CD）治疗市场的产品。凭借斯泰拉在炎症性肠病（IBD）领域的丰富经验，强生对特诺雅的推广策略充满信心。

• Bristol Myers Squibb's entry into the CD market has hit a major setback as its only pipeline candidate in the indication, Zeposia, failed to achieve the primary endpoint at week 12 in the initial analysis of the first of two induction studies in the Phase III YELLOWSTONE trial.
  百时美施贵宝进军 CD 市场的计划遭遇重大挫折，其在该适应症中唯一的管线候选药物 Zeposia，在 III 期黄石试验两项诱导研究的第一项初步分析中，未能达到第 12 周的主要终点。

• Eli Lilly's Omvoh is the latest addition to the CD treatment armamentarium having gained FDA approval in January 2025. The company noted that Omvoh has gained first-line biologic coverage from two of the three largest pharmacy benefit managers in the US. This could provide a much-needed boost for Omvoh in directly challenging Skyrizi (which already has favorable formulary positioning) as both the products will be placed in the preferred specialty tier and does not require failure of other biologics prior to use.
  礼来公司的 Omvoh 成为克罗恩病治疗领域的最新成员，已于 2025 年 1 月获得食品药品监督管理局批准。该公司指出，Omvoh 已获得美国三大药房福利管理机构中两家的首选生物制剂覆盖资格。这将为 Omvoh 直接挑战 Skyrizi（该药物已具备有利的医保目录地位）提供亟需的助力——两种药物都将被列入优先专科用药层级，且无需患者先对其他生物制剂治疗失败即可使用。

• In May 2023, AbbVie’s Rinvoq gained approval as the first JAK inhibitor and first oral drug in CD. Although the drug comes with a black box warning, the convenience of an oral formulation and positive topline results from both induction and maintenance trials fortify its market position.
  2023 年 5 月，艾伯维的 Rinvoq 作为首个 JAK 抑制剂和首个克罗恩病口服药物获得批准。尽管该药物带有黑框警告，但口服剂型的便利性以及诱导期和维持期试验的积极主要结果巩固了其市场地位。

• Although the JAK inhibitors are plagued by black box warnings, physicians in the gastrointestinal community have opined that the adverse events seen are much more pronounced in the rheumatoid arthritis (RA) population. On the other hand, the IBD patient population is younger and less prone to cardiovascular events, and this has improved physician confidence in prescribing JAK inhibitors in CD.
  尽管 JAK 抑制剂受到黑框警告的困扰，但消化内科医生认为这些不良反应在类风湿关节炎（RA）患者群体中更为显著。另一方面，炎症性肠病（IBD）患者群体更年轻且心血管事件发生率更低，这增强了内科医生在克罗恩病（CD）中开具 JAK 抑制剂处方的信心。

• AstraZeneca has discontinued development of brazikumab, owing to the estimated development timeline and the evolving competitive landscape. Meanwhile, Jyseleca, a pipeline agent that was touted as a potential competitor to Rinvoq, will not be filed for approval with the European Medicines Agency (EMA) due to disappointing results in the pivotal Phase III DIVERSITY trial, and is also no longer in development in the US.
  由于预估开发周期延长及竞争格局变化，阿斯利康已终止 brazikumab 的研发。与此同时，曾被吹捧为 Rinvoq 潜在竞争者的在研药物 Jyseleca，由于在关键 III 期 DIVERSITY 试验中结果令人失望，将不再向欧洲药品管理局（EMA）提交上市申请，同时在美国的开发计划也已终止。

• In October 2023, Takeda released disappointing data from the Phase III ADMIRE-CD-II trial in the US for Alofisel, where the stem cell therapy did not achieve the primary endpoint of combined remission at week 24. The drug is no longer in development in the US and following a review from EMA’s committee for advanced therapies, the company has also withdrawn from the European market. 
  2023 年 10 月，武田制药在美国公布了 Alofisel 干细胞疗法三期 ADMIRE-CD-II 试验的令人失望的数据，该疗法未能达到第 24 周联合缓解的主要终点。该药物已终止在美国的开发，经欧洲药品管理局先进疗法委员会审查后，公司也已从欧洲市场撤出。

• Significant unmet needs include targeting inadequate responders to biologic and conventional therapies, as well as underserved patients with fistulas. In terms of clinical trials, active comparators and endoscopic endpoints should be prioritized as there is a stark absence of head-to-head data and the field is moving towards endoscopic treatment goals. Additionally, new mechanisms of action and convenient oral therapies that are safe and effective are desirable. Pricing will be critical to secure favorable positioning in formularies and maximize commercial opportunities.
  显著未满足的医疗需求包括：针对生物制剂和传统疗法反应不足的患者群体，以及瘘管病症未获充分治疗的患者。在临床试验方面，应优先采用活性药物对照和内镜评估终点——目前领域内极度缺乏头对头比较数据，且治疗目标正转向内镜下愈合。此外，需要开发安全有效的新作用机制口服疗法以提升用药便利性。定价策略对确保进入医保目录和最大化商业机会至关重要。

Definition  定义

Crohn's disease (CD) is a form of chronic IBD that causes transmural inflammation in the digestive tract. The disease course is characterized by periods of remission sporadically interspersed with inflammatory flares.
克罗恩病(CD)是一种慢性炎症性肠病，可引发消化道透壁性炎症。该疾病病程特征为缓解期与炎症发作期交替出现。

Symptoms  症状

The disease is highly heterogeneous; it may affect any part of the digestive tract from the mouth to the anus. There are no fundamental pathognomonic features. Typical symptoms include:
该疾病具有高度异质性；可能影响从口腔到肛门的消化道任何部位。不存在根本性的特异性病理特征。典型症状包括：

• diarrhea  腹泻

• abdominal pain  腹痛

• rectal bleeding  直肠出血

• fever  发热

• anemia  贫血

• weight loss  体重减轻

• fatigue.  疲劳

CD is progressive and destructive. Due to intestinal complications, as many as 50% of patients undergo intestinal resection within a decade of diagnosis. Downstream complications include:
克罗恩病具有进行性和破坏性。由于肠道并发症，多达 50%的患者在确诊后十年内需接受肠道切除术。后续并发症包括：

• intestinal obstruction  肠梗阻

• fistulas  瘘管

• abscesses  脓肿

• ulcers  溃疡

• anal fissures  肛裂

• malnutrition.  营养不良

Approximately 21% to 47% of patients present with extraintestinal manifestations (EIMs). These have negative long-term consequences impacting quality of life, and increase the risk of hospitalization and surgery. EIMs may affect multiple systems:
约 21%至 47%的患者会出现肠外表现（EIMs）。这些症状会对生活质量产生长期负面影响，并增加住院和手术风险。肠外表现可能累及多个系统：

• ocular (uveitis, scleritis)
  眼部疾病（葡萄膜炎、巩膜炎）

• hepatobiliary disease (primary sclerosing cholangitis)
  肝胆疾病（原发性硬化性胆管炎）

• arthropathy (axial and peripheral)
  关节病变（中轴和周围关节）

• dermatological (erythema nodosum)
  皮肤病（结节性红斑）

• metabolic bone diseases.
  代谢性骨骼疾病

Patient segmentation  患者分型

There is no standard definition of disease severity in treatment guidelines available for CD. Patients’ disease severity may range from remission to mild, moderate, and severe/fulminant CD. Perianal fistulizing CD occurs in up to one in four patients.
目前克罗恩病的治疗指南中尚无对疾病严重程度的统一定义。患者的病情严重程度可能从缓解期到轻度、中度乃至重度/暴发性克罗恩病不等。约四分之一的患者会出现肛周瘘管型克罗恩病。

The treatment armamentarium for CD comprises traditional 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, antibiotics, and immunomodulators. More recently, treatment options have expanded to include biologics, such as the anti-TNFs, leukocyte trafficking-targeting Entyvio (vedolizumab) and Tysabri (natalizumab), and anti-interleukin-12/23 (IL-12/23) antibody Stelara (ustekinumab). In June 2022, Skyrizi (risankizumab) was approved in the US as the first IL-23 inhibitor targeting the p19 subunit for CD. In May 2023, Rinvoq (upadacitinib) was approved in the US; however, the drug has been relegated to later lines of therapy to patients who cannot tolerate one or more TNF blockers, which has eliminated the ability for JAK inhibitors to be used in the first-line setting.
克罗恩病的治疗手段包括传统 5-氨基水杨酸（5-ASA）制剂、皮质类固醇、抗生素和免疫调节剂。近年来，治疗方案已扩展至生物制剂，如抗肿瘤坏死因子药物、靶向白细胞迁移的 Entyvio（维多珠单抗）和 Tysabri（那他珠单抗），以及抗白细胞介素-12/23（IL-12/23）抗体 Stelara（乌司奴单抗）。2022 年 6 月，Skyrizi（瑞莎珠单抗）作为首个靶向 p19 亚基的 IL-23 抑制剂在美国获批用于克罗恩病。2023 年 5 月，Rinvoq（乌帕替尼）在美国获批，但该药物被限定用于对一种或多种 TNF 阻滞剂不耐受患者的后线治疗，这导致 JAK 抑制剂无法用于一线治疗。

The current treatment paradigm adopts a two-phase approach, first using therapies to induce clinical remission in treating acute disease, followed by therapies to maintain response/remission. Treatment goals are to control inflammation, give rise to endoscopic mucosal healing, and prevent the occurrence of disease complications. Notably, the US Food and Drug Administration (FDA) is transitioning from using Crohn’s Disease Activity Index (CDAI) primary endpoints to patient-reported outcomes. Furthermore, endoscopic endpoints are becoming more integral to the regulatory assessment of drugs.
当前的治疗模式采用两阶段方法，首先使用疗法诱导临床缓解以治疗急性疾病，随后采用维持应答/缓解的疗法。治疗目标包括控制炎症、实现内镜下黏膜愈合，以及预防疾病并发症的发生。值得注意的是，美国食品药品监督管理局（FDA）正从使用克罗恩病活动指数（CDAI）主要终点转向患者报告结局。此外，内镜终点在药物监管评估中正变得越来越重要。

The American College of Gastroenterology (ACG), the American Gastroenterology Association (AGA), the European Crohn’s and Colitis Organisation (ECCO), and the UK’s National Institute for Health and Care Excellence (NICE) have produced treatment guidelines for the management of CD.
美国胃肠病学院（ACG）、美国胃肠病协会（AGA）、欧洲克罗恩病和结肠炎组织（ECCO）以及英国国家健康与护理卓越研究所（NICE）已制定了克罗恩病管理的治疗指南。

ACG treatment guidelines  ACG 治疗指南

The 2018 ACG guidelines provide recommendations for the treatment of mild-to-moderately severe disease/low-risk disease, moderate-to-severe disease/moderate-to-high-risk disease, and severe/fulminant disease.
2018 年 ACG 指南针对轻度至中度疾病/低风险疾病、中度至重度疾病/中高风险疾病以及重度/暴发性疾病提供了治疗建议。

AGA treatment guidelines  AGA 治疗指南

The 2021 AGA guidelines provide recommendations for the treatment of moderate-to-severe luminal and fistulizing CD.
2021 年 AGA 指南针对中重度管腔型和瘘管型克罗恩病的治疗提供了建议。

In 2023, a multidisciplinary panel consisting of content experts and guideline methodologists made the following conditional recommendations.
2023 年，由内容专家和指南方法学家组成的多学科小组提出了以下有条件建议。

2023 AGA guidelines on the role of biomarkers for the management of CD
2023 年美国胃肠病协会关于生物标志物在克罗恩病管理中作用的指南

ECCO treatment guidelines
ECCO 治疗指南

The 2024 ECCO guidelines provide recommendations for the induction of remission for mild-to-moderate disease and moderate-to-severe disease, as well as maintenance of remission.
2024 年 ECCO 指南针对轻中度及中重度疾病提供了诱导缓解和维持缓解的治疗建议。

2019 NICE treatment guidelines
2019 年 NICE 治疗指南

The 2019 NICE guidelines provide recommendations for inducing and maintaining remission.
2019 年 NICE 指南针对诱导和维持缓解提供了治疗建议

Last Reviewed:  最后审阅日期：
04 Mar, 2024  2024 年 3 月 4 日

by Ridwaan Ibrahim  作者：Ridwaan Ibrahim

Overview  概述

Methodology  方法论

We undertook market-specific literature reviews in order to provide a robust analysis of the diagnosed prevalent CD population in the US, Japan, and five major European markets. A variety of secondary data sources were identified, including literature reviews and epidemiological study reports, before quality appraisal, forming a robust foundation on which to model and forecast the patient population. Sources were evaluated for inclusion based on their epidemiological quality, including study settings, demographic sample profiles, sampling procedures and sample size, and potential sources of bias. Prevalence proportions were extracted, by age and gender where available, for diagnosed CD.
我们开展了针对特定市场的文献综述，旨在对美国、日本和欧洲五大主要市场中确诊克罗恩病（CD）的患病人群进行可靠分析。在质量评估前，我们识别了包括文献综述和流行病学研究报告在内的多种二手数据来源，为建模和预测患者群体奠定了坚实基础。数据源的筛选标准基于其流行病学质量，涵盖研究环境、人口样本特征、抽样流程与样本量以及潜在偏倚来源等因素。在可获得数据的情况下，我们按年龄和性别提取了确诊克罗恩病的患病率数据。

This analysis covers all ages, as CD can be diagnosed and prevalent at any age.
本分析涵盖所有年龄段人群，因为克罗恩病可在任何年龄阶段被确诊并普遍存在。

An overview of sources used is provided in the table below. Details on specific sources used for each country are given in the country-specific sections that follow.
下表概述了所使用的数据来源，后续各国具体章节将详细说明各国采用的数据来源细节。

Disease definition  疾病定义

There is no universal standard approach to CD diagnosis. Instead, diagnosis is based on a combination of endoscopic, histological, radiological, and/or biochemical investigations. For the purpose of this forecast, diagnosed CD cases were defined as follows:
目前尚无统一的克罗恩病诊断标准方法。诊断需结合内窥镜检查、组织学检查、影像学检查和/或生化检测结果。在本预测模型中，确诊的克罗恩病病例采用以下定义标准：

• International Classification of Diseases (ICD)-10 code K50.x.
  国际疾病分类（ICD）-10 编码 K50.x

• ICD-9 code 555.x.  ICD-9 编码 555.x。

• Cases identified using the diagnostic criteria set out by Lennard-Jones (1989) and recommended for use within the second European evidence-based consensus on the diagnosis and management of Crohn's disease (Van Assche et al., 2010). Diagnosis is confirmed by clinical evaluation and a combination of endoscopic, histological, radiological, and/or biochemical investigations (Lennard-Jones, 1989; Van Assche et al., 2010).
  病例采用 Lennard-Jones（1989 年）制定的诊断标准进行识别，该标准被推荐用于第二版欧洲循证共识中关于克罗恩病的诊断和管理（Van Assche 等人，2010 年）。诊断需通过临床评估结合内窥镜检查、组织学检查、影像学检查和/或生化检查来确认（Lennard-Jones，1989 年；Van Assche 等人，2010 年）。

• For populations using a health insurance provider as the sampling frame, individuals with at least one claim for CD who also had at least one pharmacy claim for an inflammatory bowel disease (IBD)-specific medication (University of Minnesota IBD Epidemiology Database definition; validated by Bernstein et al. [1999]).
  对于以健康保险提供商作为抽样框架的人群，个体需至少有一次克罗恩病（CD）的理赔记录，并至少有一次针对炎症性肠病（IBD）特异性药物的药房理赔记录（明尼苏达大学 IBD 流行病学数据库定义；经 Bernstein 等人[1999 年]验证）。

• Excluding CD diagnosed purely on the basis of genetic mutations. Currently, the measurement of genetic mutations in patients with CD remains a research tool that is not yet proven to be of clinical benefit for the general assessment of diagnosis, guidance of patient care, or prediction of response to specific medical therapies (Lichtenstein et al., 2018).
  排除仅基于基因突变诊断的克罗恩病。目前，对克罗恩病患者基因突变的检测仍是一种研究工具，尚未证明其对一般诊断评估、患者护理指导或特定药物治疗反应预测具有临床益处（Lichtenstein 等人，2018 年）。

• For studies where the specific diagnosis method was not described, primary or secondary care data describing a specific CD diagnosis were accepted.
  对于未描述具体诊断方法的研究，描述特定 CD 诊断的初级或二级医疗数据均可被接受。

Country-specific methods  国别研究方法

US  美国

To generate pediatric cases for CD, age- and gender-specific prevalence rates were extracted from Kappelman et al. (2013). We dynamically modeled age-specific prevalence rates instead of using a static model, employing an in-house VBA model. For the adult cases, age-specific prevalence rates reported by Loftus et al. (2007) were used as a guide for the shape of the curve. For all curves, we utilized a unimodal distribution of prevalence rates. The adult prevalence rate was calibrated to the rate provided by Weisman et al. (2023). The IBD gender ratio reported in the latter paper was applied to the diagnosed prevalence rate to generate gender-specific rates. Please note that the prevalence rate in the US reported in the literature varies due to the different methodologies used in the papers. For this analysis, we chose a source that uses the National Health and Nutrition Examination Survey (NHANES) as a data source. This ensures that we capture all patients, regardless of whether they are in remission, whereas sources that use medical claims databases might not include patients who are in remission, thus underestimating the size of the patient population.
为生成克罗恩病（CD）的儿科病例数据，我们从 Kappelman 等人（2013 年）的研究中提取了按年龄和性别划分的患病率。我们采用内部开发的 VBA 模型对年龄特异性患病率进行动态建模，而非使用静态模型。对于成人病例，则以 Loftus 等人（2007 年）报告的年龄特异性患病率作为曲线形态参考基准。所有曲线均采用单峰分布的患病率模型，其中成人患病率根据 Weisman 等人（2023 年）提供的数据进行校准。基于后者论文报告的炎症性肠病（IBD）性别比例，我们对确诊患病率进行性别分层计算。需特别说明的是，由于各文献采用的方法学差异，美国患病率数据在现有研究中存在较大波动。本分析选择以国家健康与营养调查（NHANES）为数据源的文献作为基准，这种设计能确保涵盖所有患者（包括缓解期病例），而采用医疗理赔数据库的研究可能遗漏缓解期患者，从而导致患者规模的低估。

Japan  日本

Gender-specific rates were derived from Murakami et al. (2019), who conducted a mail-based survey targeting hospitals to estimate the numbers of patients with ulcerative colitis and CD in 2014. Respondents were asked to report the number of patients meeting the diagnostic criteria for these conditions. The prevalence rate specific to CD was extracted from this paper; however, since age-specific rates were not reported, we used the age-specific rates provided in a US study as a reference to model the age-specific rates for Japan.
性别特异性发病率数据源自 Murakami 等人（2019 年）开展的邮件问卷调查，该调查以医院为对象估算 2014 年溃疡性结肠炎和克罗恩病（CD）患者数量。调查要求受访机构上报符合这两种疾病诊断标准的患者人数。本文从中提取了克罗恩病的特异性患病率数据；但由于未报告年龄别发病率，我们参考了美国某项研究提供的年龄别发病率数据来模拟日本的情况。

Although the data source used hospital data, it is worth noting that due to the severity of CD and the requirement for specialized treatment, omitting sample populations from other settings would not significantly impact the diagnosed prevalence rate reported for Japan.
尽管数据来源为医院资料，但值得注意的是：鉴于克罗恩病的严重性及需要专业治疗的特点，未纳入其他场景的样本人群并不会对日本报告的诊断患病率产生显著影响。

France  法国

Due to a lack of epidemiological papers reporting the prevalence of CD in France, Nerich et al. (2006) aimed to investigate the incidence of CD by geographical distributions. To calculate the prevalence rate using this source, we utilized the ratio of incidence to prevalence from a UK source (King et al., 2020); this was the only source that provided both incidence and prevalence rates of CD in one paper. By applying this ratio to the incidence rate reported by Nerich et al., we ensured the derivation of a country-specific prevalence rate. Various factors such as ethnicity, genetics, and lifestyle modifications can contribute to differences seen in prevalence rates across countries, hence the prevalence rate was not extrapolated from another country. In this calculation, we assumed that the survival expectancy for patients suffering from CD in both the UK and France is similar.
由于缺乏报告法国乳糜泻（CD）患病率的流行病学文献，Nerich 等人（2006 年）旨在通过地理分布调查 CD 的发病率。为利用该数据源计算患病率，我们采用了英国文献（King 等人，2020 年）中发病率与患病率的比值——这是唯一在同一篇论文中同时提供 CD 发病率和患病率的数据源。通过将该比值应用于 Nerich 等人报告的发病率，我们确保了推导出具有国家特异性的患病率。种族、遗传和生活方式改变等多种因素可能导致各国患病率存在差异，因此患病率并未从其他国家数据外推。在此计算中，我们假设英国和法国 CD 患者的预期生存期相似。

Germany  德国

Gender-specific rates were sourced from Hein et al. (2014), who estimated the one-year period prevalence of IBD in 2010 and investigated the actively treated prevalence of IBD. Specifically, we obtained the prevalence rate specific to CD from the study and applied it to our model. To establish age-specific rates, we used age rates from the US as a reference, and our model was calibrated to match the prevalence rate provided by Hein et al. Their study utilized an insurance-based cohort comprising between 265,102 and 311,001 individuals, with CD cases defined based on ICD-10 codes.
性别特异性数据来源于 Hein 等人(2014 年)的研究，该研究估算了 2010 年 IBD 的一年期患病率并调查了活动性治疗患病率。我们特别从该研究中获取了克罗恩病(CD)的特异性患病率数据并应用于模型。为建立年龄特异性数据，我们以美国的年龄分布率为参照，并通过模型校准使其与 Hein 研究提供的患病率相匹配。该研究采用基于保险的队列数据，样本量在 265,102 至 311,001 人之间，克罗恩病病例根据 ICD-10 编码进行定义。

Italy  意大利

Gender-specific rates were extracted from the study by Crocetti et al. (2021). Age-specific rates were extrapolated from the US. It is important to note that the paper from which the data were extracted may not be nationally representative, as individuals residing in Milan might have different risk factors compared to those in other regions of the country. Our estimation for approximately 97,500 patients in Italy in 2023 closely aligns with the reported number of patients in the paper (around 99,000). Differences between the estimates could be attributed to the different demographic population numbers used.
性别特异性数据源自 Crocetti 等人(2021 年)的研究。年龄特异性数据则根据美国数据进行推算。需特别说明的是，原始论文数据可能无法代表意大利全国情况，因为米兰居民的风险因素可能与其他地区存在差异。我们估算 2023 年意大利患者数约为 97,500 人，与论文报告的 99,000 人高度接近，差异可能源于采用的人口统计基数不同。

Spain  西班牙

Since no paper reported the prevalence rate of CD in Spain, we utilized a UK source that provided both incidence and prevalence rates of CD. By calculating the incidence to prevalence ratio from the UK data, we applied this ratio to the incidence rate reported by Chaparro et al. (2021) for Spain. The underlying assumption is that the survival expectancy of CD patients is similar across both countries. Additionally, age-specific rates from the US were used as a reference to generate age-specific rates for Spain.
由于缺乏西班牙乳糜泻(CD)患病率的公开文献，我们采用了同时包含发病率和患病率的英国数据源。通过计算英国数据中的发病率与患病率比值，将该比值应用于 Chaparro 等人(2021 年)报告的西班牙发病率数据。该方法基于两国 CD 患者预期生存期相似的假设。此外，西班牙的年龄特异性数据是参照美国的年龄分布模型进行推算的。

UK  英国

The data for the UK were calibrated to match the prevalence rate reported by King et al. (2020). Their study investigated cases of IBD between 2000 and 2018, utilizing a national primary care database to extract the number of cases. Gender-specific rates for CD were extracted from this source and incorporated into our model. Additionally, we employed a unimodal distribution, with the data peaking around the 25–39 years age group.
英国数据经过校准，以匹配 King 等人(2020 年)报告的患病率。该研究调查了 2000 至 2018 年间 IBD 病例情况，通过调用国家初级诊疗数据库提取病例数。克罗恩病的性别特异性发病率数据即源自该数据库，并被整合入我们的模型。此外，我们采用单峰分布模型，数据显示发病率峰值出现在 25-39 岁年龄组。

Forecasting  预测方法

To calculate the number of diagnosed prevalent cases of CD in the 2023–43 forecast period, we multiplied calculated prevalence proportions by the corresponding country-, age-, and gender-specific population estimates from the UN World Population Prospects database (United Nations, 2022). The UN database was chosen as a reliable population denominator; the data include standard sets of demographic indicators and populations by five-year age group and gender. The forecasted numbers of prevalent cases were validated against national benchmarks where possible, in order to check for any inconsistencies or unusual trends in the analysis.
为计算 2023-2043 年预测期内克罗恩病确诊现患病例数，我们将计算的患病比例与联合国《世界人口展望》数据库(United Nations, 2022)中各国分年龄、性别人口估算值相乘。选用联合国数据库作为可靠的人口基数来源，其数据包含标准人口统计指标及按五岁年龄组和性别划分的人口数。预测现患病例数在可能情况下均与国家基准数据进行校验，以排查分析中的异常趋势或不一致情况。

Last Reviewed:  最后审阅日期：
09 Oct, 2024  2024 年 10 月 9 日

by Joseph Jacob and Sonny Nghiem
作者：约瑟夫·雅各布与桑尼·阮

Overview   概述

The CD market will expand significantly over the 2024–33 forecast period, with sales in the US, Japan, and five major European markets growing from $13.6bn to $19.1bn at a compound annual growth rate (CAGR) of 3.87%. Although sales in all seven markets are set to increase over 2024–33, the fast-expanding US segment will be the major growth driver of the wider CD market.
2024-2033 年预测期内，CD 市场将显著扩张。美国、日本及欧洲五大主要市场的销售额将从 136 亿美元增长至 191 亿美元，复合年增长率（CAGR）达 3.87%。虽然七大市场在 2024-2033 年间均将实现增长，但快速扩张的美国市场将成为整个 CD 市场的主要增长驱动力。

Key themes  关键主题

[1] Despite all currently available key marketed brands facing generic/biosimilar competition in the US, Japan, and five major European markets during the forecast period, CD market expansion will be propelled by several launches of pipeline products and novel formulations of established drugs.
[1] 尽管当前所有主要上市品牌药在预测期内都将面临美国、日本及欧洲五大市场的仿制药/生物类似药竞争，但管线产品的陆续上市及已上市药物新剂型的推出将持续推动 CD 市场扩张。

[2] Stelara will face direct competition both from biosimilars and from competitor Skyrizi. Skyrizi offers a more selective mechanism of action, excellent remission rates, and a quick onset of efficacy, while it is also backed by AbbVie. Omvoh and Tremfya will also increase competition in this segment upon their respective launches later in the forecast period.
[2] 喜达诺（Stelara）将同时面临生物类似药和竞品 Skyrizi 的直接竞争。Skyrizi 凭借更具选择性的作用机制、优异的缓解率和快速起效优势（且获得艾伯维公司支持），将形成有力竞争。奥木禾（Omvoh）和特诺雅（Tremfya）也将在预测期后期相继上市，进一步加剧该领域竞争。

[3] Rinvoq is increasingly gaining popularity as the only approved oral agent in CD. AbbVie has extensive commercial resources and marketing experience with Humira, and is positioning Rinvoq and Skyrizi as its next-generation products to overcome losses from Humira’s biosimilar erosion.
[3] Rinvoq 作为克罗恩病（CD）领域唯一获批的口服制剂正日益受到青睐。艾伯维凭借修美乐积累了丰富的商业资源和营销经验，现正将 Rinvoq 和 Skyrizi 定位为下一代产品，以应对修美乐生物类似药冲击带来的损失。

[4] Biosimilars will play a large part in the CD space over the forecast period, with notable sales predicted for biosimilar versions of adalimumab, ustekinumab, and infliximab. Biosimilar versions of Humira have already entered the US market, with biosimilars to Stelara expected in late 2024/early 2025, and substantial market deterioration is expected for the branded versions.
[4] 生物类似药将在预测期内占据克罗恩病治疗领域的重要份额，阿达木单抗、乌司奴单抗和英夫利昔单抗的生物类似药预计将实现显著销售额。修美乐生物类似药已进入美国市场，而斯特拉拉的生物类似药预计将于 2024 年底/2025 年初上市，原研品牌药的市场份额预计将大幅萎缩。

Methodology  方法论

We use a patient-based approach to size the commercial potential of the CD market across the US, Japan, and five major European markets. This analysis contains an assessment of key CD therapies on the market and in the late-phase pipeline, a discussion of CD market dynamics, and a 10-year patient-based sales forecast.
我们采用基于患者数量的方法评估美国、日本及欧洲五大主要市场的克罗恩病商业潜力。该分析包括对已上市及后期研发阶段关键疗法的评估、克罗恩病市场动态的探讨，以及基于患者数量的十年销售预测。

Q3 2024 model updates  2024 年第三季度模型更新

• Forecast period extended to 2033
  预测期延长至 2033 年

• Epidemiology updated  流行病学数据已更新

• RHB-104 removed from the forecast
  RHB-104 已从预测中移除

• Brazikumab removed from the forecast
  Brazikumab 已从预测中移除

• Rinvoq moved from pipeline to marketed drugs
  Rinvoq 已从研发管线转入上市药物

• Alofisel market share removed from the US and slightly increased in the EU
  Alofisel 市场份额在美国市场撤出，在欧盟市场略有提升

• Cimzia sales adjusted slightly higher
  Cimzia 销售额小幅上调

• Entyvio sales split into Entyvio and Entyvio SC
  Entyvio 销售额拆分为 Entyvio 和 Entyvio SC 两个条目

• Humira discounts and rebates adjusted according to biosimilar competition
  根据生物类似药竞争情况调整了 Humira 的折扣与返利政策

• Skyrizi sales adjusted higher
  Skyrizi 销售额预期上调

• Stelara sales adjusted lower
  Stelara 销售额预期下调

• Tysabri sales adjusted slightly lower
  Tysabri 销售额预期微幅下调

• Biosimilar adalimumab pricing averaged on currently available biosimilars
  生物类似药阿达木单抗定价基于现有生物类似药平均水平

• Biosimilar infliximab sales adjusted slightly lower
  生物仿制药英夫利昔单抗销售额小幅下调

• Mirikizumab branded as Omvoh and sales adjusted lower
  米利珠单抗（商品名 Omvoh）销售额下调

• Tremfya sales adjusted slightly higher
  特诺雅销售额小幅上调

• Zeposia sales adjusted lower
  泽布西亚销售额下调

• Biosimilar ustekinumab sales adjusted higher.
  乌司奴单抗生物类似药销售额预期上调

Q1 2023 model updates  2023 年第一季度模型更新

• Forecast extended to 2032
  预测期延长至 2032 年

• Jyseleca forecast removed
  移除 Jyseleca 预测数据

• Etrolizumab forecast removed
  移除 Etrolizumab 预测数据

• Alofisel sales adjusted slightly higher
  Alofisel 销售额微幅上调

• Entyvio sales adjusted slightly higher
  Entyvio 销售额微幅上调

• Humira sales adjusted lower
  Humira 销售额下调

• Remicade sales adjusted slightly lower
  Remicade 销售额微幅下调

• Skyrizi sales adjusted slightly higher
  Skyrizi 销售额小幅上调

• Tysabri sales adjusted slightly higher
  Tysabri 销售额微幅上调

• Biosimilar adalimumab sales adjusted higher
  生物类似药阿达木单抗销售额调高

• Biosimilar infliximab sales adjusted slightly higher
  生物类似药英夫利昔单抗销售额小幅上调

• Skyrizi moved to marketed drugs
  Skyrizi 转入上市药物行列

• Biosimilar adalimumab (Amjevita) pricing added
  新增生物类似药阿达木单抗（Amjevita）定价信息

• Zeposia launch year changed from 2023 to 2024 in US, and from 2023 to 2025 in EU.
  Zeposia 在美国的上市年份从 2023 年调整为 2024 年，在欧盟从 2023 年调整为 2025 年

• Brazikumab launch year changed from 2027 to 2028
  Brazikumab 的上市年份从 2027 年调整为 2028 年

• Mirikizumab launch year changed from 2023 to 2024
  Mirikizumab 上市年份从 2023 年调整为 2024 年

• Zeposia loss of exclusivity dates added in US and EU
  Zeposia 在美国和欧盟的专利独占期失效日期已添加

• Entyvio patent expiry year updated from 2024 to 2025 in EU
  Entyvio 在欧盟的专利到期年份从 2024 年更新为 2025 年

• Entyvio patent expiry date updated to July 2028 in Japan
  Entyvio 在日本的专利到期日期更新为 2028 年 7 月

• Biosimilar vedolizumab launch delayed to 2032.
  生物类似药维多珠单抗上市推迟至 2032 年

Q4 2020 post-earnings model updates (1 April 2021)
2020 年第四季度财报后模型更新（2021 年 4 月 1 日）

• Forecast extended to 2030
  预测期延长至 2030 年

• Product sales updated with company-reported figures
  产品销量数据更新为公司报告值

• 2021 pricing updated  2021 年定价方案更新

• RHB104 forecast removed  已移除 RHB104 预测

• Mirikizumab US approval date pushed back
  米利珠单抗美国获批日期延后

• Entyvio forecast adjusted slightly higher
  Entyvio 销售预测微幅上调

• Remicade forecast adjusted slightly higher
  Remicade 销售预测微幅上调

• Stelara forecast adjusted higher
  Stelara 销售预测上调

• Biosimilar infliximab forecast adjusted higher
  英夫利昔单抗生物类似药销售预测上调

• Mirikizumab forecast adjusted lower
  米利珠单抗预测值下调

• Rinvoq forecast adjusted slightly higher
  乌帕替尼预测值微幅上调

• Tremfya forecast adjusted slightly higher
  特诺雅预测值微幅上调

• Zeposia forecast adjusted slightly higher
  泽布妥单抗预测值微幅上调

• Biosimilar ustekinumab forecast adjusted lower
  乌司奴单抗生物类似药市场预测下调

• Biosimilar vedolizumab forecast adjusted lower.
  维多珠单抗生物类似药市场预测下调

Model updates (18 December 2020)
模型更新（2020 年 12 月 18 日）

• Rinvoq forecast adjusted lower
  瑞福乐（Rinvoq）市场预测下调

• Jyseleca launch dates delayed and forecast adjusted lower.
  Jyseleca 上市日期推迟，预期销售额下调。

Q3 2020 post-earnings model updates (20 November 2020)
2020 年第三季度财报后模型更新（2020 年 11 月 20 日）

• Cimzia forecast adjusted slightly lower
  Cimzia 销售额预期微幅下调

• Stelara forecast adjusted slightly lower
  Stelara 销售额预期微幅下调

• Entyvio forecast adjusted slightly higher
  Entyvio 销售预测小幅上调

• Humira forecast adjusted slightly higher
  Humira 销售预测小幅上调

• Remicade forecast adjusted slightly lower
  Remicade 销售预测小幅下调

• Tremfya forecast added.  新增 Tremfya 销售预测

Clinical performance is important in driving a product’s success in CD; however, the overriding differentiator between products is market access. Market access carries the most weight within the commercial attributes of our drug assessment model, alongside size of target population. As specialty products, therapies for CD can be expensive, and formulary positioning is paramount to product uptake. Payers are settled in vital contracts that lead them to prioritize broad immunology drugs Humira and Remicade. This has posed a high barrier to newer entrants to the market, which cannot compete in volume and rebates. Biosimilar and generic competition will further undermine the likely premium pricing of newer drugs and pipeline products. 

Biologic disease-modifying antirheumatic drugs (DMARDs)
生物类疾病修饰抗风湿药物（DMARDs）

Anti-TNF inhibitors  抗肿瘤坏死因子抑制剂

Although the anti-TNF class possesses a stronghold at the first line of biologic therapy in the CD treatment algorithm, approximately a third of anti-TNF-naïve patients have a primary non-response to anti-TNF therapy, while another third are secondary non-responders (initial anti-TNF responders who lose their response or become intolerant). These drugs are favored due to long-standing physician familiarity and deep discounts/rebates that are conducive to prioritization in formularies; however, they are inadequate in satisfying persisting unmet needs in the CD market. Thus, they do not feature among the highest scoring for clinical attractiveness in our drug assessment model. 

Of the class, Johnson & Johnson’s Remicade (infliximab) scores the highest, despite already facing biosimilar competition. This is on account of its strong efficacy and differentiated, broad label, as it is approved to reduce the number of draining enterocutaneous and rectovaginal fistulas and to maintain fistula closure in adult patients with fistulizing CD. Although biosimilar uptake has risen, especially of Pfizer’s Inflectra, payers are still preferring Remicade as the pricing of biosimilars, which also include Renflexis and Avsola, is not low enough to warrant switching.  Furthermore, Remicade benefits from the extensive commercial resources and marketing experience of Johnson & Johnson, Merck & Co., and Mitsubishi Tanabe. However, this trend could be set to change following the approval of Celltrion's subcutaneous infliximab, Zymfentra, in October 2023. Although Inflectra is an infliximab biosimilar that references Remicade, Zymfentra was approved through the stand-alone biologics license application process. It is considered a new drug due to its regulatory pathway under section 351(a). It has patent protection through 2037 for its dosage form and 2040 for its route of administration. Zymfentra has favorable formulary positioning, following an agreement with Express Scripts and Cigna healthcare. This agreement provides Zymfentra with preferred brand access on the Express Scripts National Preferred Formulary and Cigna National Formulary, which together serve over 40 million insured lives in the US.  

A systematic review and meta-analysis by Singh et al. (2018) found that Remicade and Humira (adalimumab) were ranked highest for induction of clinical remission in biologic-naïve patients. In another meta-analysis conducted by Barberio et al. (2023), infliximab was ranked first for induction of clinical remission in all patients with luminal CD, but Skyrizi was ranked first for both biologic-naïve and biologic-exposed patients while Rinvoq once daily ranked first for maintenance of remission. Thus, these products have been assigned higher clinical scores than UCB’s Cimzia (certolizumab pegol). Commercially, Cimzia is further limited in only securing approval to treat CD in the US, unlike Humira and Remicade which are both approved to treat CD in the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). 

While Cimzia’s patent expired in February 2024, there are no biosimilar candidates at the clinical stage for certolizumab. 

“There was a phase in time when we had limited options when we were using a lot of certolizumab in Crohn’s, but it was usually third or fourth or fifth line. There’s definitely a perception that its efficacy is less than adalimumab’s and infliximab’s, and it probably works best when you use it earlier, like in first-line therapy, but for a variety of reasons I don’t use much certolizumab anymore. I used a lot more of it before 2014. When vedolizumab came out, and then a couple of years later ustekinumab came out, then we had enough options that we wouldn’t go through all three anti-TNFs before moving on. So, yes, I used way more certolizumab 10 years ago compared to now.” – US key opinion leader 

“Well, Cimzia was kind of dead on arrival. So, Cimzia was never really approved in Europe, and it is mostly used from what I understand in the US, and even there I think it has a very low market share. So, the problem is efficacy really, and then, now more recently we have learned that if you PEGylate medications, the PEG component becomes one of those eternal chemical compounds that accumulate themselves and may have a lot of long-term side effects. So, I think that's a big problem, and that's why Cimzia has never been on my list“ - Germany Key Opinion Leader 

Biosimilars to Humira  修美乐生物类似药

Since January 2023, when biosimilars to Humira began to enter the US market, these products have continued to vie for market share across immune and inflammatory disease areas. Biosimilar adalimumab entry represents a key inflection point in the US market, so we have included an overview of this landscape; however, individual biosimilars have been excluded from the drug assessment model.
自 2023 年 1 月修美乐生物类似药开始进入美国市场以来，这些产品持续在免疫和炎症疾病领域争夺市场份额。阿达木单抗生物类似药的上市标志着美国市场的关键转折点，因此我们对此格局进行了概述；不过具体生物类似药品种并未纳入药物评估模型。

The market dynamics of adalimumab biosimilar has change rapidly in the past two year. Key differentiator among these biosimilars is reimbursement coverage by pharmacy benefit managers (PBMs) while launch dates, concentration, interchangeability status, pricing strategies,  and commercial partnerships with distributors seem to play a minor role. In April 2024, CVS Caremark, one of the largest US PBMs, became the first PBM to remove Humira from its national preferred formulary, replacing it with biosimilar adalimumab versions. Following this trend, in 2025, OptumRx became the only major PBM to include Humira, but it dropped  the drug to Tier 3, requiring additional justification for prescriptions. Of note, unbranded adalimumab biosimilars are included in CVS Caremark and Express Scripts’ national preferred formulary (NPF).  In the midst of the coverage shuffle, Humira’s market position has begun to weaken as biosimilar adalimumab products makes further inroads.  Nevertheless, Humira still occupies roughly two thirds of the adalimumab market in the US. Among the approved adalimumab biosimilars, Hyrimoz has gained substantial traction, accounting for around 15% of the adalimumab market, facilitated by its partnership with Cordavis, a CVS subsidiary that pushed for its inclusion in the Caremark preferred formulary. 

Speed to market  快速上市

In early 2023, Amgen's Amjevita was the first biosimilar launched in the US as it was already a top-selling adalimumab option in Europe. Within the same year, Hyrimoz, Cyltezo, Hadlima, Hulio, Yusimry, Yuflyma, Idacio, and Abrilada entered the US market.
2023 年初，安进的 Amjevita 作为首个在美国上市的同类产品率先登陆，该药在欧洲已是热销的阿达木单抗选择。同年，海芮莫兹、Cyltezo、Hadlima、Hulio、Yusimry、Yuflyma、Idacio 和 Abrilada 相继进入美国市场。

Alvotech’s Simlandi was the last biosimilar adalimumab to enter the US market in February 2024 after the resolution of manufacturing issues inspected by the FDA. Its high-concentration formula with interchangeability gives Simlandi a competitive edge among its peers. Following Alvotech’s partnership with Teva, Simlandi has been included in Express Scripts’ preferred formulary in 2025.
阿尔沃泰克的 Simlandi 因生产问题经食品药品监督管理局审查通过后，于 2024 年 2 月作为最晚进入美国市场的阿达木单抗生物类似药上市。其高浓度配方与可互换性赋予该产品同业竞争优势。随着阿尔沃泰克与梯瓦制药达成合作，Simlandi 已被纳入 2025 年 Express Scripts 优先处方集。

Interchangeability and concentration
互换性与集中度

While the extent of the value of an interchangeability designation for adalimumab biosimilars remains to be seen, Cyltezo was the first biosimilar approved as interchangeable with Humira. The designation allows branded Humira to be replaced by the biosimilar at the pharmacy level without prior approval from the prescribing physician, subject to state laws. In addition to Cyltezo, five more biosimilars have been granted interchangeability designation, including Amjevita, Hyrimoz, Hadlima, Abrilada, and Simlandi.
虽然阿达木单抗生物类似药获得可互换性认定的实际价值仍有待观察，但 Cyltezo 是首个被批准可与 Humira 互换的生物类似药。该认定允许在药房层面用生物类似药替代原研 Humira，无需处方医生事先批准（具体依各州法律而定）。除 Cyltezo 外，另有五款生物类似药获得可互换性认定，包括 Amjevita、Hyrimoz、Hadlima、Abrilada 和 Simlandi。

Although the high-strength formula (100mg/mL) makes up the majority of the Humira market, many approved biosimilars are provided only at low concentration – half the strength. While Amjevita, Cyltezo, Hadlima and Hyrimoz launched at both concentrations, Hulio, Yusimry, Idacio and Abrilada only offer a low-concentration version. Both Simlandi and Yuflyma are approved only at the higher strength. Of note, Hyrimoz and Simlandi offer high-concentration formulations attached with interchangeability, providing an option with reduced injection volume. 

Pricing and market access strategies
定价与市场准入策略

Among the approved biosimilars, four (Amjevita, Hyrimoz, Yuflyma and Abrilada) are listed at a dual price and four (Cyltezo, Hulio, Idacia and Simlandi) are attached with low discount price while the other two (Hadlima and Yusimry) tagged at a high discount. Drugs with a single-digit discount price allows room for rebates, which would appeal to PBMs, while drugs with a large discount (80% or lower than Humira’s list price) can still compete in the market for uninsured, underinsured, or cost-sensitive patients who are likely to hit their deductible.
在获批的生物类似药中，四款（Amjevita、Hyrimoz、Yuflyma 和 Abrilada）采用双重定价策略，四款（Cyltezo、Hulio、Idacia 和 Simlandi）标注为低折扣价格，另有两款（Hadlima 和 Yusimry）标记为高折扣。个位数折扣价格的药品留有返利空间，这对药品福利管理公司具有吸引力；而大幅折扣（低于修美乐定价 80%或更多）的药品仍可在面向自费患者、医保不足者或费用敏感型患者的市场中保持竞争力——这类患者往往需要自行承担免赔额。

The adalimuamb market has changed rapidly and dramatically in the US in the initial years of biosimilar competition. In 2024, national formularies included several branded adalimumab biosimilars while starting to exclude Humira. In 2025, payers’ interest has shifted from branded biosimilars to unbranded products, which are included in the formularies of the top two PBMs covering over half of the prescriptions in the US. Only a handful of branded biosimilars (Amjevita, Hyrimoz, Cyltezo and Simlandi) are  included in the latest formularies from the top three PBMs in 2025. The largest PBM, CVS Caremark, covers three adalimumab biosimilars (Hyrimoz, Hadlima and Sandoz’ unbranded biosimilar), although these come with restrictions including prior authorization, quantity limits, and specialty drug  with higher criteria and more clinical review. While Express Scripts prefers Cyltezo, Simlandi and unbranded biosimilars provided by Sandoz, Boheringer and Qallent, OptumRx only includes Amjevita in Tier 2 and pushes Humira to Tier 3. Half of the branded biosimilars (Hulio, Yusimry, Yuflyma, Idacio, Abrilada) are not listed in these major formularies and may struggle to find ground in this ever-evolving market.
在美国生物类似药竞争初期，阿达木单抗市场经历了快速而剧烈的变化。2024 年，国家处方集已纳入多个品牌阿达木单抗生物类似药，同时开始将修美乐排除在外。到 2025 年，支付方的关注点从品牌生物类似药转向非品牌产品——这些产品已被覆盖全美过半处方的两大药房福利管理公司纳入处方集。2025 年三大顶级 PBM 最新处方集中，仅收录少数品牌生物类似药（安健宁、海正锐澳、赛妥珠单抗和欣普尼）。最大 PBM 机构 CVS Caremark 覆盖三种阿达木单抗生物类似药（海正锐澳、哈迪玛及山德士非品牌生物类似药），但设有事先授权、用量限制等使用条件，且作为专科药物需满足更高标准的临床审查。Express Scripts 优先选用赛妥珠单抗、欣普尼及山德士/勃林格殷格翰/Qallent 提供的非品牌生物类似药，而 OptumRx 仅将安健宁列入二级目录，并将修美乐降至三级目录。 半数品牌生物类似药（Hulio、Yusimry、Yuflyma、Idacio、Abrilada）未被纳入这些主要医保目录，在这个快速变化的市场中可能难以立足。

Coherus made headlines with its partnership with the Mark Cuban Cost Plus Drug Company, offering Yusimry at  steep discount of over 90% to SmithRx and RxPreferred members. However, without a high-price option to lend decent rebates to traditional PBMs that control most of the market, this retail strategy is not expected to gain significant market share. It is unlikely that insured patients would pay hundreds of dollars out of pocket for Yusimry when an alternative version of adalimumab would be covered. Consequently, in 2024, Coherus has opted to divest Yusimry to Meitheal Pharmaceuticals, a subsidiary of Hong Kong King-Friend Industrial Co., for an upfront cash payment of $40 million. This move marks Coherus as the first adalimumab biosimilar manufacturer to withdraw from this highly competitive sector.
Coherus 公司因与马克·库班成本加成制药公司合作而成为头条新闻，向 SmithRx 和 RxPreferred 会员提供折扣幅度超过 90%的 Yusimry。然而，由于缺乏高价选项来为控制大部分市场的传统药品福利管理者提供可观返利，这种零售策略预计难以获得显著市场份额。当其他阿达木单抗替代品可获医保覆盖时，投保患者不太可能自费数百美元购买 Yusimry。因此，2024 年 Coherus 选择将 Yusimry 以 4000 万美元首付款出售给香港金友工业有限公司旗下子公司 Meitheal Pharmaceuticals。此举使 Coherus 成为首个退出这一高竞争领域的阿达木单抗生物类似药生产商。

“I believe that biosimilars work exactly the same as originator molecules, they are cheaper, they’re no different in their administration. So, as far as my practice goes, whenever there is a biosimilar available, if it’s significantly cheaper and I can treat more patients with the biosimilar, I will certainly switch to a biosimilar.” – UK gastroenterology key opinion leader
"我认为生物类似药与原研分子完全等效，价格更便宜，给药方式也毫无差异。因此在我的临床实践中，只要存在可用的生物类似药，若其价格显著降低且能让我治疗更多患者，我一定会改用生物类似药。"——英国胃肠病学领域关键意见领袖

“I think they will help to bring the price down because it is competition.” – US gastroenterology key opinion leader 

US landscape of biosimilars to Humira 

Anti-integrin therapies  抗整合素疗法

Biogen’s Tysabri (natalizumab) features as a poorly rated candidate in the CD market both clinically and commercially. Its weaknesses lie with the treatment-related risk of serious safety issues, its limited geographic reach, and its poor formulary positioning. In Europe, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion on the marketing authorization of Tysabri to treat CD due to its unfavorable benefit/risk profile. Ultimately, Tysabri’s modest efficacy and the risk of progressive multifocal leukoencephalopathy (PML) limit its use. Even with the introduction of a JC virus immunoassay test to evaluate PML risk, uptake in CD has been limited. The John Cunningham virus (JCV) is a common infection and between 40-90% of the general population have been exposed to JC virus. PML is a disabling and potentially fatal neurological syndrome caused by the JCV that can occur in the setting of severe immunosuppression as seen in patients treated with Tysabri. 

Takeda’s Entyvio (vedolizumab) is an integrin antagonist binding to the T-cell integrin known as α4β7. Unlike Tysabri, which binds to both α4β7 and α4β1 integrin heterodimers, the selective binding of Entyvio to α4β7 prevents the migration of immune response-mediating T cells to the gastrointestinal tract and diminishes the various T-cell-mediated processes underlying CD and ulcerative colitis (UC). This selectivity, with the added convenience of a subcutaneous formulation, ensures Entyvio’s position among the safest approved agents for the treatment of CD, which has led to it gradually finding a favorable formulary position in the market. Although both Tysabri and Entyvio share common mechanisms of action, the former does not have a black box warning or increased risk of patients developing PML. In a meta-analysis conducted by Solitano et al. (2023) of 20 head-to-head studies in CD, there was no difference in the risk of serious infections between patients treated with Entyvio and those treated with anti-TNFs. 

Takeda, partnering with Roche and Royalty Pharma, has initiated the Phase III VICTRIVA trial in early 2025 to investigate the short- and long-term efficacy and safety of dual-targeted therapy with intravenous Entyvio and oral upadacitinib compared with intravenous vedolizumab monotherapy in moderate to severe adult CD patients. While several studies have been conducted using advanced combination therapies (ACT) involving two or more biologics or small molecules in treating CD, most of them are retrospective trials involving only a handful of patients. This randomized, double-blind, placebo-controlled study will be among the largest Phase IIIb trials to compare ACT in CD. 

In another effort to extend Entyvio’s lifecycle, Takeda acts as the industry lead in a multi-collaborative global study called the INTERCEPT project. This initiative aims to identify clinically validated biomarkers that can predict the onset of CD and 80 patients with the highest risk of developing the disease will receive Entyvio to prevent full-blown disease from developing. Following findings from the LOVE-CD trial, which showed Entyvio yields better outcomes and has a better safety profile in early CD than in those with late disease, if the INTERCEPT project successfully identifies accurate biomarkers, Entyvio could find itself in a privileged spot of being available as a preventive measure. 

“I don’t use it much. I probably have maybe 5% in Crohn’s disease, I think initially when it first came out, I used a lot of it in Crohn’s because we had a lot of patients that had run out of other options, and many of those patients are no longer on vedolizumab, they are on other drugs because there’s just a perception that it doesn’t work as well in Crohn’s, and I think that’s true. I use it way more in ulcerative colitis than I do in Crohn’s.” – Italy gastroenterology key opinion leader 

Anti-interleukin therapies
抗白细胞介素疗法

Johnson & Johnson’s Stelara (ustekinumab) scores the second highest clinically out of all the marketed drugs in our assessment model, only below the more recently approved Skyrizi. In a systematic review and meta-analysis by Singh et al. (2018), Stelara was found to have the lowest risk of serious adverse events and infection in maintenance trials and was further ranked the highest for induction of clinical remission in patients with prior anti-TNF exposure. Another systematic review with meta-analysis conducted by Attauabi et al. (2021) found encouraging efficacy data for Stelara on fistulizing perianal CD, which occurs in as many as 50% of CD patients. In the Phase IIIb SEAVUE trial (ClinicalTrials.gov identifier: NCT03464136), Stelara did not show statistical superiority versus adalimumab on the primary endpoint of clinical remission. Nevertheless, statistically significant separation from adalimumab was achieved for secondary endpoints, including the maintenance of clinical response at week 52 in patients with clinical response at week 16 (88.6% vs. 78%; p<0.016), as well as other liquid/soft stool endpoints. Pooled long-term safety results released in early 2023 through five years continued to support the drug’s well-established safety profile. Commercially, its prospects are limited by its US patent expiry, which has now begun, as well as its relegation behind anti-TNF therapies in formularies. 

Stelara has been used off-label for pediatric use in both the US and the EU. Although biosimilar versions are not expected to come with a pediatric approval in CD, they will be expected to share the off-label usage space in CD. Eyeing this market, Johnson & Johnson have filed for a supplementary approval in pediatric CD in the EU. 

In the final three months of 2024, Stelara sales dropped by 14.7% to $2.35bn, with international sales plummeting by almost a third – down 32.7% at $650m – in the face of European biosimilar competition. Meanwhile, US sales slid by 4.9% to $1.70bn. 

Biosimilars to Stelara  Stelara 生物类似药

Among the several ustekinumab biosimilars, seven have been approved late in 2024 in the US. Amgen’s Wezlana (ABP654) received approval, with interchangeability designation, from the FDA in November 2023, making it the first approved biosimilar of Stelara in the US. Wezlana also gained a marketing authorization in the EU in July 2024 and launched in the US on 1 January 2025, making it the first Stelara biosimilar in the US market. In the US, Wezlana is available only through Optum, a division of UnitedHealth Group. 

In contrast to adalimumab biosimilars Cyltezo and Abrilada, the FDA's decision on Wezlana's interchangeability designation did not rely on switching studies, although Amgen conducted such a study alternating Stelara and Wezlana in psoriasis patients. This deviated from the 2019 interchangeability guidance, which required switching study data. The FDA waived the need for a switching study for Wezlana because the drug demonstrated similar safety and effectiveness profiles to Stelara through comprehensive analyses, including chemical and biological tests, comparative pharmacokinetics, efficacy, safety, and immunogenicity data in humans. Wezlana is not the first biosimilar to be granted interchangeability without a switching study. Other examples, such as Lantus biosimilars (Semglee and Rezvoglar) and Lucentis copycats (Cimerli and Byooviz), received this designation based on sufficient justification and robust scientific evidence. While Wezlana's case may not directly apply to other ustekinumab biosimilars, this regulatory trend is expected to stimulate and expedite the approval of more biosimilars across various drug classes and diseases. The FDA's planned revision of its interchangeability guidance further supports this prospect. 

Following the resolution of the CRL issued in 2023, Alvotech and Teva’s Selarsdi (Uzpruvo or AVT04) gained FDA’s approval in April 2024 and the drug was launched on 21 February 2025 becoming the second ustekinumab biosimilar on the US market. Its interchangeability status is anticipated after Amgen’s biosimilar exclusivity expires. Additionally, Selarsdi has achieved regulatory success in other continents, including approval from the Japanese regulatory authority in September 2023 and, in collaboration with Stada, approval in the EU in January 2024. 

Sandoz has finalized a deal with Samsung Bioepis for the commercial rights to the ustekinumab biosimilar Pyzchiva (SB17) in the US and other regions, following their collaboration on Hadlima. Pyzchiva received marketing authorization from the European Commission (EC) in April 2024 and FDA approval in July 2024. Sandoz revealed that it had secured a partnership with an undisclosed PBM for a private-label version, similar to the firm’s partnership with CVS’s Cordavis for its Hyrimoz (biosimilar adalimumab). Following the launch of Pyzchiva this year, Johnson & Johnson were quick to file a lawsuit against Samsung Bioepis citing violation of the terms of the original settlement from 2023. Johnson & Johnson stated that the litigation is targeted to prevent improper sublicensing of a second, additional product to a PBM’s private label distributor and not towards Samsung from commercializing Pyzchiva, casting uncertainties to Pyzchiva in the near future 

Several strategic collaborations have taken place to commercialize ustekinumab biosimilars. Intas Pharmaceuticals (India) has joined the alliance of Dong-A Socio Holdings (South Korea) and Meiji Seika Pharma (Japan) that has co-developed Imuldosa (Absimky or DMB-3115). In October 2024, in addition to receiving the FDA approval, Imuldosa also received a positive opinion by Committee for Medicinal Products for Human Use (CHMP) under two brand names Imuldosa and Absimky for the European market with identical labels except for the former one omitting ulcerative colitis in its list of indications. Formycon and Fresenius Kabi have reached an agreement with Johnson & Johnson to launch Otulfi (Fymskina or FYB202), which was approved in the US and EU in September 2024. Although they partnered for commercialization, they submitted separate marketing authorization applications in the EU, both receiving positive opinions from the CHMP in July 2024. In the European market, Formycon's Fymskina covers all indications approved for Stelara, while Fresenius Kabi's Otulfi does not include ulcerative colitis. Both Otulfi and Fymskina are now launched in the respective markets with the former being the latest to join a host of Stelara biosimilars in the US. 

As the biosimilar landscape continues to evolve, several key players are making significant strides in the development and approval of ustekinumab biosimilars. Celltrion’s Steqeyma (CT-P43) received FDA approval and has a launch date set for March 7, 2025. Additionally, Steqeyma has received marketing authorization from the EC in September 2024, becoming the fourth ustekinumab biosimilar in the EU. Biocon’s Yesintek (Bmab1200) received approval from the FDA in November 2024. Following a settlement and license agreement with Janssen, the drug has launched the drug in the US in February 2025.  In 2022, Biocon entered into a strategic out-licensing deal with Yoshindo (Japan) to commercialize Bmab 1200 in Japan. In July 2024, Bio-Thera, a company based in China, announced that its proposed interchangeable biosimilar to Stelara, BAT2206, has been accepted by several regulatory agencies, including the FDA, EMA, and the China National Medical Products Administration (NMPA). 

China's Jiangsu Qyuns Therapeutics formed a collaboration agreement with Huadong Medicine to commercialize its copycat of Stelara, QX001S, in China and launched the product on February 12, 2025.  In July 2023, Indian firm Aurobindo Pharma joined this battle via its subsidiary CuraTeQ Biologics by inking an exclusive licensing deal with US-based BioFactura to commercialize BFI-751 in major markets such as the US, EU, and UK. BioFactura plans to initiate a global Phase III trial soon. 

Unlike Humira which was not chosen for price negotiations under the Inflation Reduction Act (IRA), Stelara and its biosimilars will be affected by the IRA with the brand’s negotiated price taking effect from 2026. The IRA states that while a price control is in effect for the brand, the brand will be guaranteed formulary coverage (even if a biosimilar or generic is on the market with a lower cost). There is an exception to this ruling stated under CMS’ draft CY2025 Part D Redesign Program Instructions which state that if a newly available, therapeutically equivalent generic drug is added to the formulary at the same time as a brand with  maximum fair price (MFP), then the brand can be removed from the formulary or the brand’s preferred or tiered cost-sharing status can be changed. This will not affect the currently launched biosimilars as they will have to compete with Stelara for formulary positioning. However, if a biosimilar’s launch is delayed to June 2025 (typically when 2026 formularies are determined), formularies could directly substitute the new biosimilar and remove coverage for the brand entirely. This will negatively affect both Stelara and currently launched ustekinumab biosimilars. 

With Stelara prices to be cut down 66% from 2026 subject to MFP due to the IRA , biosimilar companies are offering huge discounts to Stelara. Amgen is opting for a dual discount strategy for Wezlana compared to Stelara. Biocon’s Yesintek will have a wholesale acquisition cost of $3000, reflecting a 90% discount to Stelara, making it the lowest-priced ustekinumab biosimilar launched till date. These competitive pricing strategies will likely affect Imuldosa which is expected to launch later in the Q2 2025. In light of the aggressive pricing strategies from competitors, Formycon lowered its Stelara biosimilar Otulfi’s asset value by a third from $370m to $100m having launched the drug at an 85% discount to the brand. 

US landscape of biosimilars to Stelara
美国 Stelara 生物类似药市场格局

Other interleukin inhibitors
其他白细胞介素抑制剂

Skyrizi (risankizumab) is the first IL-23 inhibitor targeting the p19 subunit to be approved for CD. With positive results from the open-label Phase III SEQUENCE trial, Skyrizi has positioned itself as the highest clinically scoring drug in the CD market. The trial pitted Stelara against Skyrizi, with the latter coming out on top. Of the two primary endpoints, Skyrizi demonstrated non-inferiority on clinical remission at week 24 and showcased superiority over Stelara on endoscopic remission at week 48, reinforcing the selective mechanism of action of targeting the p19 subunit of IL-23 over Stelara’s IL-12 and IL-23 inhibition. These results will also have a positive impact on other pipeline products such as Omvoh and Tremfya, which are both targeting a similar mechanism of action as Skyrizi and are expected to offset Stelara biosimilars that have now launched in 2025..
Skyrizi（瑞莎珠单抗）是首个获批用于克罗恩病治疗的靶向 IL-23 p19 亚基抑制剂。凭借开放标签 III 期 SEQUENCE 试验的积极结果，该药物已成为克罗恩病市场临床评分最高的治疗药物。这项头对头试验中，Skyrizi 在与 Stelara 的对比中胜出：在两项主要终点指标上，Skyrizi 不仅在第 24 周达到临床缓解的非劣效性标准，更在第 48 周的内镜缓解率上显著优于 Stelara，这强化了其选择性靶向 IL-23 p19 亚基的作用机制相较于 Stelara 双重抑制 IL-12/IL-23 的临床优势。该试验结果还将对 Omvoh 和 Tremfya 等同类在研产品产生积极影响——这些药物均采用与 Skyrizi 相似的作用机制，有望抵消 2025 年已上市的 Stelara 生物类似药带来的市场冲击。

Meanwhile, on the commercial side, AbbVie’s experience in IBD, prominent physician outreach, and marketing teams will ensure Skyrizi’s success. As stated at the J. P. Healthcare Morgan conference 2025,  the company plans to aggressively back Rinvoq and Skyrizi in the IBD market to generate revenue lost due to Humira’s patent loss and subsequent biosimilar erosion. AbbVie's CEO, Rob Michael stated that both Skyrizi and Rinvoq are showing tremendous momentum in IBD, with strong capture rates in Crohn's and UC. The company sees IL-23s as a growing category and feels confident about its position with Skyrizi but also addressed Johnson & Johnson’s Tremfya as a strong competitor while being optimistic about Skyrizi's more substantial portfolio.
与此同时，在商业层面，艾伯维在炎症性肠病（IBD）领域的经验、突出的内科医生推广以及营销团队将确保 Skyrizi 的成功。正如 2025 年摩根大通医疗健康大会上所述，该公司计划在 IBD 市场大力支持 Rinvoq 和 Skyrizi，以弥补因修美乐专利到期及后续生物类似药冲击导致的收入损失。艾伯维首席执行官罗伯·迈克尔表示，Skyrizi 和 Rinvoq 在 IBD 领域均展现出强劲势头，在克罗恩病和溃疡性结肠炎治疗中占据显著市场份额。公司将 IL-23 抑制剂视为增长型品类，对 Skyrizi 的市场地位充满信心，但同时也承认强生公司的 Tremfya 是强劲竞争对手，不过对 Skyrizi 更丰富的投资组合持乐观态度。

“But the SEQUENCE study suggests that risankizumab may be better for certain endpoints, and now the GALAXI 2 suggests that maybe guselkumab is in some ways maybe a little bit better. And then for mirikizumab there was no difference. So, at least some of the anti-IL-23s might be slightly superior in efficacy to ustekinumab.” – US key opinion leader
"但 SEQUENCE 研究显示，risankizumab 可能对某些终点指标更优，而 GALAXI 2 研究则表明 guselkumab 在某些方面或许略胜一筹。至于 mirikizumab 则未显现差异。因此，至少部分抗 IL-23 药物在疗效上可能比 ustekinumab 稍具优势。"——美国关键意见领袖

“Other patients like the idea that with Skyrizi, you get three induction doses, not just one, and maybe that explains why the SEQUENCE trial was positive, maybe you’re just getting more drug, and it may not be intrinsic to the mechanism of action, it may just be that you’re getting more drug with the Skyrizi. But in any case, I tend to think of them similarly, but I’m open-minded to the idea that risankizumab might be a bit better, and I have to look at the SEQUENCE trial results in more detail.” – US key opinion leader
“其他患者喜欢 Skyrizi 的一点是，它能提供三次诱导剂量，而不仅仅是一次，这或许解释了为什么 SEQUENCE 试验结果呈阳性——可能只是因为患者获得了更多药物，而非其作用机制本身更优越。但无论如何，我倾向于认为它们效果相似，不过我也持开放态度，认为 risankizumab 可能略胜一筹，我需要更详细地研究 SEQUENCE 试验的结果。”——美国关键意见领袖

Eli Lilly’s Omvoh (mirikizumab) is the latest addition to the CD treatment armamentarium having gained approval by the FDA in January 2025. The drug has positioned itself among the most clinically promising products as it has performed well at both Phase II and Phase III trials and is being positioned to address unmet needs by targeting inadequate responders to biologic and conventional therapies. In the double-blind Phase III VIVID-1 trial, Omvoh demonstrated non-inferiority against Stelara for clinical remission, but failed to achieve superiority on endoscopic response even with a numerically higher result. In contrast, Skyrizi demonstrated non-inferiority for clinical remission and achieved superiority on endoscopic remission in the open-label Phase III SEQUENCE trial against Stelara. This places Omvoh at a disadvantage both clinically and commercially as Skyrizi is backed by AbbVie which is immensely strong in the IBD sector. Additionally, the market is becoming increasingly competitive with multiple Stelara biosimilars already launched and Johnson & Johnson’s Tremfya expected to gain approval in 2025.
礼来公司的 Omvoh（米利珠单抗）是克罗恩病治疗领域的最新成员，已于 2025 年 1 月获得美国食品药品监督管理局批准。该药物在 II 期和 III 期临床试验中均表现优异，旨在解决对生物制剂和传统疗法反应不足患者的未满足需求，因此被定位为最具临床前景的产品之一。在双盲 III 期 VIVID-1 试验中，Omvoh 在临床缓解方面证明了与 Stelara 的非劣效性，但即使数值更高，在内镜应答方面也未能实现优效性。相比之下，Skyrizi 在开放标签 III 期 SEQUENCE 试验中不仅证明了与 Stelara 在临床缓解方面的非劣效性，还实现了内镜缓解的优效性。由于 Skyrizi 背后有在炎症性肠病领域实力雄厚的艾伯维支持，这使得 Omvoh 在临床和商业上都处于劣势。此外，随着多个 Stelara 生物类似药已上市，以及强生公司的 Tremfya 预计将于 2025 年获批，市场竞争正变得越来越激烈。

Eli Lilly noted that Omvoh has gained first-line biologic coverage from two of the three largest pharmacy benefit managers in the US. This could provide a much needed boost for Omvoh, by directly challenging Skyrizi (which already has favorable formulary positioning) as both products will be placed in the preferred specialty tier and do not require failure of other biologics prior to use.
礼来公司指出，奥伏已在全美三大药房福利管理机构中的两家获得一线生物制剂承保资格。这将为奥伏提供亟需的市场助力——通过与已具备优势处方地位的喜开瑞直接竞争（两款药物均被列入优先专科用药层级且无需经历其他生物制剂治疗失败即可使用）。

“I mean, simplistically, when it first comes out, mirikizumab is going to be the UC drug, and risankizumab is going to be the Crohn's. But that's more due to the approval process than the efficacy.” – US key opinion leader
"简单来说，米利珠单抗上市初期将主攻溃疡性结肠炎适应症，而瑞莎珠单抗则专注克罗恩病。但这更多是审批流程所致，与疗效无关。"——美国关键意见领袖

“I think that mirikizumab is going to make quite a splash, what’s interesting is that while it’s approved for ulcerative colitis, the initial studies by Lilly showed that the NNT – the number needed to treat – was actually a little bit better for Crohn’s disease than for ulcerative colitis” – US key opinion leader
"我认为米利珠单抗将引发巨大反响。有趣的是，虽然它获批用于溃疡性结肠炎，但礼来初期研究显示，其治疗克罗恩病的 NNT（需治疗病例数）指标实际上略优于溃疡性结肠炎。"——美国关键意见领袖

Currently in the BLA state, Tremfya (guselkumab) has produced strong efficacy data in inadequate responders from the GALAXI Phase II/III trial and is positioned as a clinically attractive pipeline agent alongside other selective IL-23s. Johnson & Johnson released top-line results from the GALAXI 2 and 3 Phase III trials earlier in 2024. Both subcutaneous doses of 200mg every four weeks and 100mg every eight weeks showed superiority versus both placebo and ustekinumab, sparking anticipation for Tremfya's potential impact on the market. The data revealed impressive results in the endoscopic endpoints, with Tremfya showcasing superiority over ustekinumab. Updated results released later in 2024 found statistically significant better endoscopic response and remission rates compared to Stelara at week 48 in patients receiving both doses of Tremfya. Clinical remission rates were numerically superior in the Tremfya groups, but were not statistically significant compared to Stelara arm. Although Tremfya was unable to demonstrate superiority in clinical remission endpoints, on a combined endpoint of clinical remission and endoscopic response, the 200mg monthly dose produced a statistically significant superior response to ustekinumab.
目前处于生物制剂许可申请（BLA）阶段的特诺雅（古塞库单抗）在 GALAXI II/III 期试验中对治疗应答不足的患者展现出强劲疗效数据，与其他选择性 IL-23 抑制剂共同构成具有临床吸引力的在研药物梯队。强生公司在 2024 年初公布了 GALAXI 2 和 3 两项 III 期试验的顶线结果——无论是每四周 200 毫克还是每八周 100 毫克的皮下注射剂量，均显示出优于安慰剂和乌司奴单抗的疗效，引发市场对特诺雅潜在影响力的期待。数据显示该药物在内镜终点指标上表现亮眼，疗效显著优于乌司奴单抗。2024 年下半年公布的更新结果显示，接受两种剂量特诺雅治疗的患者在第 48 周时，其内镜应答率和缓解率相较喜达诺组均具有统计学显著优势。虽然特诺雅组的临床缓解率数值上更高，但与喜达诺组相比未达到统计学显著性差异。 尽管 Tremfya 未能在临床缓解终点上展现优势，但在临床缓解与内镜应答的复合终点指标上，每月 200mg 剂量组对比乌司奴单抗显示出统计学意义上的显著优效性。

Unlike the induction phase results from Eli Lilly’s SERENITY study, in which Omvoh’s endoscopic response rates were 26%, 38%, and 44% on low, mid, and high doses, respectively, Tremfya’s endoscopic response rates did not follow a dose response (36%, 40%, and 36% on low, mid, and high doses, respectively). Both SERENITY and GALAXI used the newer Simple Endoscopic Score for CD (SES-CD) measure to evaluate endoscopic response, which was developed as an alternative to the Crohn's Disease Endoscopic Index of Severity (CDEIS) that was used in AbbVie’s Phase II study of Skyrizi. Besides the lack of a dose response, it is also unfortunate that only the high dose of Tremfya achieved endoscopic remission, defined as an SES-CD score of two or less. In contrast to the disappointing endoscopic remission results, Tremfya achieved placebo-adjusted clinical remission rate of 38% for the 200mg dose. The GALAXI study also included a Stelara reference arm, revealing that Tremfya’s remission rates were numerically better than this comparator.
与礼来 SERENITY 研究诱导期结果不同（奥马珠单抗在低、中、高剂量组的内镜应答率分别为 26%、38%和 44%），特诺雅未呈现剂量依赖性应答（低、中、高剂量组内镜应答率分别为 36%、40%和 36%）。SERENITY 与 GALAXI 研究均采用新型简化克罗恩病内镜评分（SES-CD）评估内镜应答，该指标旨在替代艾伯维 Skyrizi 二期研究中使用的克罗恩病内镜下严重程度指数（CDEIS）。除缺乏剂量反应外，更遗憾的是仅高剂量特诺雅达到内镜缓解（定义为 SES-CD 评分≤2）。与令人失望的内镜缓解结果形成对比的是，特诺雅 200mg 剂量组的安慰剂校正临床缓解率达 38%。GALAXI 研究还设置了喜达诺参照组，数据显示特诺雅的缓解率数值上优于该对照药物。

Tremfya is already launched for plaque psoriasis and is positioned to become the fourth-to-market drug in its class to treat CD. Johnson & Johnson has extensive experience in the IBD field through Stelara and will be confident in its strategy to promote Tremfya. However, these are big shoes to fill as Stelara generated revenues of over $10 billion in 2024. With biosimilar erosion already affecting Stelara figures, Johnson & Johnson will lean heavily on Tremfya to recover lost revenue. The company, having gained an approval in UC in September 2024, has filed for regulatory submission for Tremfya in the EU, Japan and the US for Crohn's disease in mid-2024, with an FDA regulatory decision anticipated in April this year.
Tremfya 已获批用于治疗斑块状银屑病，并有望成为同类药物中第四个上市治疗克罗恩病的产品。强生公司通过 Stelara 在炎症性肠病领域积累了丰富经验，对其推广 Tremfya 的战略充满信心。然而 Stelara 在 2024 年创造了超过 100 亿美元的营收，要填补这个空缺并非易事。随着生物类似药侵蚀已开始影响 Stelara 的业绩数据，强生将主要依靠 Tremfya 来挽回流失的收入。该公司于 2024 年 9 月获得溃疡性结肠炎适应症批准后，已于 2024 年年中向欧盟、日本和美国监管机构提交了 Tremfya 治疗克罗恩病的上市申请，预计美国食品药品监督管理局将于今年四月做出监管决定。

“So, the problem is that when you look at the clinical trials, the efficacy of mirikizumab looks quite similar to risankizumab. So, I would say as far as efficacy is concerned, it’s approximately the same. The safety is similar, but the convenience of risankizumab is better with this On-Body Injector. A big question is, from what I have seen from the clinical trial data, it looks like the third one, meaning guselkumab, may be a little bit more effective.” – US key opinion leader
“因此，问题在于当你查看临床试验数据时，mirikizumab 的疗效看起来与 risankizumab 非常相似。就疗效而言，我认为两者大致相当。安全性方面也相近，但 risankizumab 配备的这款随身注射器使用更为便捷。根据我看到的临床试验数据，一个关键问题是第三款药物 guselkumab 似乎可能略胜一筹。”——美国关键意见领袖

Non-biologic DMARDs  非生物制剂 DMARDs

JAK inhibitors  JAK 抑制剂

JAK inhibitor Rinvoq (upadacitinib) is commercially promising as both a first-in-class product and a novel oral drug in CD. Rinvoq is already approved for many autoimmune indications, including UC. Targeting global markets broadens the drug’s commercial potential, and it has gained approval in the EU, Japan and US. Notably, AbbVie has extensive commercial resources and marketing experience with Humira, and is positioning Rinvoq as its next-generation product since Humira is now facing biosimilar competition in the US.
JAK 抑制剂 Rinvoq（乌帕替尼）作为克罗恩病领域首个同类产品及新型口服药物具有显著商业前景。该药已获批用于包括溃疡性结肠炎在内的多种自身免疫适应症，在欧盟、日本和美国获得上市许可更拓展了其全球商业潜力。值得注意的是，艾伯维凭借修美乐积累了丰富的商业资源和营销经验，现正将 Rinvoq 定位为接棒产品——因修美乐当前在美国正面临生物类似药竞争。

Published results from the U-EXCEED and U-EXCEL induction trials showcased 12-week clinical remission over placebo of 18% and 20%, respectively, and the U-ENDURE maintenance trial showed ~30% higher clinical remission over placebo at one year.
U-EXCEED 和 U-EXCEL 诱导试验公布的 12 周临床缓解率分别比安慰剂组高出 18%和 20%，而 U-ENDURE 维持试验显示一年后临床缓解率较安慰剂组提高约 30%。

In early September 2021, the FDA announced that there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with certain JAK inhibitors. Based on a large post-marketing safety study evaluating Xeljanz against TNF blockers in patients with RA, the FDA required a more alarming warning in the label for Xeljanz, with a downstream effect on the more selective JAK1 inhibitor Rinvoq. Apart from the safety issues, JAK inhibitors are also limited to patients who have not responded to or cannot tolerate one or more TNF blockers for currently labeled indications, which eliminated the ability for JAK inhibitors to be used in the first-line setting.
2021 年 9 月初，食品药品监督管理局宣布某些 JAK 抑制剂会增加严重心脏相关事件（如心脏病发作或中风）、癌症、血栓和死亡风险。基于一项针对类风湿关节炎患者的大型上市后安全性研究（比较 Xeljanz 与 TNF 阻滞剂），食品药品监督管理局要求在 Xeljanz 药品标签上添加更严厉的警示，这种监管影响也波及选择性更高的 JAK1 抑制剂 Rinvoq。除安全性问题外，JAK 抑制剂目前获批的适应症还限定于对一种或多种 TNF 阻滞剂无应答或不耐受的患者，这使其无法用于一线治疗。

In November 2022, the EMA also adopted measures to minimize the risk of serious side effects with JAK inhibitors. The recommendation stated that all JAK inhibitors should only be used if no suitable options are available in high-risk patients (patients aged over 65 years, those at a higher risk of major cardiovascular events, and smokers or long-time ex-smokers), pushing JAK inhibitors to later lines of therapy. The committee also recommended JAK inhibitors be used with caution in patients with risk factors for blood clots, and the lowest dosage be used in patient groups at risk of venous thromboembolism.
2022 年 11 月，欧洲药品管理局（EMA）还采取了措施以降低 JAK 抑制剂引发严重副作用的风险。该建议指出，对于高风险患者（65 岁以上老年人、主要心血管事件高风险人群、吸烟者或长期戒烟者），仅当无其他合适选择时方可使用 JAK 抑制剂，这将 JAK 抑制剂推后至更晚的治疗线使用。委员会还建议对有血栓风险因素的患者谨慎使用 JAK 抑制剂，并对静脉血栓栓塞风险患者群体采用最低剂量。

In mid-2023, the UK’s NICE provided positive guidance on Rinvoq, with the drug recommended for the treatment of moderate-to-severe CD if patients are non-responders, intolerant to previous biologic treatment, or contraindicated to TNF inhibitors. The recommendation was based on a cost-comparison study which placed Rinvoq as having a similar or lower cost than vedolizumab and ustekinumab.
2023 年年中，英国国家健康与临床卓越研究所（NICE）对 Rinvoq 给出了积极指导建议，推荐该药用于治疗对既往生物制剂治疗无应答、不耐受或存在 TNF 抑制剂禁忌症的中重度克罗恩病患者。此项建议基于一项成本对比研究，该研究表明 Rinvoq 的成本与维多珠单抗和乌司奴单抗相当或更低。

“Rinvoq, which is a selective JAK inhibitor, we tend to restrict its use to younger and healthier people, but again it’s an agent that I’m very excited about. As I mentioned earlier, I think combination therapy will be something to be very excited about. So, I think the JAK inhibitors will be drugs that will be used to induce remission, and then other drugs to keep people in remission.” – US key opinion leader
"Rinvoq 作为一种选择性 JAK 抑制剂，我们倾向于将其用于更年轻健康的患者群体，但这确实是一款令我非常振奋的药物。正如我之前提到的，联合疗法将带来令人期待的突破。我认为 JAK 抑制剂将成为诱导缓解的药物，而其他药物则用于维持缓解状态。"——美国关键意见领袖

Although the JAK inhibitors are plagued by black box warnings, physicians in the gastrointestinal community have opined that the adverse events seen are much more pronounced in the RA population. On the other hand, the IBD patient population is younger and less prone to cardiovascular events, and this has improved physician confidence in prescribing JAK inhibitors in CD.
尽管 JAK 抑制剂受到黑框警告的困扰，但消化内科医生们认为，这些不良反应在类风湿关节炎患者群体中表现得更为显著。相比之下，炎症性肠病患者群体更年轻且心血管事件发生率更低，这增强了内科医生在克罗恩病中处方 JAK 抑制剂的信心。

S1P receptor modulators  S1P 受体调节剂

Bristol Myers Squibb's entry into the CD market has hit a major setback as its only pipeline candidate in the indication, Zeposia (ozanimod), showed disappointing results in the initial analysis of the first of two induction studies in the Phase III YELLOWSTONE trial. The trial failed to achieve the primary endpoint of clinical remission at week 12. The drug had only managed to show moderate efficacy in the open-label Phase II trial, which enrolled a paltry 69 subjects, and the most common serious adverse events in ≥2 patients were CD flare, fistulizing disease, intestinal obstruction, and abdominal abscess. Zeposia required more robust data in the Phase III trials for its novel mechanism of action and convenient oral administration method to be advantageous, but the results from YELLOWSTONE have put a significant dent in the future of the drug in this indication. Following the disappointing results, the company terminated the Phase III maintenance trial and an induction trial (Phase III - YELLOWSTONE (3201)).
百时美施贵宝在克罗恩病领域的布局遭遇重大挫折，其唯一管线候选药物 Zeposia（奥扎莫德）在 III 期 YELLOWSTONE 试验的两项诱导研究首次分析中表现令人失望。该试验未能达到第 12 周临床缓解的主要终点。这款药物在仅纳入 69 名受试者的开放标签 II 期试验中仅显示出中等疗效，且≥2 例患者中最常见的严重不良事件包括克罗恩病急性发作、瘘管形成、肠梗阻和腹腔脓肿。Zeposia 本需在 III 期试验中获得更有力的数据，才能使其新颖的作用机制和便捷的口服给药方式显现优势，但 YELLOWSTONE 试验结果严重影响了该药物在此适应症中的前景。基于令人失望的结果，该公司已终止 III 期维持试验和一项诱导试验（III 期-YELLOWSTONE（3201））。

“For maintaining a remission though, an anti-interleukin may be even better, and the best drug right now, although it’s not yet approved, I think in Crohn’s, might actually be an S1P, because consider the mechanism of action, it keeps the lymphocytes locked up in their barracks.” – US key opinion leader
"不过，要维持缓解状态，抗白细胞介素药物可能效果更佳。目前最有效的药物——虽然尚未获批——我认为在克罗恩病治疗中可能当属 S1P 受体调节剂，因为从作用机制来看，它能将淋巴细胞'关在兵营里'。"——美国权威专家

Pipeline drug Velsipity (etrasimod) is another prospect for the CD market as an S1P receptor modulator. The drug recently gained approval in UC and offers convenience as an oral therapy while demonstrating favorable tolerability and safety data in clinical trials in UC, where it did not require any dose titration and exhibited minimal lowering of heart rate, unlike Zeposia. Results from the Phase II/III - CULTIVATE trial Substudy A (Phase II dose ranging trial) showed 23.1% and 33.3% of patients who responded to the induction phase and were treated with 2mg and 3mg etrasimod in the extension period achieved the primary endpoint of endoscopic response. However, safety was a concern as the trial demonstrated a high rate of treatment emergent adverse events (TEAEs), with 79% and 89% of patients experiencing TEAEs in the 2mg and 3mg arms, respectively.  Considering that no S1P receptor modulators have successfully completed Phase III, Velsipity has a steep road ahead. On the commercial aspect, Pfizer’s acquisition of Arena Pharmaceuticals and partnering with Everest Medicines will extend the drug’s commercial resources and marketing experience.
管线药物 Velsipity（etrasimod）作为 S1P 受体调节剂，是克罗恩病市场的另一潜力产品。该药近期获批用于溃疡性结肠炎治疗，作为口服疗法使用便捷，且在溃疡性结肠炎临床试验中展现出良好的耐受性和安全性——不同于 Zeposia，它无需剂量滴定且对心率的降低作用极小。II/III 期 CULTIVATE 试验子研究 A（II 期剂量探索试验）结果显示，在诱导期有应答的患者中，分别有 23.1%和 33.3%接受 2mg 与 3mg etrasimod 延长治疗的患者达到了内镜应答的主要终点。但安全性问题值得关注，试验中治疗 emergent 不良事件（TEAEs）发生率较高，2mg 组和 3mg 组分别有 79%和 89%患者出现 TEAEs。考虑到目前尚无 S1P 受体调节剂成功完成 III 期试验，Velsipity 面临严峻挑战。商业层面，辉瑞收购 Arena 制药并与 Everest Medicines 合作，将增强该药物的商业资源和营销经验。

Stem cell therapy  干细胞疗法

Adult allogeneic expanded adipose-derived stem cells
成人异体扩增脂肪源性干细胞

Alofisel was a novel therapy approved in 2018 in the EU based on the ADMIRE-CD (EU) study. The treatment was reserved for the most refractory cases of CD with complex perianal fistulas, thus addressing an unmet need since as many as 50% of CD patients developed fistulas within a 20-year timespan. As the therapy did not treat the underlying disease, Alofisel’s use was restricted to severe fistula cases, dampening its commercial potential. In October 2023, following disappointing data from the Phase III ADMIRE-CD-II trial, where Alofisel did not achieve the primary endpoint of combined remission at week 24, drug development was discontinued in the US. This study was also assessed by the CAT (EMA’s committee for advanced therapies) with the drug failing to demonstrate better effectiveness compared to placebo for treating complex anal fistulas in adults with CD. As Takeda failed to provide data supporting its efficacy for treating fistulas, the company withdrew from the European market in late 2024.
Alofisel 是一种基于 ADMIRE-CD（欧盟）研究于 2018 年在欧盟获批的新型疗法。该治疗专门针对伴有复杂肛周瘘管的最难治性克罗恩病病例，满足了未满足的医疗需求——约 50%的克罗恩病患者在 20 年内会出现瘘管。由于该疗法不能治疗基础疾病，Alofisel 的使用仅限于严重瘘管病例，这限制了其商业潜力。2023 年 10 月，在 III 期 ADMIRE-CD-II 试验中，Alofisel 未能达到第 24 周联合缓解的主要终点，随后美国停止了该药物的开发。欧洲药品管理局先进疗法委员会（CAT）评估也显示，该药治疗成人克罗恩病复杂肛瘘的疗效未能优于安慰剂。由于武田制药未能提供支持其治疗瘘管疗效的数据，该公司于 2024 年底退出欧洲市场。

“It [Alofisel] had a negative trial in the US, so it’s game over. This is not an effective treatment. It was used [in the EU and Japan], but now doctors are starting to use it less and less.” – EU key opinion leader
“它[Alofisel]在美国的临床试验结果不佳，所以游戏结束了。这不是一种有效的治疗。虽然它曾在[欧盟和日本]使用，但现在医生们开始越来越少地使用它。”——欧盟关键意见领袖

Antibiotics  抗生素

Combination antibiotics  联合抗生素

RHB-104 is a single-capsule combination of 95mg clarithromycin, 45mg rifabutin, and 10mg clofazimine for the treatment of Mycobacterium avium subspecies paratuberculosis (MAP) infection, which has been implicated as a disease-promoting factor in CD. RHB-104 is attractive as an oral therapy and is differentiated by its novelty, considering that other marketed drugs are immunosuppressants as opposed to addressing the suspected cause of the disease. Although it is being positioned as an add-on to conventional therapies and Humira/Remicade, it is likely to be an affordable addition and may secure early positioning in the treatment algorithm. Although trial data have demonstrated the drug to be safe and well tolerated, in the Phase III MAP US trial, the statistical significance demonstrated on the remission endpoints at week 16 and week 26 was not achieved at week 52. Moreover, the drug’s use may be limited by the problem of antibiotic resistance, and success is contingent upon the uncertain development of a MAP diagnostic in collaboration with several US universities and laboratories. A diagnostic test for MAP is critical for RHB-104’s development pathway and is being pursued before initiating a second Phase III trial. Additionally, RedHill Biopharma would benefit from a strategic partnership to pool commercial resources and marketing capabilities.
RHB-104 是一种单胶囊组合制剂，含有 95 毫克克拉霉素、45 毫克利福布汀和 10 毫克氯法齐明，用于治疗鸟分枝杆菌副结核亚种（MAP）感染，该感染已被认为是克罗恩病（CD）的促发因素。作为一种口服疗法，RHB-104 因其创新性而独具吸引力，因为目前市售的其他药物均为免疫抑制剂，而非针对该疾病的疑似病因。尽管该药物被定位为传统疗法及 Humira/Remicade 的辅助用药，但其价格可能较为亲民，并有望在治疗算法中占据早期地位。虽然试验数据表明该药物安全且耐受性良好，但在 MAP 美国 III 期试验中，第 16 周和第 26 周缓解终点的统计学显著性未能在第 52 周得以维持。此外，该药物的应用可能受限于抗生素耐药性问题，其成功与否还取决于与美国多所大学及实验室合作开发 MAP 诊断方法的不确定性进展。 针对 MAP 的诊断检测对 RHB-104 的研发路径至关重要，该公司将在启动第三阶段二期试验前完成此项工作。此外，RedHill Biopharma 若能建立战略合作伙伴关系，整合商业资源与营销能力，将大有裨益。

“Yes, this drug feels like it’s been around for over 10 years, and they’ve struggled to even enroll patients in their trials. It has just bounced around. Maybe there are patients with mild bio-naïve Crohn’s disease where you might want to consider this, but first we just have to see robust data, and we haven’t seen robust data yet. You’ll get me going here, but I feel like it’s driven by people who are frankly zealots about this mycobacterium paratuberculosis hypothesis, and so, yes, that’s all I can say.” – US key opinion leader
"没错，这款药物感觉已经存在十多年了，他们甚至在招募试验患者方面都举步维艰。它就像个皮球被踢来踢去。或许对于那些轻度未接受过生物制剂治疗的克罗恩病患者，你会考虑使用它，但首先我们必须看到可靠的数据——而目前我们还没看到。恕我直言，我感觉推动这件事的人完全就是副结核分枝杆菌假说的狂热信徒，所以，是的，这就是我的全部看法。"——美国关键意见领袖

“If you manipulate the microbiota by applying antibiotics, and thereby changing the composition, of course people will get temporarily better, and in fistulizing disease in particular this can be a very helpful add-on to any kind of targeted therapy. But I don’t think it’s a long-standing concept that we should pursue.” – US key opinion leader
"如果通过使用抗生素来调控微生物群，从而改变其组成，患者当然会暂时好转——特别是对于瘘管型疾病，这可以作为任何靶向治疗的有效辅助手段。但我不认为这是个值得长期追求的治疗理念。"——美国关键意见领袖

Increasing interest in combination therapies
联合疗法正受到越来越多的关注

Despite the increasing availability of therapies and novel launches, achieving the therapeutic goals mentioned in the STRIDE-II guidelines remain challenging. The STRIDE-II (Selecting Therapeutic Targets in Inflammatory Bowel Disease) initiative identified clinical remission and endoscopic response as the most important short term treatment goals in CD and also included transmural healing as a newly recognized adjunctive measure for treatment outcome. Considering the complex pathology of IBD, many companies are following the scientific community in researching combination regimens using advanced therapies. Combination therapies using conventional drugs and advanced targeted therapies have been found to be beneficial in IBD and lay the foundation for advanced combination therapies. Very few trials are looking at combination therapies and much of the data is from retrospective trails. However, there has been increased interest in pharmaceutical companies to pursue combination therapies enrolling novel therapies, as well as established therapies, in an effort to extended lifecycle management. Johnson & Johnson has initiated the DUET-CD trial, which has enrolled over 700 patients and will analyze combination therapy with guselkumab and golimumab. Takeda, along with Royalty Pharma and Roche, has initiated a Phase IIIb trial combining intravenous vedolizumab and oral upadacitinib compared to intravenous vedolizumab monotherapy in CD.
尽管疗法和新药上市日益增多，但实现 STRIDE-II 指南中提出的治疗目标仍具挑战性。STRIDE-II（炎症性肠病治疗目标选择）倡议将临床缓解和内镜应答列为克罗恩病最重要的短期治疗目标，同时将透壁愈合作为治疗结果新认可的辅助指标。考虑到 IBD 复杂的病理机制，许多企业正追随科学界的步伐，研究采用先进疗法的联合治疗方案。传统药物与先进靶向疗法相结合的联合治疗已被证实对 IBD 有益，并为高级联合疗法奠定基础。目前关注联合疗法的临床试验极少，多数数据来自回顾性研究。然而，制药公司对采用新疗法与成熟疗法相结合的联合治疗方案兴趣渐增，以期延长产品生命周期管理。 强生公司已启动 DUET-CD 试验，该试验招募了 700 多名患者，将分析古塞库单抗与戈利木单抗的联合治疗方案。武田制药联合 Royalty Pharma 和罗氏公司开展了一项 IIIb 期试验，比较静脉注射维多珠单抗联合口服乌帕替尼与单用静脉注射维多珠单抗治疗克罗恩病的效果。

Despite formulary constraints, novel pipeline drugs will expand the market
尽管存在医保目录限制，新型在研药物仍将推动市场扩张

The entry of novel drug classes will drive expansion of the CD market, despite facing cost-related barriers to uptake. The pipeline holds distinct prospects that aim to treat non-responders. These will be welcomed for their distinguished mechanisms of action, and the oral therapies will further offer additional convenience in the CD treatment algorithm. On the other hand, newer premium-priced entrants will likely be relegated to later lines of therapy after cheaper conventional drugs and biosimilars.
新型药物类别的进入将推动克罗恩病市场发展，尽管面临成本相关的使用障碍。在研管线药物针对治疗无应答患者展现出独特前景，这些药物因其独特的作用机制将受到欢迎，而口服疗法还将为克罗恩病治疗算法提供更多便利。另一方面，定价较高的新型药物可能会被安排在更靠后的治疗线序，在价格更低的传统药物和生物类似药之后使用。

Anti TL1As have sparked interest among KOLs. TL1A and its target receptors are implicated in fibrosis and act as powerful co-stimulators of immunological responses with enhanced specificity for mucosal tissues. TL1A binds to two target receptors, DR3 and DcR3. The former is involved in pro-inflammatory signaling, while the latter maintains natural homeostasis. Although anti-TL1As are being investigated in UC, this is a relatively newer mechanism in CD. The two front runners utilizing this mechanism of action are Teva’s Duvakitug and Merck’s MK-7240, both of which have completed a Phase II trial in CD.
抗 TL1A 药物已引起关键意见领袖的关注。TL1A 及其靶向受体与纤维化进程相关，并能作为免疫反应的强力共刺激因子，对黏膜组织具有增强的特异性。TL1A 可与两个靶向受体结合——DR3 和 DcR3：前者参与促炎信号传导，后者则维持天然稳态。虽然抗 TL1A 药物正在溃疡性结肠炎(UC)领域开展研究，但在克罗恩病(CD)中仍属较新的作用机制。采用该机制的两款领跑药物分别是梯瓦的 Duvakitug 和默克的 MK-7240，二者均已完成针对 CD 的 II 期临床试验。

Biosimilar erosion of key brands will intensify over the next 10 years 
未来十年内，核心品牌药将面临生物类似药更猛烈的市场侵蚀

Over the next decade, all key marketed brands for CD will face patent expiry. The European market has taken the brunt of biosimilar erosion, with earlier launches and greater acceptance compared to other countries. In the US, biosimilars will initially face challenges in usurping branded anti-TNFs due to substantial originator rebates and exclusive contracting with payers. Over time, biosimilar penetration is anticipated to gain more momentum as international real-world evidence accumulates and long-term data support biosimilar efficacy and safety.
未来十年，所有已上市的关键 CD 治疗品牌药都将面临专利到期。欧洲市场首当其冲受到生物类似药冲击，与其他国家相比，其生物类似药上市更早且接受度更高。在美国，由于原研药提供大幅返利并与支付方签订独家合约，生物类似药在初期取代品牌抗 TNF 药物时将面临挑战。但随着国际真实世界证据的积累以及长期数据对生物类似药疗效和安全性的支持，预计生物类似药的市场渗透将获得更大动力。

Although biosimilar uptake in the US has been slow following biosimilar launch early in January 2023, formularies are now shifting to prefer adalimumab biosimilars. CVS Caremark recently announced the removal of Humira from its major commercial template formularies altogether, which should allow physicians and patients to grow their confidence and familiarity with biosimilars and encourage uptake. Furthermore, four Stelara biosimilars have already launched in the US and is competing for formulary access offering aggressive discounts to the originator.
尽管 2023 年 1 月初生物类似药在美国上市后推广缓慢，但目前各处方集已开始转向优先推荐阿达木单抗生物类似药。CVS Caremark 近期宣布将修美乐彻底移出其主要商业模板处方集，此举应有助于提升医生和患者对生物类似药的信心与熟悉度，从而促进使用。此外，已有四款乌司奴单抗生物类似药在美国上市，正通过向原研药发起激进折扣竞争处方集准入资格。

This is a snapshot of quotes from KOLs interviewed by our analysts. To view complete interviews, access KOL Insights.
以下是我们分析师采访的关键意见领袖(KOL)的言论摘要。如需查看完整访谈，请访问 KOL 见解栏目。

“I think one of the things that we don’t really have in IBD is we don’t have a lot of sequencing data. So something that would give us some idea of how these agents – and that applies for the new JAKs – work in people that have been exposed to TNFs or Entyvio or Stelara, just so we can get a better sense of whether it might work better before one or if it works better after. So any kind of sequencing information would be helpful, and then any sort of biomarker or any way to predict who might respond to that, to sort of inform our decision, would be very helpful too.” – US key opinion leader
“我认为我们在炎症性肠病领域真正缺乏的是大量序列数据。如果能获得一些信息，帮助我们了解这些药物——包括新型 JAK 抑制剂——在曾使用过 TNF 抑制剂、Entyvio 或 Stelara 的患者身上的作用机制，就能更清楚地判断它们是否在某种治疗顺序中效果更佳。任何序列信息都会很有帮助，此外任何生物标志物或预测患者反应的方法，能为我们的决策提供依据的信息也都极其重要。”——美国关键意见领袖

"Well, I think the main challenge for inflammatory bowel disease is still that although we have an increasing portfolio of novel treatment targets and compounds being approved, we're running into the challenge that we don't know what works best in first, second, and third line." – EU key opinion leader
“我认为炎症性肠病治疗面临的主要挑战在于：尽管新型治疗靶点和化合物获批的投资组合不断扩大，但我们仍面临一个难题——无法确定哪种方案在一线、二线和三线治疗中最有效。”——欧洲关键意见领袖

"The biggest challenge for the next decade for IBD treatment developers is to find a better compromise between efficacy and safety." – EU key opinion leader
“未来十年炎症性肠病治疗研发者面临的最大挑战，是在疗效与安全性之间找到更优的平衡点。”——欧洲关键意见领袖

“There needs to be a way to predict which biologic a patient will respond to without having to find out several months in that they are not responding. With regards to biologic options, there needs to more options with rapid onset of action (clinical remission as fast as four weeks) and with more histologic remission at the one-year mark (even in those who have previously tried and failed an anti-TNF).” – US physician
“必须找到一种方法，能在不耗费数月时间验证无效的情况下，提前预测患者对哪种生物制剂会产生反应。在生物制剂选择方面，需要更多能快速起效（最快四周实现临床缓解）且一年时点组织学缓解率更高（即使对曾使用抗 TNF 药物失败的患者也有效）的治疗方案。”——美国内科医生

“It would be very helpful to know which drug is most likely to lead to an excellent response and remission rate in an individual patient – personalized medicine. Biomarkers [that are] more drug-specific and individualized like CRP and fecal calprotectin may be the answer here, and several are in development.” – US physician
“若能知晓哪种药物最可能让个体患者获得极佳应答率和缓解率——即实现个性化医疗——将极具价值。像 CRP 和粪便钙卫蛋白这类更具药物特异性及个体化的生物标志物可能是解决方案，目前已有多个相关项目在研发中。”——美国内科医生

"In Crohn’s disease, we’re starting to see the comparison data, like with the SEQUENCE study, although it’s not fully published, so I always feel I have to take it with a grain of salt if I haven’t read the full paper. But the SEQUENCE study suggests that risankizumab may be better for certain endpoints, and now the GALAXI 2 suggests that maybe guselkumab is in some ways maybe a little bit better." – US key opinion leader
“在克罗恩病领域，我们开始看到比较性数据，比如 SEQUENCE 研究，虽然尚未完全发表，因此我总觉得在未阅读完整论文前需持保留态度。但 SEQUENCE 研究表明 risankizumab 可能对某些终点指标更优，而 GALAXI 2 研究则提示 guselkumab 在某些方面或许略胜一筹。”——美国关键意见领袖

“Yes, there’s maybe a few more unmet needs in Crohn’s than in ulcerative colitis. We have the same issue of having like a ceiling of efficacy in Crohn’s disease. We also have really no agent that works for mild Crohn’s disease, something that would change the course and change the long-term outcomes of that. So something that’s safe and can kind of keep someone completely right at the beginning with mild disease would be helpful.” – US key opinion leader
"确实，克罗恩病相比溃疡性结肠炎可能存在更多未满足的医疗需求。我们在克罗恩病治疗中同样面临疗效天花板的问题。目前还没有任何针对轻度克罗恩病的有效治疗手段——那种能够改变疾病进程、改善长期预后的药物。因此，如果能有一种安全可靠的治疗方案，让轻度患者在发病初期就得到完全控制，将会大有裨益。" ——美国关键意见领袖

“In my experience, Crohn’s disease is a bit more difficult to induce into remission and maintain in remission than ulcerative colitis. Hence, the unmet needs in the treatment of CD are greater than with ulcerative colitis.” – US physician
"根据我的临床经验，克罗恩病比溃疡性结肠炎更难诱导缓解并维持缓解状态。因此，克罗恩病在治疗领域存在的未满足需求比溃疡性结肠炎更为突出。" ——美国内科医生

“The ultimate unmet need is attaining the desired state of deep remission and the possibility of stopping therapy. Clearly more work needs to be done to decide which patients may reach this category, but research here is progressing by the treat-to-target approach to therapy. Hopefully, more agents with more safe and effective mechanisms of action will be developed to fit this ultimate unmet need.” – US physician
“最终未被满足的需求是实现深度缓解的理想状态及停止治疗的可能性。显然，需要更多工作来确定哪些患者能达到这一目标，但通过‘达标治疗’策略，相关研究正在取得进展。希望未来能研发出更多具有更安全有效作用机制的药物，来满足这一终极未竟之需。”——美国内科医生

“I believe that in the coming years, we are going to see the biologics largely replaced in their market share by the small molecules, the small fusion receptor proteins, or the JAKs. I’m pretty hot on the JAK inhibitors for their rapid action, and even some of the new drugs like vidofludimus. We’re starting to see clinical trial data helping for three years for maintenance.” – US key opinion leader
“我相信在未来几年，我们将看到生物制剂的市场份额很大程度上被小分子药物、小型融合受体蛋白或 JAK 抑制剂所取代。我非常看好 JAK 抑制剂的快速起效特性，甚至包括维度氟迪莫斯等新药。我们已开始看到维持治疗三年的临床试验数据支持。”——美国关键意见领袖

“As far as oral drugs, this is a relative unmet need (currently already being filled by tofacitinib in UC). JAK inhibitors as well as the novel mechanism of action drug ozanimod are all oral and will also provide additional options for those who want to avoid intravenous/subcutaneous routes.” – US physician
“就口服药物而言，这仍是相对未满足的临床需求（目前托法替布已在溃疡性结肠炎领域填补该空白）。JAK 抑制剂以及具有新型作用机制的奥扎莫德均为口服制剂，将为希望避免静脉/皮下给药途径的患者提供更多选择。”——美国内科医生

“Depending on how quickly it gets adopted, and as we gain our experience with Janus kinase inhibitors I think because they’re oral drugs, easy to administer, and patients like it, it will certainly increase its market share” – UK key opinion leader
“根据其临床应用推广速度，随着我们对 Janus 激酶抑制剂使用经验的积累——鉴于其口服给药便利性及患者接受度高——我认为其市场份额必将持续扩大。”——英国关键意见领袖

“And then, we don’t have anything that works on fibrosis in Crohn’s, so something that would help reduce or prevent stricture formation. And then the last thing would be, we don’t really have very good agents for fistulizing disease, so we need something a bit more for that… Maybe eventually about half [of patients have fibrosis]. There is some overlap there. Some of our fistulizing patients also get strictures as well.” – US key opinion leader
"其次，我们目前对克罗恩病纤维化束手无策，亟需能帮助减轻或预防狭窄形成的疗法。最后，针对瘘管型病变我们也缺乏非常有效的药物，这方面需要更多突破...可能最终约半数患者会出现纤维化。这两种情况存在交叉，部分瘘管患者同时也会发生肠道狭窄。" ——美国关键意见领袖

“The injection of stem cells for perianal fistula I think for sure has a good future. I mean they’ve used all kinds of other things, gels and jellies, fat, all kinds of stuff. So, stem cells look as good or better than anything else so far.” – US key opinion leader
"我认为干细胞注射治疗肛瘘肯定前景广阔。他们尝试过各种其他方法，凝胶、果冻状物质、脂肪组织等等。相比之下，干细胞疗法目前看来效果不逊于甚至优于其他所有方案。"——美国关键意见领袖

“So, the problem is that when you look at the clinical trials, the efficacy of mirikizumab looks quite similar to risankizumab. So, I would say as far as efficacy is concerned, it’s approximately the same. The safety is similar, but the convenience of risankizumab is better with this On-Body Injector.” – US key opinion leader
"问题在于，从临床试验数据来看，mirikizumab 的疗效与 risankizumab 非常接近。就疗效而言，我认为两者基本相当。安全性也相似，但 risankizumab 配备的 On-Body 注射器使用起来更为便捷。"——美国关键意见领袖

“There is no head-to-head comparison [of Skyrizi] with Stelara. So, it’s a slightly different molecule, but it works very well similarly to Stelara. So, I cannot compare it with ustekinumab because there isn’t a comparison which is published.” – UK key opinion leader
"[Skyrizi]与 Stelara 尚未进行头对头比较。虽然分子结构略有差异，但两者的作用机制非常相似。由于没有已发表的对照研究，我无法将其与优特克单抗进行直接比较。"——英国关键意见领袖

"Combination is something that is happening off-label, and in clinical practice it is much faster than waiting on reimbursement that is not yet available. So, a lot of doctors are using it because they feel that there is a special patient population, after they start failing a couple of mechanisms of action, that need something else today that is not addressed by the current options. So, that's why they start combining multiple drugs." – EU key opinion leader
"联合用药目前属于超说明书使用，但在临床实践中，这远比等待尚未获批的医保报销要快得多。许多医生之所以采用这种方法，是因为他们认为存在特定患者群体——当这些患者对几种作用机制相继失效后，当下就需要现有疗法无法满足的其他治疗方案。这就是他们开始联合使用多种药物的原因。"——欧盟关键意见领袖

There is a critical unmet need for predictive biomarkers
预测性生物标志物存在重大未满足需求

Physicians emphasize the need for predictive biomarkers that will facilitate the implementation of effective treatment regimens earlier. Currently, it may take months to establish a response and identify non-responders to treatment. Thus, a stratified medicine approach would have the potential to radically improve the efficiency of treatment and treatment outcomes. Approximately one-third of anti-TNF-naïve patients have a primary non-response to anti-TNF therapy, while a similar proportion are secondary non-responders (initial anti-TNF responders who lose their response or become intolerant).
临床医生强调亟需能促进早期实施有效治疗方案的预测性生物标志物。目前可能需要数月时间才能确定患者对治疗的反应并识别无应答者。因此，分层医疗方法有望从根本上提升治疗效率和治疗效果。约三分之一未使用过抗 TNF 药物的患者会出现原发性无应答，而类似比例的患者会产生继发性无应答（即最初对抗 TNF 药物有反应，但随后失去反应或出现不耐受）。

“I think one of the things that we don’t really have in IBD is we don’t have a lot of sequencing data. So, something that would give us some idea of how these agents – and that applies for the new JAKs – work in people that have been exposed to TNFs or Entyvio or Stelara, just so we can get a better sense of whether it might work better before one or if it works better after. So, any kind of sequencing information would be helpful, and then any sort of biomarker or any way to predict who might respond to that, to sort of inform our decision, would be very helpful too.” – US key opinion leader
“我认为我们在炎症性肠病（IBD）领域真正缺乏的是大量序列数据。这些数据能让我们了解这些药物——包括新型 JAK 抑制剂——在曾使用过 TNF 抑制剂、Entyvio 或 Stelara 的患者身上的作用机制，从而更清楚地判断某种药物是作为一线治疗更有效，还是作为后续治疗更有效。任何类型的序列信息都将大有裨益，此外，任何能预测患者治疗反应的生物标志物或方法，都能为我们的临床决策提供重要依据。”——美国关键意见领袖

“We don’t have that [predictive biomarkers], so this whole process of picking drugs is basically empiric, and it’s not really based on good evidence.” – US key opinion leader
“我们目前缺乏这种[预测性生物标志物]，因此整个药物选择过程基本上是经验性的，并非基于确凿证据。”——美国关键意见领袖

“The frustration with our whole field is that we don’t have predictive molecular biomarkers, like the oncologists have, so when we’re picking drugs it’s largely empiric, and it would be nice to have precision medicine where we could say, ah, you are going to respond to this class or you’re going to respond to that class.” – US key opinion leader
"我们整个领域令人沮丧的是，我们没有像肿瘤学家那样拥有预测性分子生物标志物，因此在选择药物时很大程度上是经验性的。如果能实现精准医疗，让我们能明确判断'这类药物对你有效'或'那类药物对你有效'，那将会非常理想。"——美国关键意见领袖

“There needs to be a way to predict which biologic a patient will respond to without having to find out several months in that they are not responding. With regards to biologic options, there needs to more options with rapid onset of action (clinical remission as fast as four weeks) and with more histologic remission at the one-year mark (even in those who have previously tried and failed an anti-TNF).” – US physician
“必须找到一种方法，能在不耗费数月时间验证无效的情况下，预测患者对哪种生物制剂会产生反应。就生物制剂选择而言，需要更多能快速起效（最快四周实现临床缓解）且一年时点达到更高组织学缓解率（包括对抗 TNF 药物既往治疗失败者）的选项。”——美国内科医生

“It would be very helpful to know which drug is most likely to lead to an excellent response and remission rate in an individual patient – personalized medicine. Biomarkers [that are] more drug-specific and individualized like CRP and fecal calprotectin may be the answer here, and several are in development.” – US physician
“若能知晓哪种药物最可能让特定患者获得极佳应答率和缓解率——即个性化医疗——将极具价值。像 C 反应蛋白和粪便钙卫蛋白这类更具药物特异性及个体化的生物标志物可能是解决方案，目前已有多个相关项目在研。”——美国内科医生

Effective biologics with rapid onset and sustained remission
快速起效且持续缓解的高效生物制剂

Physicians value earlier clinical remission, with a desire for drugs that achieve clinical remission by four weeks and histologic remission by one year. A KOL highlights the need for effective drugs to treat early disease:
医生们重视早期临床缓解，希望药物能在四周内实现临床缓解，并在一年内达到组织学缓解。一位关键意见领袖强调需要有效药物治疗早期疾病：

“Yes, there’s maybe a few more unmet needs in Crohn’s than in ulcerative colitis. We have the same issue of having like a ceiling of efficacy in Crohn’s disease. We also have really no agent that works for mild Crohn’s disease, something that would change the course and change the long-term outcomes of that. So something that’s safe and can kind of keep someone completely right at the beginning with mild disease would be helpful.” – US key opinion leader
"是的，克罗恩病可能比溃疡性结肠炎存在更多未满足的需求。我们在克罗恩病治疗中同样面临疗效天花板的问题。目前确实没有针对轻度克罗恩病的有效药物，那种能够改变病程、改善长期预后的药物。所以如果能有一种安全的药物，可以让轻度患者在疾病初期就完全保持健康状态，将会非常有帮助。"——美国关键意见领袖

“[...] the key driver of success of therapy, more in Crohn’s disease than in UC, but in Crohn’s disease, the key driver of success is early. If you catch the disease early enough, the chance that the patients will respond to the medication is much higher, and the chance that you will avoid the progression of the disease towards complications, the same, it’s much, much higher.” – US key opinion leader
"[...]治疗成功的关键驱动力——在克罗恩病中比在溃疡性结肠炎中更为明显——就是早期干预。如果能足够早地发现疾病，患者对药物产生反应的概率会高得多，避免疾病向并发症发展的机会也同样会大幅提升。"——美国关键意见领袖

“In my experience, Crohn’s disease is a bit more difficult to induce into remission and maintain in remission than ulcerative colitis. Hence, the unmet needs in the treatment of CD are greater than with ulcerative colitis.” – US physician
“根据我的经验，克罗恩病比溃疡性结肠炎更难诱导缓解并维持缓解状态。因此，克罗恩病治疗领域未被满足的需求比溃疡性结肠炎更为突出。”——美国内科医生

“The ultimate unmet need is attaining the desired state of deep remission and the possibility of stopping therapy. Clearly more work needs to be done to decide which patients may reach this category, but research here is progressing by the treat-to-target approach to therapy. Hopefully, more agents with more safe and effective mechanisms of action will be developed to fit this ultimate unmet need.” – US physician
“最根本的未满足需求是实现深度缓解的理想状态并有望终止治疗。虽然需要更多研究来确定哪些患者能达到这一目标，但通过'达标治疗'策略，相关研究正在取得进展。希望未来能开发出更多具有安全高效作用机制的新药来满足这一终极需求。”——美国内科医生

“I believe that in the coming years, we are going to see the biologics largely replaced in their market share by the small molecules, the small fusion receptor proteins, or the JAKs. I’m pretty hot on the JAK inhibitors for their rapid action, and even some of the new drugs like vidofludimus. We’re starting to see clinical trial data helping for three years for maintenance.” – US key opinion leader
“我认为未来几年，生物制剂的市场份额将主要被小分子药物、小型融合受体蛋白或 JAK 抑制剂取代。我特别看好 JAK 抑制剂的快速起效特性，包括维氟鲁米司等新型药物。现有临床试验数据显示其维持治疗效果可达三年。”——美国关键意见领袖

Novel oral treatments  新型口服疗法

Physicians voice the need for an expansion of the market to include more oral options that will provide flexibility and convenience for those who have difficulties with injectables.
医生们表达了扩大市场的需求，希望增加更多口服药物选择，为那些难以接受注射治疗的患者提供灵活性和便利性。

“As far as oral drugs, this is a relative unmet need (currently already being filled by tofacitinib in UC). JAK inhibitors as well as the novel mechanism of action drug ozanimod are all oral and will also provide additional options for those who want to avoid intravenous/subcutaneous routes.” – US physician
"就口服药物而言，这仍是一个相对未被满足的需求（目前溃疡性结肠炎领域已由托法替尼填补）。JAK 抑制剂以及具有新型作用机制的奥扎莫德都是口服制剂，将为希望避免静脉/皮下给药途径的患者提供更多选择。"——美国内科医生

“Depending on how quickly it gets adopted, and as we gain our experience with Janus kinase inhibitors I think because they’re oral drugs, easy to administer, and patients like it, it will certainly increase its market share” – UK key opinion leader
"根据其市场接受速度，随着我们在 Janus 激酶抑制剂使用经验的积累，我认为由于它们是口服药物、使用方便且患者青睐，其市场份额必将提升。"——英国关键意见领袖

“When I said that my crystal ball position is that the orals will take a big chunk of the market share from biologics, I feel equally strongly that combination therapy is going to be the pathway to the future.” – US key opinion leader
"当我预测口服药物将从生物制剂手中夺取大量市场份额时，我同样坚信联合治疗将成为未来的发展方向。"——美国关键意见领袖

“I think if enough oral biologics come out that are more effective and safe, I think there is easily a chance that that [orals overtaking biologics in patient coverage] could eventually happen. There is a lot of interest right now in developing so-called oral alpha-4/beta-7 integrin inhibitors, or oral IL-23 inhibitors, so there are people who are working on this stuff.” – US key opinion leader
“我认为如果有更多高效安全的口服生物制剂问世，口服药物在患者覆盖率上最终超越生物制剂的可能性很大。目前业界对开发口服α-4/β-7 整合素抑制剂和口服 IL-23 抑制剂非常热衷，确实有不少团队正在攻关。”——美国权威专家

Treatments for fibrosis and fistulas
纤维化与瘘管的治疗

Fistulas are a common, severe consequence of CD that may affect as many as 50% of CD patients within a 20-year timespan.
瘘管是克罗恩病（CD）常见且严重的并发症，约 50%的 CD 患者在 20 年内可能出现瘘管。

“And then, we don’t have anything that works on fibrosis in Crohn’s, so something that would help reduce or prevent stricture formation. And then the last thing would be, we don’t really have very good agents for fistulizing disease, so we need something a bit more for that… Maybe eventually about half [of patients have fibrosis]. There is some overlap there. Some of our fistulizing patients also get strictures as well.” – US key opinion leader
"其次，我们目前对克罗恩病纤维化束手无策，亟需能帮助减轻或预防狭窄形成的疗法。最后，针对瘘管型病变我们也缺乏非常有效的药物，这方面需要更多突破...可能最终约半数患者会出现纤维化。这两种情况存在交叉，部分瘘管患者同时也会发生肠道狭窄。" ——美国关键意见领袖

“[...] if we're looking at someone with fistulizing Crohn's disease, for instance, where there's essentially only one prospective study that has ever evaluated fistulizing disease, then infliximab, an anti-TNF molecule, is still the go-to therapy, because the others are all inferior to that.” – EU key opinion leader
"[...]举例来说，当我们观察一名患有瘘管型克罗恩病的患者时，实际上仅有一项前瞻性研究曾评估过瘘管型疾病，那么抗 TNF 分子英夫利昔单抗仍是首选疗法，因为其他疗法都逊色于它。"——欧盟关键意见领袖

“So, there are some studies under way to better understand fibrosis, and maybe also targeted in a specific way rather than saying, well, if there’s no inflammation then fibrosis can never arise, I think it’s a reality that it does arise in some patients, but then we need solutions for that. So, that’s one issue.” – US key opinion leader
"因此，目前正在进行一些研究以更好地理解纤维化，或许还能以特定方式靶向治疗，而不是简单认为没有炎症就不会出现纤维化。事实上某些患者确实会出现这种情况，我们需要为此寻找解决方案。这是当前面临的一个问题。" ——美国关键意见领袖

“Some of these drugs, like the anti-TL1 and the anti-ALK5, are hanging their hat a bit on what they call antifibrotic activity, and I’m not very enthusiastic about that for two reasons. First of all, the strictures in Crohn’s disease are not primarily fibrous tissue […]. And second, I’m concerned even if it does work, even if it does inhibit fibrosis, fibrosis is a healing mechanism, and are we going to go from strictures to penetration and to fistulas? I’m not sure.” – US key opinion leader
“像抗 TL1 和抗 ALK5 这类药物，它们主打所谓的抗纤维化活性，但我对此持保留态度。首先，克罗恩病的狭窄病变本质上并非纤维组织[...]；其次，即便真能抑制纤维化，纤维化本身是愈合机制，我担心会从狭窄病变恶化为穿透性病变或瘘管，这存在不确定性。”——美国权威专家

“The injection of stem cells for perianal fistula I think for sure has a good future. I mean, they’ve used all kinds of other things, gels and jellies, fat, all kinds of stuff. So, stem cells look as good or better than anything else so far.” – US key opinion leader
“干细胞注射治疗肛周瘘管肯定前景广阔。毕竟之前尝试过各种凝胶、脂肪填充等材料，而干细胞目前看来效果最佳。”——美国权威专家

Head-to-head trials  头对头临床试验

Currently, the CD space lacks head-to-head trial data, and demonstrating superiority against standard-of-care therapies would strengthen the positioning of upcoming drugs.
目前，克罗恩病治疗领域缺乏头对头临床试验数据，若能证明新药优于标准疗法，将显著提升其市场定位。

“Now, again it [mirikizumab] is being compared to Stelara, the big question will be how does it rate compared to Skyrizi? And I don’t think we’ll have a head-to-head trial right away. So, again, we’ll have to pore through the data very carefully.” – US key opinion leader
"现在，mirikizumab 再次与 Stelara 进行对比，关键问题在于它与 Skyrizi 相比表现如何？我认为短期内不会有头对头试验数据。因此我们必须非常仔细地研读现有数据。"——美国关键意见领袖

“We have very few head-to-head studies where we have somehow identified which patients benefit from what, so the only clues that you have there are that, for instance, extraintestinal manifestations like uveitis or arthritis, they usually benefit from anti-TNF compounds.” – EU key opinion leader
"我们几乎没有头对头研究能明确哪些患者适合哪种疗法，目前唯一线索是，像葡萄膜炎或关节炎这些肠外表现患者，通常对抗 TNF 制剂反应更好。"——欧盟关键意见领袖

“We don't have head-to-head comparisons except for risankizumab versus ustekinumab for second line, and versus Tremfya and ustekinumab. But that’s it.” – EU key opinion leader
"除了 risankizumab 与 ustekinumab 在二线治疗的对比数据，以及与 Tremfya 和 ustekinumab 的对比外，我们目前没有其他头对头研究数据。"——欧盟关键意见领袖

“There is no head-to-head comparison [of Skyrizi] with Stelara. So, it’s a slightly different molecule, but it works very well similarly to Stelara. So, I cannot compare it with ustekinumab because there isn’t a comparison which is published.” – UK key opinion leader
目前尚无[Skyrizi]与 Stelara 的头对头比较研究。虽然分子结构略有差异，但其疗效与 Stelara 非常相似。由于缺乏已发表的对比数据，我无法将其与乌司奴单抗进行直接比较。——英国关键意见领袖

Biosimilar uptake  生物类似药的市场渗透

Even more than a year after initial launch, many patients and physicians are still skeptical about the approved adalimumab biosimilars.
即便在上市一年多后，许多患者和医生仍对已获批的阿达木单抗生物类似药持怀疑态度。

“The issue with the US is nobody is incentivized to use a biosimilar, certainly not the provider, not the patient. The only person who benefits is the insurance company or the PBM. So, I’ll use it if I have to use it, but I’ll not go out of my way to use it. I’ll wait until somebody says, OK, you have to switch the patient to biosimilar A or biosimilar B.” – US key opinion leader
"美国的问题在于，使用生物类似药对任何人都没有激励作用——医生没有动力，患者也没有。唯一受益的是保险公司或药品福利管理机构。所以除非迫不得已，我不会主动选择使用。我会等到有人明确要求将患者转换到生物类似药 A 或 B 时再做决定。"——美国关键意见领袖

“I think this was a concern that people had in the beginning when biosimilars were approved. Now, practitioners are very comfortable with that, and actually very often they don't even know what kind of infliximab their patient is receiving. Very often, they don’t know, and this original fear of biosimilar is gone.” – US key opinion leader
“我认为这是生物类似药刚获批时人们的普遍担忧。如今临床医生对此已非常适应，实际上他们经常连患者使用的是哪种英夫利昔单抗都不清楚。这种对生物类似药最初的恐惧已经消失了。”——美国关键意见领袖

“I’m not incentivized in any way to prescribe a biosimilar, neither is the patient, so the patient’s preference is generally to just start branded Humira. So, if I put the prescription in and then I get a notification you have to prescribe a biosimilar, I’ll go ahead and do that.” – US key opinion leader
“无论是医生还是患者，目前都没有任何动力去选择生物类似药。患者通常更倾向于直接使用原研药修美乐。所以如果我开出原研药处方后收到必须改用生物类似药的通知，我也会遵照执行。”——美国关键意见领袖

“Yes, fear, I’m doing well on my current therapy, you’re rocking the boat. They’re not incentivized to switch, they’re afraid that the biosimilar is similar but it’s not exactly the same. So, there’s just fear of the unknown, and anecdotally, any time you switch a patient from the original to the biosimilar, there’s always a small percentage of patients who feel different, and they can’t explain – like just the other day I had a patient who said ever since you switched me to biosimilar, I’ve been depressed.” – US key opinion leader
“没错，就是恐惧心理——‘我目前的治疗方案效果很好，你们为什么要节外生枝’。患者没有换药的动力，他们担心生物类似药虽然相似但并非完全相同。这种对未知的恐惧确实存在，而且据观察，每当把患者从原研药转换到生物类似药时，总有一小部分患者会感觉异常却又无法解释——就像前几天有个病人跟我说‘自从换成生物类似药后，我就一直情绪低落’。”——美国关键意见领袖