• The rheumatoid arthritis market is set to experience increasing attrition due to biosimilar competition. The EU market has taken the brunt of biosimilar erosion, with earlier launches and more acceptance of biosimilars compared to other regions. Over time, biosimilar penetration is anticipated to gain more momentum as international real-world evidence builds, with long-term data supporting biosimilar efficacy and safety. This should allow physicians and patients to grow their confidence and familiarity with biosimilars, encouraging uptake.
  由于生物类似药的竞争，类风湿性关节炎市场将面临日益加剧的市场侵蚀。欧盟市场首当其冲受到生物类似药冲击，与其他地区相比，欧盟更早批准生物类似药上市且接受度更高。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进一步加速。这将增强医生和患者对生物类似药的信心与熟悉度，从而促进其使用。

• Nevertheless, as the RA caseload enlarges and several pipeline drugs launch, this will provide impetus for market growth. In 2024, there were approximately 4.5 million diagnosed prevalent cases of RA in the US, Japan and five major European markets (France, Germany, Italy, Spain and the UK), with 35.3% of cases in the US alone. By 2042, the number of prevalent cases in these markets is expected to grow to 5.2 million cases.
  尽管如此，随着类风湿性关节炎病例数量的增加以及多款在研药物的上市，市场增长仍将获得动力。2024 年，美国、日本及欧洲五大主要市场（法国、德国、意大利、西班牙和英国）的确诊患病病例数约为 450 万例，其中仅美国就占 35.3%。到 2042 年，这些市场的患病病例数预计将增长至 520 万例。

• As multibillion-dollar products, Humira and Enbrel represent the best-selling brands in the market, but since Humira's 2023 patent expiry in the US, 10 adalimumab biosimilars with discounts ranging from 5% to 85% have slowly begun to chip away at the originator brand's stronghold. However, etanercept biosimilars remain held in patent litigation, potentially giving Enbrel until 2029 before it could face the same fate as Humira.
  作为价值数十亿美元的产品，修美乐和恩利曾是市场上最畅销的品牌，但自 2023 年修美乐在美国专利到期后，10 款折扣幅度从 5%到 85%不等的阿达木单抗生物类似药已开始逐步蚕食原研药的市场主导地位。而依那西普生物类似药仍受专利诉讼制约，这可能使恩利在 2029 年前都不会面临与修美乐相同的命运。

• While the JAK inhibitors are differentiated by their convenient oral administration, their labels also contain a class-wide boxed warning for an increased risk of major adverse cardiovascular events (MACE), thrombosis, serious infections, and malignancies. These therapies are also limited to patients who have not responded to or cannot tolerate one or more TNF blockers for currently labeled indications, eliminating the potential for first line usage. While many predicted that these safety concerns could bar this class from garnering any substantial market share, the patient and physician desire for convenience and oral administration won out and so, in patients without cardiac risk factors, JAK inhibitors remain a key player in the RA space.
  虽然 JAK 抑制剂因便捷的口服给药方式形成差异化优势，但其药品说明书均带有统一的黑框警告，提示可能增加主要不良心血管事件（MACE）、血栓形成、严重感染和恶性肿瘤的风险。根据现有适应症标签，这些疗法仅限用于对一种或多种 TNF 抑制剂应答不足或不耐受的患者，因此无法成为一线用药。尽管许多人预测这些安全隐患会阻碍该类药物获得可观市场份额，但患者和内科医生对便捷口服治疗的诉求最终占据上风——对于无心血管风险因素的患者，JAK 抑制剂仍是类风湿关节炎领域的重要治疗选择。

• AbbVie has positioned Rinvoq, a JAK inhibitor approved in 2019, as a follow-on product from Humira. Supported by an extensive global pivotal trial program, as well as data demonstrating Rinvoq’s superiority in head-to-head trials with gold-standard Humira, AbbVie’s experience and presence in the RA market continues to foster success for the drug, despite its third-to-market status. Moreover, data showing that the safety risks of Rinvoq are similar to Humira and potentially better than other JAK inhibitors have supported rising usage.
  艾伯维将 2019 年获批的 JAK 抑制剂瑞福®（Rinvoq）定位为修美乐的后续产品。凭借全球关键临床试验项目的强力支持，以及瑞福®在头对头试验中展现出的对金标准药物修美乐的优越性数据，艾伯维在类风湿关节炎市场的丰富经验和强大影响力持续推动该药物取得成功，尽管其上市时间位列第三。此外，数据显示瑞福®的安全风险与修美乐相当，且可能优于其他 JAK 抑制剂，这进一步促进了其使用率的提升。

• AnaptysBio’s rosnilimab has showed notable efficacy and an unusually benign safety profile through week 12 in the Phase II RENOIR trial. Although more information is still needed to assess durability and long-term safety, as many of the concerns associated with RA drugs likely take longer than 12 weeks to present, the numerical superiority demonstrated efficacy and safety endpoints could give rosnilimab the edge if it is equally successful in Phase III.
  AnaptysBio 公司的 rosnilimab 在 II 期 RENOIR 试验中展现出显著疗效和异常良好的安全性（截至 12 周）。虽然评估持续性和长期安全性仍需更多数据（因为类风湿关节炎药物的许多潜在问题通常需要超过 12 周才能显现），但该药物在疗效和安全性终点指标上表现出的数值优势，若能在 III 期试验中取得同等成功，将使其具备显著竞争优势。

• There remains an unmet need for safer drugs, however; out of the current array of RA drugs, Orencia is the only agent without a boxed warning. Additionally, the use of specialty drugs has become a significant financial burden on healthcare systems and patients, so there is a pressing need for therapies that are both cost-effective and at least as safe as the current therapies, while still providing substantial efficacy.
  然而，对更安全药物的需求仍未得到满足；在当前所有类风湿关节炎药物中，奥瑞西珠单抗是唯一不带黑框警告的制剂。此外，专科药物的使用已成为医疗系统和患者沉重的经济负担，因此亟需开发兼具成本效益、安全性至少与现有疗法相当，同时仍能提供显著疗效的治疗方案。

Definition  定义

RA is a chronic, systemic inflammatory autoimmune disease that primarily damages the joints, leading to disability and increased mortality. RA affects approximately 1% of the global population.
类风湿关节炎是一种慢性、全身性炎症性自身免疫疾病，主要损害关节功能，导致残疾并增加死亡率。该疾病影响全球约 1%的人口。

RA typically presents with the following symptoms:
类风湿关节炎通常表现为以下症状：

• persistent joint stiffness, pain or swelling
  持续性的关节僵硬、疼痛或肿胀

• swelling commonly affecting the wrists, hands and feet
  肿胀通常影响手腕、手部和足部

• symmetrical symptoms affecting multiple joints bilaterally
  双侧多关节对称性症状

• symmetrical joint swelling with morning stiffness that lasts for at least 30 minutes
  对称性关节肿胀伴随晨僵，持续时间至少 30 分钟

Patients with persistent, inadequately treated symptoms may develop deformities and extra-articular manifestations that affect the whole body, as RA is a systemic illness. Patients often develop rheumatoid nodules (firm subcutaneous lumps) close to bony prominences. Complications may also be more serious, such as vasculitis, which is characterized by necrotizing inflammation of the blood vessels.
类风湿关节炎是一种全身性疾病，若患者症状持续未得到充分治疗，可能出现影响全身的关节畸形和关节外表现。患者常在骨突部位出现类风湿结节（坚硬的皮下肿块）。并发症也可能更为严重，例如以血管坏死性炎症为特征的血管炎。

Patient segmentation  患者分型

There is no standard definition of disease severity in treatment guidelines available for RA. Patients’ severity may range from remission to low, moderate or severe RA. Severity relates to the level of disease activity, as measured by a series of instruments such as the Patient Activity Scale (PAS), Routine Assessment of Patient Index, Clinical Disease Activity Index (CDAI), Disease Activity Score (DAS) and Simplified Disease Activity Index (SDAI).
目前针对类风湿关节炎的治疗指南中尚无疾病严重程度的统一定义。患者严重程度可从缓解期到轻度、中度或重度不等。严重程度与疾病活动水平相关，通常通过患者活动量表(PAS)、常规患者指数评估、临床疾病活动指数(CDAI)、疾病活动评分(DAS)和简化疾病活动指数(SDAI)等一系列工具进行测量。

2015 ACR treatment guidelines
2015 年美国风湿病学会治疗指南

The goal of treatment is low disease activity or remission. The 2015 American College of Rheumatology guidelines provide recommendations for the treatment of early and established RA. Early RA is defined as RA with duration of disease or symptoms of less than six months, with “duration” referring to the period of time that the patient has had symptoms or disease, and not the length of time since RA diagnosis. Established RA is defined as RA where the duration of disease or symptoms is equal to or greater than six months, or when the 1987 ACR RA classification criteria are met.
治疗目标是实现低疾病活动度或临床缓解。2015 年美国风湿病学会指南针对早期和确诊类风湿关节炎的治疗提供了建议。早期类风湿关节炎定义为病程或症状持续时间不足 6 个月的 RA 病例，其中"病程"指患者出现症状或疾病的时间段，而非自 RA 确诊之日起计算的时间。确诊类风湿关节炎则定义为病程或症状持续时间达到或超过 6 个月，或符合 1987 年 ACR RA 分类标准的病例。

2015 ACR recommendations for patients with symptomatic early RA
2015 年 ACR 针对有症状早期 RA 患者的治疗建议

2015 ACR recommendations for patients with established RA
2015 年 ACR 针对已确诊 RA 患者的治疗建议

2021 ACR treatment guidelines
2021 年美国风湿病学会治疗指南

In March 2021, the ACR provided an update to clinical practice guidelines for RA. The recommendations address treatment with:
2021 年 3 月，美国风湿病学会更新了类风湿关节炎临床实践指南。该指南针对以下治疗方案提出建议：

1. csDMARDs, biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)
1. 传统合成改善病情抗风湿药（csDMARDs）、生物制剂改善病情抗风湿药（bDMARDs）及靶向合成改善病情抗风湿药（tsDMARDs）

2. glucocorticoids  2. 糖皮质激素

3. use of these medications in certain high-risk populations, including patients with subcutaneous nodules, pulmonary disease, heart failure, lymphoproliferative disorder, hepatitis B infection, non-alcoholic fatty liver disease (NAFLD), persistent hypogammaglobulinemia without infection, previous serious infection and nontuberculous mycobacterial lung disease
3. 这些药物在特定高风险人群中的使用，包括皮下结节患者、肺部疾病患者、心力衰竭患者、淋巴增殖性疾病患者、乙型肝炎感染患者、非酒精性脂肪性肝病（NAFLD）患者、无感染的持续性低丙种球蛋白血症患者、既往严重感染患者以及非结核分枝杆菌肺病患者

Recommendation statements in the 2021 ACR treatment guidelines are not directly comparable to the 2015 guidelines as they did not retain the “early” versus “established” subgroups used in the prior update. The 2021 guidelines also provide recommendations that differ from what was seen in the previous update. Notable differences between the 2015 and 2021 guidelines include the following.
2021 年美国风湿病学会（ACR）治疗指南中的推荐声明与 2015 年指南无法直接比较，因其未沿用先前更新中使用的"早期"与"确立期"亚组分类。2021 年指南还提供了与之前更新不同的治疗建议。2015 年与 2021 年指南之间的显著差异包括以下方面。

EULAR treatment guidelines
欧洲抗风湿病联盟治疗指南

European Alliance of Associations for Rheumatology (EULAR) guidelines released in 2016 for the management of RA recommend that tsDMARDs, such as JAK inhibitors, should be considered for patients after the failure of one csDMARD. It is recommended that if the first csDMARD strategy, which is typically methotrexate, fails to achieve treatment target and poor prognostic factors are present, then a bDMARD or a tsDMARD should be added. While, in theory, this translates to access to a larger patient pool at earlier lines of therapy for tsDMARDs, we believe that the use of tsDMARDs largely depends on their overall cost effectiveness. 
2016 年发布的欧洲抗风湿病联盟（EULAR）类风湿关节炎管理指南建议，对一种传统合成改善病情抗风湿药（csDMARD）治疗失败的患者应考虑使用靶向合成改善病情抗风湿药（tsDMARD），如 JAK 抑制剂。若首选 csDMARD（通常为甲氨蝶呤）未能达到治疗目标且存在不良预后因素时，建议联用生物制剂 DMARD 或 tsDMARD。虽然理论上这能使更多患者在更早治疗阶段使用 tsDMARD，但我们认为 tsDMARD 的实际使用很大程度上取决于其整体成本效益。

Furthermore, the updated guidelines stress that bDMARDs and tsDMARDs should be used in combination with methotrexate, where possible. This change in recommendation was due to the EULAR taskforce’s belief that there was compelling evidence that all bDMARDs have better clinical, functional and structural outcomes in combination with csDMARDs, especially methotrexate. 
此外，更新后的指南强调，在可能的情况下，bDMARDs 和 tsDMARDs 应与甲氨蝶呤联合使用。这一建议的变更源于 EULAR 工作组认为，有充分证据表明所有 bDMARDs 与 csDMARDs（尤其是甲氨蝶呤）联用时，能获得更好的临床、功能和结构改善效果。

In the most recent update, made in 2022, the guidelines were altered to also include greater use of JAK inhibitors and IL-6 inhibitors, which are recommended when more established therapies such as methotrexate and DMARDs have not achieved treatment targets.
在 2022 年的最新更新中，指南进行了调整，纳入了对 JAK 抑制剂和 IL-6 抑制剂的更广泛使用建议。当甲氨蝶呤和 DMARDs 等更成熟的疗法未能达到治疗目标时，推荐使用这些药物。

2016 EULAR recommendations for the management of RA
2016 年 EULAR 类风湿关节炎管理建议

2019 EULAR recommendations for the management of RA
2019 年 EULAR 类风湿关节炎管理建议

In 2019, updated EULAR guidelines provided slight modifications to three recommendations. The first seven recommendations, as well as recommendations 9 and 12, remained unchanged.
2019 年更新的 EULAR 指南对三项建议进行了细微调整。前七项建议以及第 9 和第 12 项建议保持不变。

2022 EULAR recommendations for the management of RA
2022 年 EULAR 类风湿关节炎管理建议

The 2022 update to EULAR’s recommendations was quite similar to those from 2019. A small addition was made to recommendation 8 to include JAK inhibitors, and to recommendation 10 to include IL-6 inhibitors. Additionally, the previous recommendations 11 and 12 were combined together in this latest iteration.
2022 年更新的 EULAR 建议与 2019 年版非常相似。对建议 8 进行了小幅补充，增加了 JAK 抑制剂的内容；建议 10 则补充了 IL-6 抑制剂相关内容。此外，新版将原先的第 11 和 12 项建议合并为一条。

Last Reviewed:  最后审阅日期：
29 Jul, 2024  2024 年 7 月 29 日

by Swettha Mahesarajah  作者：斯维塔·马赫萨拉贾

Overview  概述

Methodology  方法论

We conducted an extensive literature review to identify epidemiological studies reporting the diagnosed prevalence of RA in the US, Japan and five major European markets. Searches were conducted in PubMed and Google Scholar. Potential data sources were critically appraised to provide a robust foundation on which to model and forecast the patient population of RA.
我们开展了广泛的文献综述，以识别报告美国、日本及欧洲五大主要市场类风湿关节炎（RA）确诊患病率的流行病学研究。检索范围涵盖 PubMed 和 Google Scholar 学术数据库。通过对潜在数据源进行严格评估，为 RA 患者群体的建模与预测奠定了可靠基础。

Diagnosed prevalent cases among individuals aged 15+ years were included in the forecast. Juvenile RA is not included in this analysis. Where available, age-specific prevalence data were extracted. For some countries, age-specific prevalence rates were extrapolated from another, appropriate country. We dynamically modeled age-specific prevalence rates instead of utilizing a static model, employing an in-house VBA model. Gender-specific prevalence data and assumptions were considered and applied as the disease burden is significantly higher in females compared to males.
预测模型纳入了 15 岁及以上人群的确诊患病病例。幼年型类风湿关节炎未包含在本分析中。在数据可得的情况下，我们提取了年龄别患病率数据。针对部分国家，其年龄别患病率数据是从其他合适国家的数据推算得出。我们采用自主研发的 VBA 模型进行动态建模，而非使用静态模型来测算年龄别患病率。鉴于女性疾病负担显著高于男性，模型中还纳入并应用了性别别患病率数据及相关假设。

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。

Sources used for the epidemiological analysis of RA in the US, Japan and five major European markets, by country
美国、日本及欧洲五大市场类风湿性关节炎流行病学分析所用资料来源（按国家/地区划分）

Disease definition  疾病定义

To provide a robust estimate and forecast for the prevalence of RA in the US, Japan and five major European markets, studies reporting on the diagnosed prevalence of RA were searched in PubMed, Google Scholar and reference lists of articles. Only studies that reported diagnosed cases of RA were considered. The definitions of RA varied by study; however, most studies included diagnosed cases defined according to a combination of disease codes (e.g., ICD-9 code 714.0, ICD-10 code M06.9), RA disease classification criteria (e.g., ACR 2010 criteria), a number of physician visits within a specified time period, and/or the number of prescriptions for RA drug therapies.
为提供美国、日本及欧洲五大主要市场 RA 患病率的可靠估算与预测，研究团队通过 PubMed、Google 学术及文献参考文献列表检索了关于 RA 诊断患病率的研究报告。仅纳入报告 RA 确诊病例的研究。各研究对 RA 的定义存在差异，但多数研究纳入的确诊病例需满足以下部分或全部标准：疾病编码组合（如 ICD-9 编码 714.0、ICD-10 编码 M06.9）、RA 疾病分类标准（如 ACR 2010 标准）、特定时间段内的内科医生就诊次数和/或 RA 药物治疗处方数量。

Country-specific methods  国别研究方法

US  美国

We extracted diagnosed prevalence data from Hunter et al. (2017). This study provided a prevalence range (0.52–0.55%) as it analyzed data from two separate US healthcare claims databases. Gender-specific diagnosed prevalence for individuals aged 18+ years was averaged from the two databases. Age-specific prevalence proportions were unavailable. We dynamically modeled age-specific prevalence rates instead of utilizing a static model, employing an in-house VBA model.
我们从 Hunter 等人（2017 年）的研究中提取了确诊患病率数据。该研究提供了 0.52%-0.55%的患病率范围，因其分析数据来自两个独立的美国医保索赔数据库。18 岁以上人群的性别确诊患病率取两个数据库的平均值。未能获取分年龄段的患病比例数据。为此我们采用内部 VBA 模型进行动态建模，推算了分年龄段的患病率，而非使用静态模型。

Japan  日本

Prevalence proportions from Nakajima et al. (2020) were derived using the population estimates for the year 2017. We were unable to gain access to the age- and gender-specific proportions provided in the study by Nakajima et al., so therefore employed the age- and gender-specific prevalence rates provided by Hunter et al. to calculate age- and gender-specific ratios. These ratios were then applied to derive age- and gender-specific prevalence rates for Japan.
中岛等人（2020 年）研究中的患病率比例基于 2017 年人口估算数据得出。由于无法获取该研究提供的分年龄和性别的具体比例数据，我们采用了亨特等人研究中的分年龄和性别患病率来计算相应比率，进而推算出日本的分年龄和性别患病率。

France  法国

Prevalence proportions were extracted from Vegas et al. (2023). We were unable to gain access to the age- and gender-specific proportions provided in the study by Vegas et al., so therefore employed the age- and gender-specific prevalence rates provided by Rossini et al. to calculate age- and gender-specific ratios. These ratios were then applied to derive age- and gender-specific prevalence rates for France.
维加斯等人（2023 年）研究中的患病率比例被直接采用。由于无法获取该研究提供的分年龄和性别的具体比例数据，我们采用了罗西尼等人研究中的分年龄和性别患病率来计算相应比率，进而推算出法国的分年龄和性别患病率。

Germany  德国

Age- and gender-specific prevalence proportions were extracted from Steffen et al. (2017). Annual age-specific ratios were calculated and applied to the corresponding year’s gender-specific prevalence proportions to approximate age- and gender-specific prevalence proportions for Germany.
施特芬等人（2017 年）研究中的分年龄和性别患病率比例被直接采用。通过计算年度分年龄比率并应用于对应年份的分性别患病率比例，最终估算出德国的分年龄和性别患病率比例。

Italy  意大利

Age- and gender-specific prevalence proportions were available from Rossini et al. (2014). We assumed diagnosed prevalence was comparable to the authors’ definition of confirmed RA only, which comprised both active RA and RA in remission. Individuals with unlikely RA were not considered in the overall prevalence proportion.
Rossini 等人(2014 年)的研究提供了按年龄和性别划分的患病率数据。我们假设确诊患病率仅等同于作者定义的"确诊类风湿关节炎"，包括活动期和缓解期病例。疑似病例未纳入总体患病率统计。

Spain  西班牙

Diagnosed cases were extracted from Silva-Fernández et al. (2020). Gender-specific ratios were applied to the overall population to approximate gender-specific prevalence proportions in Spain. Age-specific information was not available, so we therefore employed the age- and gender-specific prevalence rates provided by Rossini et al. to calculate the age- and gender-specific ratios.
确诊病例数据源自 Silva-Fernández 等人(2020 年)的研究。我们采用性别比例系数推算了西班牙分性别患病率。由于缺乏年龄分层数据，故采用 Rossini 等人提供的年龄-性别患病率来计算相应比例系数。

UK  英国

Prevalence proportions were extracted from Scott et al. (2022). We were unable to gain access to the age- and gender-specific proportions provided in the study by Scott et al., so therefore employed the age- and gender-specific prevalence rates provided by Rossini et al. to calculate age- and gender-specific ratios. These ratios were then applied to derive age- and gender-specific prevalence rates for the UK.
患病率数据引自 Scott 等人(2022 年)的研究。由于无法获取该研究中按年龄和性别划分的具体比例，我们采用 Rossini 等人提供的年龄-性别患病率来计算相应比例系数，进而推算出英国分年龄-性别的患病率数据。

Forecasting  预测方法

To calculate the number of total prevalent cases of RA in the 2023–43 forecast period, we multiplied extracted diagnosed 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 prevalent cases of RA were validated against national benchmarks where possible, to check for any inconsistencies or unusual trends in the analysis.
为计算 2023-2043 年预测期内类风湿性关节炎(RA)的总体患病病例数，我们将提取的确诊患病率比例与联合国《世界人口展望》数据库(United Nations, 2022)中各国分年龄、性别人口估算数据相乘。选择联合国数据库作为可靠的人口基数参考，该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。在可能的情况下，我们将预测的 RA 患病病例数与各国基准数据进行比对验证，以核查分析中是否存在不一致或异常趋势。

Last Reviewed:  最后审阅日期：
27 Jun, 2024  2024 年 6 月 27 日

by Emma Wille and Sonny Nghiem
作者：Emma Wille 与 Sonny Nghiem

Overview  概述

The RA market will decline slightly over the 2024–33 forecast period, with sales in the US, Japan and five major European markets ending at $21.9bn in 2033, decreasing slightly at an overall compound annual growth rate (CAGR) of -0.62%. Revenues in this market will peak at $24.8bn in 2028 due to increasing disease prevalence and uptake of newer drug classes, before decreasing as a whole because of biosimilar and generic erosion.
在 2024-2033 年预测期内，类风湿关节炎市场将小幅下滑，到 2033 年美国、日本和欧洲五大市场的销售额将达 219 亿美元，整体复合年增长率(CAGR)为-0.62%。由于疾病患病率上升和新药类别使用增加，该市场收入将在 2028 年达到 248 亿美元的峰值，随后因生物类似药和仿制药的冲击而整体下滑。

Key themes  关键主题

Anti-TNF inhibitors  抗 TNF 抑制剂

• Anti-TNF biologic brands will be negatively impacted by the launch of biosimilars during the forecast period, with leading brand Humira relinquishing its dominance of the RA market due to loss of exclusivity in the US. Both of the foremost brands, Humira and Enbrel, are forecast to show negative CAGRs (-8.8% and -7.3%, respectively) over 2024–33.
  在预测期内，抗 TNF 生物制剂品牌将受到生物类似药上市的负面影响，其中主导品牌修美乐因在美国失去独占权而放弃其在类风湿关节炎市场的统治地位。两大领先品牌修美乐和恩利预计在 2024-2033 年间均呈现负复合年增长率（分别为-8.8%和-7.3%）。

• However, Humira and Enbrel are still forecast to maintain more than a tenth of the RA market at the end of the forecast period. This is primarily due to etanercept biosimilars being held in patent litigation in the US, substantial originator rebates and exclusive contracting with payers until 2029. As a multibillion-dollar product, Humira represents the best-selling brand in the market, but the entry of 10 biosimilars in the US in 2023 will lead to a swift erosion of branded sales.
  然而，预计在预测期结束时，修美乐和恩利仍将占据类风湿关节炎市场超过十分之一的份额。这主要归因于依那西普生物类似药在美国陷入专利诉讼、原研药提供大幅折扣，以及与支付方签订独家合约至 2029 年。作为价值数十亿美元的产品，修美乐仍是市场上最畅销的品牌，但 2023 年美国市场 10 款生物类似药的上市将导致品牌药销售额迅速下滑。

• Additionally, in an effort to protect the company’s market share, AbbVie will continue to encourage switching from Humira to Rinvoq. In 2016, Humira and Enbrel were among the biggest-selling brands in the RA space, with blockbuster sales of $3.6bn and $4.5bn, respectively, together accounting for approximately 50% of RA sales.
  此外，为保护公司市场份额，艾伯维将继续推动患者从修美乐转向瑞福。2016 年，修美乐和恩利曾是类风湿关节炎领域最畅销的品牌药，分别创下 36 亿美元和 45 亿美元的惊人销售额，合计约占该领域总销售额的 50%。

• Because the launch of biosimilar etanercept in the US is dependent on successful litigation relating to multiple patents protecting Enbrel’s market exclusivity until 2029, we assume that biosimilar etanercept will launch in the US market towards the end of the forecast period. As such, erosion of the brand during the forecast period will be minimal, stemming mainly from competition from JAK inhibitor Rinvoq, generics of which will not be available until 2031, as well as from biosimilar adalimumab.
  由于美国生物类似药依那西普的上市取决于针对多项保护 Enbrel 市场独占权直至 2029 年的专利诉讼能否成功，我们预测该生物类似药将在预测期末段进入美国市场。因此原研药在预测期内的市场份额侵蚀将极为有限，主要竞争压力来自 JAK 抑制剂 Rinvoq（其仿制药 2031 年前不会上市）以及阿达木单抗生物类似药。

• Branded Remicade will continue to erode over the forecast period, reinforced by the entrance of Celltrion’s Remsima SC. The SC biosimilar was launched in the EU in February 2020 but has yet to be approved in the US.
  预测期内，品牌药 Remicade 的市场份额将持续下滑，这一趋势将因 Celltrion 公司皮下注射剂型 Remsima SC 的上市而加剧。该皮下注射生物类似药已于 2020 年 2 月在欧盟上市，但尚未获得美国批准。

• Ozoralizumab is a humanized, trivalent bispecific nanobody containing two human TNF-binding domains linked to a human serum albumin-binding domain. Ozoralizumab’s commercial potential is dampened by its late development compared to other marketed drugs targeting TNF as well as the geographic scope of its Phase III trial (ClinicalTrials.gov identifier: NCT04077567), which is limited to Japan despite global Phase II investigations. Because it is uncertain whether wider geographic development is under way, we have opted to forecast the drug only in Japan. Ozoralizumab launched in Japan in December 2022 and is forecast to reach $42m by 2033.
  奥佐拉珠单抗是一种人源化三价双特异性纳米抗体，包含两个与人类血清白蛋白结合域相连的人 TNF 结合域。由于相较于其他已上市的 TNF 靶向药物开发进度较晚，且其 III 期临床试验（ClinicalTrials.gov 标识符：NCT04077567）地理范围仅限于日本（尽管 II 期研究覆盖全球），该药物的商业潜力受到限制。鉴于尚不确定是否正在进行更广泛地域的开发，我们选择仅对日本市场进行预测。奥佐拉珠单抗于 2022 年 12 月在日本上市，预计到 2033 年销售额将达到 4200 万美元。

Cluster of differentiation (CD)-targeted monoclonal antibodies
CD（分化簇）靶向单克隆抗体

• Orencia’s method of use patents expired in 2022. However, there do not appear to be any abatacept biosimilars in development as of mid-2024, making it unlikely that any will enter the market during the forecast period.
  奥瑞珠单抗的使用方法专利已于 2022 年到期。但截至 2024 年年中，尚未有任何阿巴西普生物类似药在研，因此在预测期内不太可能有相关产品上市。

• Biosimilar rituximab, Truxima, was first approved in the US in May 2020 and is indicated to treat RA. Rituxan will experience losses as a result and will face further erosion from Rinvoq as well as biosimilar versions of well-established anti-TNFs.
  利妥昔单抗生物类似药 Truxima 于 2020 年 5 月首次在美国获批用于治疗类风湿性关节炎。这将导致利妥昔单抗原研药销售额下滑，并面临来自乌帕替尼及成熟抗 TNF 药物生物类似药的双重市场侵蚀。

IL-6 inhibitors  IL-6 抑制剂

• While the IL-6 receptor inhibitor Kevzara has demonstrated an overall positive clinical performance, we believe it is unlikely to capture significant market share due to its inability to distinguish itself from the first-to-market IL-6 receptor inhibitor Actemra. KOLs stress that a lack of direct head-to-head data against Actemra, alongside physician familiarity and brand loyalty with Actemra, will restrict the use of Kevzara unless it demonstrates greater cost effectiveness. The entrance of biosimilar tocilizumab also impacts both Actemra and Kevzara. However, Kevzara usage has still been growing, albeit more so in Japan and the five major European markets. This drug is forecast to peak in 2030, reaching $446m across the forecasted regions, before experiencing erosion due to sarilumab biosimilars from 2031 onwards.
  尽管 IL-6 受体抑制剂 Kevzara 展现出整体积极的临床效果，但我们认为其难以获得显著市场份额，因为它无法与首个上市的 IL-6 受体抑制剂 Actemra 形成差异化优势。关键意见领袖强调，由于缺乏与 Actemra 的直接头对头对比数据，加之内科医生对 Actemra 的熟悉度和品牌忠诚度，除非 Kevzara 能证明更具成本效益，否则其使用将受到限制。托珠单抗生物类似药的上市也对 Actemra 和 Kevzara 造成了冲击。不过 Kevzara 的使用量仍在增长，尤其是在日本和欧洲五大主要市场。预计该药物将在 2030 年达到 4.46 亿美元的销售峰值（覆盖所有预测地区），随后因 2031 年起上市的 sarilumab 生物类似药而逐渐萎缩。

• Artlegia is an intravenous drug by Russia’s R-Pharm and has been approved in Russia since 2020. A representative at the ACR Convergence in 2023 indicated that R-Pharm plans to submit a Biologics License Application (BLA) during 2024, and if approved, we expect the drug to enter in 2025 as a third-in-class IL-6 inhibitor. Artlegia’s late entry to the market is a disadvantage considering it will have biosimilar tocilizumab, which was approved in 2023 in the US and EU and is expected to reach Japan in 2025, along with other well-established brands to compete with. Artlegia’s commercial attractiveness is also hampered by its lack of differentiation from marketed IL-6 inhibitors, and it will likely be considered a “me-too” product. The drug is anticipated to reach $361m in sales within the forecasted regions by 2033.
  Artlegia 是俄罗斯 R-Pharm 公司研发的静脉注射药物，自 2020 年起在俄罗斯获批上市。2023 年 ACR Convergence 会议上，公司代表表示计划于 2024 年提交生物制品许可申请（BLA），若获批，预计该药物将于 2025 年作为第三款 IL-6 抑制剂上市。考虑到 Artlegia 上市时需面对 2023 年已在欧美获批、预计 2025 年进入日本市场的托珠单抗生物类似药，以及其他成熟品牌的竞争，其市场进入时机处于劣势。由于与已上市 IL-6 抑制剂缺乏差异化优势，该药物的商业吸引力受限，很可能被视为"me-too"产品。预计到 2033 年，该药物在预测区域的销售额将达到 3.61 亿美元。

JAK inhibitors  JAK 抑制剂

• Despite the safety warning issued by the FDA for this class in 2019, KOLs in both the US and UK report that JAK inhibitors are widely liked by patients due to their convenient oral formulation. The FDA’s safety warning due to the outcomes of the post-marketing ORAL Surveillance study (ClinicalTrials.gov identifier: NCT02092467) covers the entire JAK inhibitor class, although the study itself focused only on Xeljanz. Consequently, Xeljanz will remain less popular. However, as a class, Rinvoq, Jyseleca, Xeljanz and Olumiant will peak at $9.4bn in 2032, representing 39% of the market.
  尽管食品药品监督管理局在 2019 年对该类药物发布了安全警告，但美国和英国的医学专家表示，JAK 抑制剂因其便捷的口服剂型仍广受患者欢迎。虽然 ORAL Surveillance 上市后研究（ClinicalTrials.gov 编号：NCT02092467）仅针对 Xeljanz 开展，但食品药品监督管理局基于该研究结果发布的安全警告覆盖了整个 JAK 抑制剂类别，这将导致 Xeljanz 持续遇冷。不过作为一类药物，Rinvoq、Jyseleca、Xeljanz 和 Olumiant 的销售额将在 2032 年达到 94 亿美元峰值，占据 39%的市场份额。

• The beginning of the COVID-19 pandemic, which made in-person infusion appointments challenging and risky for some patients, also contributed to the rise of JAK inhibitors, as has AbbVie’s push for Rinvoq usage in the aftermath of Humira’s loss of exclusivity in the US. We expect sales of Rinvoq, Jyseleca and Olumiant to increase until generics for Rinvoq and Olumiant enter the market.
  新冠疫情的爆发使得部分患者难以安全进行输液治疗，这助推了 JAK 抑制剂的崛起；同时艾伯维在修美乐美国市场独占权失效后大力推广 Rinvoq 也起到促进作用。我们预计 Rinvoq、Jyseleca 和 Olumiant 的销售额将持续增长，直至 Rinvoq 与 Olumiant 的仿制药上市。

• The newest JAK entrant to the EU and Japanese markets, Jyseleca, is forecast to peak at $259m in 2033. The FDA issued a complete response letter in August 2020 due to concerns regarding the overall benefit/risk profile of the 200mg dose and requested data from the MANTA-RAy testicular safety trial, which led to Gilead’s decision not to advance Jyseleca for RA in the US. In our view, Jyseleca has not differentiated itself enough from the other JAK inhibitors and may be perceived as a “me-too” drug. Its late entry into the market after Olumiant, Rinvoq and Xeljanz also puts the drug at a disadvantage.
  最新进入欧盟和日本市场的 JAK 抑制剂 Jyseleca 预计将在 2033 年达到 2.59 亿美元的销售峰值。由于对 200mg 剂量整体获益/风险比的担忧，食品药品监督管理局于 2020 年 8 月发出完整回复函，要求提供 MANTA-RAy 睾丸安全性试验数据，这导致吉利德决定不在美国推进 Jyseleca 用于类风湿关节炎的治疗。我们认为，Jyseleca 与其他 JAK 抑制剂的差异化不足，可能被视为"仿制型"药物。其在 Olumiant、Rinvoq 和 Xeljanz 之后较晚进入市场也使其处于竞争劣势。

• We forecast Rinvoq to be the most commercially successful JAK inhibitor in RA, with an estimated peak of approximately $8.6bn in 2032 before the entrance of generic upadacitinib in 2033 in the US. Growth across the forecast period is in part due to AbbVie’s marketing campaign in the wake of biosimilar entrants for Humira. Rinvoq gained approval in the US, EU and Japan in August 2019, December 2019 and January 2020, respectively, supported by AbbVie’s extensive global pivotal program. The drug has demonstrated superiority in head-to-head trials against Humira as well as Orencia, which has given physicians increased confidence.
  我们预测 Rinvoq 将成为类风湿关节炎领域最成功的 JAK 抑制剂，预计在 2033 年美国仿制药 upadacitinib 上市前，其销售额将在 2032 年达到约 86 亿美元的峰值。预测期内的增长部分归功于艾伯维在 Humira 生物类似药上市后开展的营销活动。Rinvoq 分别于 2019 年 8 月、12 月和 2020 年 1 月在美国、欧盟和日本获批上市，这得益于艾伯维全球关键性临床试验项目的支持。该药物在与 Humira 和 Orencia 的头对头试验中均显示出优越性，这增强了医生的处方信心。

Q2 2024 model updates  2024 年第二季度模型更新

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

• Biosimilar golimumab added
  新增戈利木单抗生物类似药

• Market shares adjusted for all drugs
  所有药品调整后的市场份额

• Olumiant Japan loss of exclusivity updated to March 2029
  Olumiant 日本市场独占权到期时间更新至 2029 年 3 月

• Xeljanz US, EU, and Japan losses of exclusivity updated to December 2025, December 2028, and 2025, respectively
  Xeljanz 在美国、欧盟和日本的独占权到期时间分别更新至 2025 年 12 月、2028 年 12 月和 2025 年

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

• ABBV-154 forecast removed
  移除 ABBV-154 预测数据

• Otilimab forecast removed
  移除奥替利单抗预测数据

• Enbrel US loss of exclusivity changed to 2029
  修美乐美国市场独占权到期时间调整为 2029 年

• Kevzara US, EU, and Japan loss of exclusivity changed to 2031
  Kevzara 在美国、欧盟和日本的独家权丧失时间调整为 2031 年

• Rinvoq loss of exclusivity added as 2031 for US and 2029 for EU
  Rinvoq 新增独家权丧失时间：美国 2031 年，欧盟 2029 年

• Xeljanz US and EU loss of exclusivity changed to 2034
  Xeljanz 在美国和欧盟的独家权丧失时间调整为 2034 年

• Ozoralizumab Japan launch changed to 2023
  Ozoralizumab 在日本上市时间调整为 2023 年

• Ozoralizumab Japan loss of exclusivity added as 2032
  日本奥佐利珠单抗独占权到期时间调整为 2032 年

• Biosimilar tocilizumab Japan launch changed to 2025
  日本托珠单抗生物类似药上市时间改为 2025 年

• Simponi Japan loss of exclusivity removed
  日本欣普尼独占权到期信息已删除

• Biosimilar etanercept US launch date delayed to 2029
  美国依那西普生物类似药上市日期推迟至 2029 年

• Artlegia launch date delayed to 2023
  Artlegia 上市时间推迟至 2023 年

• Biosimilar tocilizumab launch date delayed to 2023
  托珠单抗生物类似药上市时间推迟至 2023 年

• Actemra forecast adjusted lower
  Actemra 销售预测下调

• Cimzia forecast adjusted higher
  Cimzia 销售预测上调

• Enbrel forecast adjusted lower
  恩博（Enbrel）销售预测下调

• Humira forecast adjusted lower
  修美乐（Humira）销售预测下调

• Jyseleca forecast adjusted higher
  捷抑瑞（Jyseleca）销售预测上调

• Kevzara forecast adjusted higher
  凯泽诺（Kevzara）销售预测上调

• Olumiant forecast adjusted higher
  奥乐松（Olumiant）销售预测上调

• Orencia forecast adjusted higher
  欧泰乐（Orencia）销售预测上调

• Remicade forecast adjusted lower
  类克（Remicade）销售预测下调

• Rinvoq forecast adjusted higher
  瑞福（Rinvoq）销售预测上调

• Simponi forecast adjusted lower
  Simponi 预期销售额下调

• Xeljanz forecast adjusted lower
  Xeljanz 预期销售额下调

• Rituxan forecast adjusted lower
  Rituxan 预期销售额下调

• Artlegia forecast adjusted higher
  Artlegia 预期销售额上调

• Biosimilar adalimumab forecast adjusted higher
  生物类似药阿达木单抗销售预测上调

• Biosimilar etanercept forecast adjusted higher
  生物类似药依那西普销售预测上调

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

• Biosimilar tocilizumab forecast adjusted higher
  生物类似药托珠单抗销售预测上调

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

• 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

• Actemra forecast adjusted lower
  Actemra 销售预测下调

• Humira forecast adjusted lower
  Humira 销售预测下调

• Jyseleca forecast adjusted lower
  Jyseleca 销售预测下调

• Kevzara forecast adjusted lower
  Kevzara 销售预测下调

• Orencia forecast adjusted higher
  奥瑞西娅（Orencia）销售预测上调

• Rinvoq forecast adjusted higher
  瑞福乐（Rinvoq）销售预测上调

• Rituxan forecast adjusted higher
  利妥昔（Rituxan）销售预测上调

• Xeljanz forecast adjusted higher
  尚杰（Xeljanz）销售预测上调

• Biosimilar adalimumab forecast adjusted higher
  生物类似药阿达木单抗销售预测上调

• Biosimilar infliximab forecast adjusted lower
  生物类似药英夫利昔单抗销售预测下调

• Biosimilar rituximab forecast adjusted lower
  生物类似药利妥昔单抗销售预测下调

• ABBV-154 approval dates delayed to 2030
  ABBV-154 获批日期推迟至 2030 年

• Artlegia approval dates delayed to 2022
  Artlegia 获批日期推迟至 2022 年

• Otilimab approval dates delayed to H2 2023
  Otilimab 获批日期推迟至 2023 年下半年

• Ozoralizumab approval date delayed to 2023
  Ozoralizumab 获批日期推迟至 2023 年

• Biosimilar tocilizumab forecast added
  新增托珠单抗生物类似药预测

• Biosimilar abatacept forecast removed
  生物类似药阿巴西普预测数据已移除

Model updates (16 December 2020)
模型更新（2020 年 12 月 16 日）

• Jyseleca forecast removed in the US following Gilead’s decision to not pursue FDA approval in this indication
  由于吉利德公司决定不寻求食品药品监督管理局在该适应症上的批准，美国市场 Jyseleca 预测数据已移除

• Jyseleca forecast adjusted lower in 5EU and Japan
  5EU 地区及日本市场 Jyseleca 预测数据已下调

• Rinvoq forecast adjusted higher after AbbVie’s Immunology Strategy Update.
  艾伯维免疫学战略更新后，Rinvoq 销售预测上调。

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）

• Olokizumab’s name changed to Artlegia
  Olokizumab 更名为 Artlegia

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

• Enbrel forecast adjusted slightly higher
  恩利（Enbrel）销售预测小幅上调

• Humira forecast adjusted lower
  修美乐（Humira）销售预测下调

• Biosimilar adalimumab forecast adjusted lower
  阿达木单抗生物类似药销售预测下调

• Jyseleca forecast adjusted lower
  杰塞乐卡（Jyseleca）销售预测下调

• Kevzara forecast adjusted lower
  Kevzara 销售预测下调

• Olumiant forecast adjusted slightly lower
  Olumiant 销售预测微幅下调

• Rinvoq forecast adjusted higher
  Rinvoq 销售预测上调

• Rituxan forecast adjusted slightly lower
  Rituxan 销售预测微幅下调

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

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

Methodology  方法论

We use a patient-based approach to size the commercial potential of the RA treatment market across the US, Japan and five major European markets. Our analysis contains an assessment of key therapies designed to treat RA on the market and in the late-phase pipeline, a discussion of RA market dynamics and a 10-year patient-based sales forecast.
我们采用基于患者数量的方法，评估了美国、日本及欧洲五大主要市场类风湿关节炎治疗领域的商业潜力。分析内容包括：针对已上市及后期研发阶段关键疗法的评估、类风湿关节炎市场动态探讨，以及基于患者数量的十年销售预测。

Treatments for RA are generally perceived as clinically comparable. A critical differentiator between products is market access, which carries the most weight (alongside generic competition risk) within the commercial attributes of our drug assessment model. As specialty products, therapies for RA can be expensive, and formulary positioning is the principal determinant that drives prescribing.
类风湿关节炎(RA)治疗药物在临床上通常被认为效果相当。产品间的关键差异在于市场准入情况，这在我们药物评估模型的商业属性中（连同仿制药竞争风险）占据最大权重。作为专科药物，RA 疗法可能价格昂贵，而医保目录准入等级是影响处方决策的主要因素。

Marketed biologic DMARDs  已上市生物制剂 DMARDs

TNF inhibitors  TNF 抑制剂

Although the anti-TNF class possesses a iron grip on the market as the first line of biologic therapy in the RA treatment algorithm, a significant proportion of patients do not achieve clinical remission on these therapies and others lose response over time. US real-world studies indicate that most patients are prescribed an anti-TNF as their first targeted therapy and interviews with key opinion leaders suggest that the members of this class are considered relatively equivalent in efficacy and safety. Although ACR treatment guidelines recommend switching to another drug class, most patients (54.2–68.2%) are TNF-cyclers who are moved to alternative anti-TNF therapies following inadequate response and these drugs continue to be favored due to longstanding physician familiarity and prioritization in formularies.  However, they do not satisfy persisting unmet needs in the RA market for effective, affordable, and safe treatments that allow a large percentage of patients to achieve remission. Furthermore, the class has black box warnings for the risk of serious infections and malignancy.
尽管抗 TNF 类药物作为类风湿关节炎治疗算法中的一线生物疗法牢牢占据市场主导地位，但相当比例患者无法通过这些疗法达到临床缓解，另有部分患者会随时间推移出现疗效衰减。美国真实世界研究显示，大多数患者首次接受靶向治疗时会被开具抗 TNF 药物，而关键意见领袖访谈表明这类药物在疗效和安全性上被认为具有相对等效性。虽然美国风湿病学会治疗指南建议换用其他类别药物，但多数患者（54.2%-68.2%）会因疗效不足而转为其他抗 TNF 疗法（即 TNF 循环用药者），由于内科医生长期使用习惯和医保目录优先覆盖，这类药物仍被广泛选用。然而它们无法满足类风湿关节炎市场对高效、可及且安全疗法的持续未满足需求——这类疗法应能使大部分患者实现病情缓解。此外，该类药物还附有关于严重感染和恶性肿瘤风险的黑框警告。

• Enbrel (etanercept) is a well-established product as the first therapy approved for the treatment of RA. This recombinant fusion protein is marketed by Amgen and Pfizer, which have extensive commercial resources and marketing experience in the field. The crucial advantage for Enbrel is its preferred positioning in formularies that has been afforded by deep discounts and permits its prioritization in the treatment algorithm. Efficacy-wise, subcutaneous Enbrel with and without background methotrexate offers a 39-40% ACR50 at month six, with very low placebo response rates of 3-5%. Although anti-TNF therapies are generally accepted to have similar rates of infection, data from the RABBIT study indicate that Enbrel may be associated with lower rates of serious bacterial infection, like tuberculosis, compared to the other members of the anti-TNF class.
  恩利（依那西普）作为首个获批用于类风湿关节炎治疗的药物，已成为该领域的成熟产品。这款重组融合蛋白由安进和辉瑞联合销售，两家公司在生物制剂领域拥有丰富的商业资源和营销经验。恩利的关键优势在于通过大幅折扣获得的医保目录优先地位，使其在治疗算法中享有优先选用权。疗效方面，无论是否联合甲氨蝶呤背景治疗，皮下注射恩利在第六个月均可达到 39-40%的 ACR50 缓解率，而安慰剂组应答率仅为 3-5%。虽然抗 TNF 疗法普遍被认为具有相似的感染发生率，但 RABBIT 研究数据显示，相较于其他抗 TNF 类药物，恩利可能导致结核病等严重细菌感染的发生率更低。

• Unresolved patent litigation has prevented etanercept biosimilars from launching in the US, which will allow Enbrel to continue maximizing dividends from its commercial stronghold until 2028 or 2029, as etanercept biosimilars, such as Sandoz’s Erelzi and Samsung Bioepis’s Eticovo, are held in legal uncertainty. Although Elrezi, Benepali (the European version of Eticovo), and Lupin’s Nepexto have all launched in Europe starting in 2016, this extended patent protection in the US has earned Enbrel the highest commercial score.
  未解决的专利诉讼阻碍了依那西普生物类似药在美国上市，这使得恩利（Enbrel）能够持续从其商业堡垒中获取最大收益直至 2028 或 2029 年——山德士的 Erelzi 和三星 Bioepis 的 Eticovo 等依那西普生物类似药仍陷于法律不确定性中。尽管 Elrezi、Benepali（Eticovo 的欧洲版本）和 Lupin 的 Nepexto 自 2016 年起已陆续在欧洲上市，但美国延长的专利保护仍为恩利赢得了最高的商业评分。

• AbbVie managed to secure a leading position for Humira (adalimumab) in US formularies due to the brand’s broad label, which allows for deeper discounts for larger contracts with payers across multiple indications. The numerical efficacy of Humira is slightly lower than that of Enbrel, with an ACR50 of 35% as a monotherapy and 39% in combination with methotrexate. Placebo rates were higher in these Humira studies, so the placebo-adjusted difference is more stark (27% as a monotherapy and 29% with methotrexate), but Humira’s more convenient every-two-weeks dosing regimen and the more thorough array of clinical trials with higher patient counts give this drug a slightly higher clinical score than Enbrel.
  得益于广泛的适应症标签，艾伯维成功使修美乐（阿达木单抗）在美国医保目录中占据领先地位，这使其能够针对多种适应症与支付方签订更大规模的合同并提供更深度折扣。修美乐的数值疗效略低于恩利，单药治疗的 ACR50 为 35%，联合甲氨蝶呤治疗时为 39%。修美乐研究中的安慰剂应答率较高，因此安慰剂校正后的差异更为显著（单药 27%，联用甲氨蝶呤 29%），但修美乐每两周一次的给药方案更为便捷，且临床试验数量更全面、患者样本量更大，使得该药物的临床评分略高于恩利。

• Biosimilars referencing Humira became available in Europe in 2018 and saw moderately high uptake, foreshadowing the changes that rocked the US market beginning in January 2023 with Amgen’s Amjevita, the first of ten adalimumab biosimilars to enter the US market. Given the substantial number of biosimilars and the quickly changing dynamics as these products vie for market share, we have included a full analysis of the adalimumab biosimilar market in the next section.
  2018 年修美乐生物类似药在欧洲上市后获得了较高使用率，这预示着 2023 年 1 月安进公司的 Amjevita（首个进入美国市场的阿达木单抗生物类似药，共十款）引发美国市场震荡的变革。鉴于生物类似药数量庞大且各产品争夺市场份额导致市场格局快速变化，我们将在下一章节对阿达木单抗生物类似药市场进行全面分析。

• Cimzia (certolizumab) lacks an Fc domain, which prevents the drug from crossing the placenta, and as such, it is FDA-approved for use during pregnancy and breastfeeding. This has carved out a space in the market as very few RA drugs, including methotrexate, are considered safe for use in pregnant people. Cimzia’s ACR50 rate is lower than Enbrel and Humira, particularly in the context in which pregnant people may be taking it: as a monotherapy without background methotrexate (19% placebo-adjusted ACR50). However, the once or twice monthly dosing options and the subcutaneous administration offer convenience appreciated by this higher risk subpopulation.
  Cimzia（赛妥珠单抗）因缺乏 Fc 结构域而无法通过胎盘屏障，因此获得美国食品药品监督管理局批准可用于妊娠期和哺乳期。这一特性为其开辟了独特的市场空间——包括甲氨蝶呤在内，极少有类风湿关节炎药物被认为适合孕妇使用。尽管 Cimzia 的 ACR50 缓解率（19%的安慰剂校正值）低于恩利和修美乐，特别是在孕妇可能采用的单药治疗方案（不联合使用甲氨蝶呤）中表现更明显，但其每月 1-2 次的皮下给药方案为这类高风险人群提供了便利性优势。

• While Cimzia’s patents in Europe and the US expired in 2024, the manufacturing process is complicated for this PEGylated monoclonal antibody; just one biosimilar is in development, Xbrane’s XB003. It was originally licensed to Biogen, but the deal was terminated in August 2024, leaving Xbrane to search for another partner to help commercialize the drug. This has deferred the initiation of clinical trials so we do not expect biosimilar competition in the near future.
  虽然 Cimzia 在欧洲和美国的专利已于 2024 年到期，但这款聚乙二醇化单抗的生产工艺复杂——目前仅 Xbrane 公司的 XB003 一款生物类似药在研。该药物最初授权给渤健公司，但协议于 2024 年 8 月终止，Xbrane 需另寻合作伙伴推进商业化进程。这导致临床试验启动延迟，因此我们预计短期内不会面临生物类似药竞争。

• Unlike the first three anti-TNF therapies, Remicade (infliximab) is approved for RA only in combination with methotrexate. It is also available only as an infusion and provides the lowest placebo-adjusted ACR50, 22% at 30 weeks, earning it a below average clinical score despite offering one of the least frequent dosing schedules out of all assessed drugs (every other month). A meta-analysis also suggested that Remicade was significantly more likely than Enbrel, Humira, and Simponi to result in study withdrawals due to adverse events, further tempering its clinical score.
  与前三种抗 TNF 疗法不同，Remicade（英夫利昔单抗）仅被批准与甲氨蝶呤联合用于治疗类风湿性关节炎。该药物仅通过静脉输注给药，其 30 周时的安慰剂校正 ACR50 应答率最低（22%），尽管在所有评估药物中其给药频率最低（每两个月一次），临床评分仍低于平均水平。一项荟萃分析还表明，与 Enbrel、Humira 和 Simponi 相比，Remicade 因不良事件导致研究中止的发生率显著更高，这进一步降低了其临床评分。

• The drug faced sales erosion from biosimilar infliximab for many years, but the competition was taken to a fiercer level in November 2019, when Celltrion's Remsima SC, a subcutaneous version of infliximab, was approved by the European Medicines Agency to treat RA. This more convenient formulation is associated with lower disease activity rates and higher remission rates than the original Remsima IV. However, although the drug was approved in the US as Zymfentra in October 2023, Celltrion went through the stand-alone BLA process, so it is considered a new drug and not a biosimilar. It has only been approved for use in ulcerative colitis and Crohn’s disease in the US thus far. On the other hand, Inflectra, the US brand for Remsima IV, was approved as a biosimilar and can be used in all indications for which Remicade is approved, including RA.
  多年来，该药物一直面临生物类似药英夫利昔单抗的销售侵蚀，但 2019 年 11 月竞争升级至更激烈阶段——当时 Celltrion 公司的皮下注射剂型英夫利昔单抗 Remsima SC 获得欧洲药品管理局批准用于治疗类风湿关节炎。相比原研药 Remsima IV，这种更便捷的剂型与更低的疾病活动度及更高的缓解率相关。不过，尽管 2023 年 10 月该药以 Zymfentra 名称在美国获批，但 Celltrion 走的是独立生物制品许可申请流程，因此被视为新药而非生物类似药。目前在美国仅获批用于溃疡性结肠炎和克罗恩病两种适应症。另一方面，Remsima IV 的美国品牌 Inflectra 是作为生物类似药获批的，可用于包括类风湿关节炎在内的所有 Remicade 获批适应症。

• Like Remicade, Simponi (SC) and Simponi Aria (IV) (golimumab) is approved for RA in combination with methotrexate. Both formulations produced a 22-23% ACR50 rate at 24 weeks in patients on methotrexate, but the draw of this particular anti-TNF drug is the improved dosing scheme where the SC version is administered monthly and the IV version is administered every two months, making these golimumab products the most convenient member of its class. Patent protection on Simponi and Simponi Aria expired in 2024 and in January 2025, the FDA accepted Alvotech and Teva’s BLA for AVT05, biosimilar golimumab. The review process is expected to be completed in late 2025, so biosimilar erosion will begin to chip away at Simponi’s market share in 2026.
  与类克（Remicade）类似，优特克单抗皮下注射剂（Simponi SC）和静脉注射剂（Simponi Aria IV）（戈利木单抗）获批与甲氨蝶呤联用治疗类风湿关节炎。两种剂型在使用甲氨蝶呤的患者中 24 周时 ACR50 缓解率达 22-23%，但该抗 TNF 药物的优势在于改良给药方案——皮下制剂每月给药一次，静脉制剂每两月给药一次，使其成为同类产品中最便捷的戈利木单抗制剂。优特克单抗及其静脉剂型的专利保护分别于 2024 年和 2025 年 1 月到期，随后食品药品监督管理局受理了 Alvotech 与 Teva 公司生物类似药 AVT05（戈利木单抗生物类似药）的生物制品许可申请。审查程序预计 2025 年底完成，因此生物类似药将从 2026 年起逐步侵蚀优特克单抗的市场份额。

• The newest member of the anti-TNF class for RA is Nanozora (ozoralizumab), which was approved in Japan in September 2022. This drug is unique in that it is a humanized, trivalent bispecific nanobody containing two human TNF-binding domains linked to a human serum albumin-binding domain, which may offer a lower risk of inflammation at the subcutaneous injection site. In patients on background methotrexate, the drug produced a 47.8% placebo-adjusted ACR50 at 24 weeks, quite a bit higher than the other members of the anti-TNF class. However, Nanozora is not in active development outside of Japan and has therefore been excluded from our model.
  抗 TNF 类风湿性关节炎治疗药物家族的最新成员是 Nanozora（奥佐利珠单抗），该药于 2022 年 9 月在日本获批。这款药物的独特之处在于其为人源化三价双特异性纳米抗体，包含两个与人类血清白蛋白结合域相连的人源 TNF 结合域，可降低皮下注射部位的炎症风险。在使用背景药物甲氨蝶呤的患者中，该药在第 24 周时实现了 47.8%的安慰剂校正 ACR50 缓解率，显著高于其他抗 TNF 类药物。不过 Nanozora 目前仅在日本进行开发，因此未纳入我们的预测模型。

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. 
  过去两年间，阿达木单抗生物类似药的市场格局已发生剧变。这些生物类似药的核心差异在于药房福利管理公司（PBM）的报销覆盖范围，而上市时间、浓度、可互换性状态、定价策略及与分销商的商业合作似乎影响较小。2024 年 4 月，美国最大 PBM 之一 CVS Caremark 率先将原研药修美乐移出全国优选药品目录，替换为生物类似药版本。紧随这一趋势，2025 年 OptumRx 成为唯一保留修美乐的主要 PBM，但将其降至第三报销层级，需额外提供处方依据。值得注意的是，CVS Caremark 和 Express Scripts 的全国优选药品目录已纳入无品牌标识的阿达木单抗生物类似药。在报销政策调整过程中，随着生物类似药持续渗透，修美乐的市场地位开始松动。不过目前该原研药仍占据美国阿达木单抗市场约三分之二份额。 在已获批的阿达木单抗生物类似药中，海芮莫兹通过与 CVS 子公司 Cordavis 的合作获得了显著的市场份额，约占阿达木单抗市场的 15%，该合作推动了其进入 Caremark 优先处方集。

Speed to market   上市速度

• 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 
可互换性与浓度规格

• 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. 
  尽管高浓度配方（100mg/mL）占据 Humira 市场的主要份额，但许多获批生物类似药仅提供低浓度规格——浓度仅为原研药的一半。Amjevita、Cyltezo、Hadlima 和 Hyrimoz 同时推出两种浓度规格，而 Hulio、Yusimry、Idacio 和 Abrilada 仅提供低浓度版本。Simlandi 和 Yuflyma 则仅获批高浓度规格。值得注意的是，Hyrimoz 和 Simlandi 提供附带可互换性认定的高浓度制剂，为患者提供了减少注射体积的选择方案。

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。

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

'My concern about interchangeability or getting the attribute of interchangeability is immunologic.' — US rheumatology key opinion leader
"我对可互换性或获得可互换属性的担忧在于免疫原性。"——美国风湿病学关键意见领袖

'I feel like there are just so many [Humira biosimilars] that I could start somebody on one biosimilar in June, and by the next January they’re going to be on a completely different one, and then the next year they’re going to be on something different again.' — US rheumatology key opinion leader
"我感觉有太多[修美乐生物类似药]可选，我可能在 6 月让患者开始使用一种生物类似药，到次年 1 月他们就得换用完全不同的另一种，再过一年又要换成其他产品。"——美国风湿病学关键意见领袖

IL-6 inhibitors  IL-6 抑制剂

• Actemra (tocilizumab) was the first IL-6 inhibitor approved to treat RA. The product is available in both IV and SC formulations, with the latter offering a placebo-adjusted ACR50 rate of 28% at week 24 in patients taking background DMARDs. Like the anti-TNFs, Actemra’s FDA label contains a boxed warning for serious infections, but tolerability may be better for Actemra in terms of injection site reactions. Although Actemra had a first-to-market advantage, biosimilars are beginning to catch up after the drug’s loss of exclusivity in 2019. Bio-Thera Solutions, along with Biogen, announced positive Phase III results for Tofidence, their tocilizumab biosimilar, in June 2021, and the drug was approved in September 2023. This was soon joined by Fresenius Kabi's Tyenne in March 2024. While Tofidence is available only as an IV formulation, Tyenne is approved for both IV and SC routes of administration, which launched in April 2024 and July 2024, respectively. Further contributing to Actemra erosion, in February 2025, IV and SC forms of Celltrion’s Avtozma were approved in the US and Europe and are expected to launch in mid to late 2025.
  Actemra（托珠单抗）是首个获批用于治疗类风湿性关节炎的 IL-6 抑制剂。该产品提供静脉注射和皮下注射两种剂型，其中皮下注射剂型在使用背景 DMARDs 治疗的患者中，第 24 周时安慰剂校正后的 ACR50 应答率达到 28%。与抗 TNF 药物类似，Actemra 的食品药品监督管理局说明书中包含关于严重感染的黑框警告，但在注射部位反应方面，Actemra 的耐受性可能更优。尽管 Actemra 拥有先发上市优势，但自 2019 年专利到期后，生物类似药正迎头赶上。百奥泰与渤健合作开发的托珠单抗生物类似药 Tofidence 于 2021 年 6 月公布 III 期阳性结果，并于 2023 年 9 月获批上市。2024 年 3 月，费森尤斯卡比的 Tyenne 紧随其后获得批准。Tofidence 仅提供静脉注射剂型，而 Tyenne 则同时获批静脉和皮下注射两种给药途径，分别于 2024 年 4 月和 7 月上市。2025 年 2 月，Celltrion 的 Avtozma 静脉和皮下注射剂型在欧美获批，预计将于 2025 年中下旬上市，这将进一步加剧 Actemra 的市场份额流失。

• Kevzara (sarilumab) is not strongly differentiated from Actemra but did perform slightly worse in patients on background DMARDs than its class counterpart, showing a 22.6% placebo-adjusted ACR50 at 24 weeks. Both of these IL-6 inhibitors act at the receptor, as opposed to interacting with IL-6 itself, but the main difference is structural. While Actemra is a humanized antibody, Kevzara is fully human, which could theoretically offer a moderately better immunogenicity profile in the latter, although the rates of neutralizing antibodies were relatively similar in registrational trials. Kevzara’s patents last until 2028, although some indirect erosion from biosimilar tocilizumab is expected in the meantime.
  Kevzara（sarilumab）与 Actemra 相比差异化优势不明显，且在联合背景 DMARDs 治疗的患者中疗效略逊于同类产品，24 周时安慰剂校正后的 ACR50 应答率为 22.6%。这两种 IL-6 抑制剂均作用于受体层面（而非直接与 IL-6 相互作用），主要区别在于结构差异：Actemra 为人源化抗体，而 Kevzara 为全人源抗体——理论上后者可能具有相对更优的免疫原性特征，但注册试验中两者中和抗体的发生率较为接近。Kevzara 的专利保护期将持续至 2028 年，不过在此期间预计会受到托珠单抗生物类似药的间接市场侵蚀。

Cluster of Differentiation (CD)-targeted monoclonal antibodies
分化簇(CD)靶向单克隆抗体

• Orencia (abatacept) is a fusion protein targeting CD80/86 to block T cell activation and stands out as the only marketed treatment that does not have a black box warning in its label. Registrational trials demonstrated a 23% placebo-adjusted ACR50 rate at six months, in combination with methotrexate, but the AMPLE study provided head-to-head data showing that Orencia was similarly efficacious to Humira. This comparative study also found fewer serious infections, discontinuations due to adverse events, and less frequent injection site reactions with Orencia, suggesting a better safety profile. The patent protection for Orencia expired in 2022, but very few biosimilars are in development; Kashiv Biosciences announced positive Phase I results for its proposed abatacept biosimilar, KSHB002, in January 2025.
  奥瑞希亚(阿巴西普)是一种靶向 CD80/86 的融合蛋白，通过阻断 T 细胞活化发挥作用，是目前市面上唯一标签中未带有黑框警告的治疗药物。注册试验表明，联合甲氨蝶呤治疗 6 个月时其 ACR50 缓解率较安慰剂组高出 23%，但 AMPLE 研究提供的头对头数据显示奥瑞希亚与修美乐疗效相当。这项对比研究还发现奥瑞希亚严重感染发生率更低、因不良事件导致的停药更少、注射部位反应发生率更低，表明其具有更优的安全性特征。奥瑞希亚的专利保护已于 2022 年到期，但目前仅有极少数生物类似药在研；卡希夫生物科学公司于 2025 年 1 月宣布其阿巴西普生物类似药 KSHB002 的 I 期研究取得积极结果。

• Rituxan (rituximab), an anti-CD20 antibody, scores poorly in our drug assessment model as its label contains a black box warning for fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation and progressive multifocal leukoencephalopathy. The drug does not make up for the safety concerns with efficacy, producing an on-par 22% placebo-adjusted ACR50 rate at 24 weeks in patients on background methotrexate. Moreover, Teva and Celltrion’s Truxima, the first rituximab biosimilar, launched in the US in May 2020, further decreasing this drug’s score from a commercial perspective.
  利妥昔单抗（rituximab）是一种抗 CD20 抗体，在我们的药物评估模型中得分较低，因其说明书包含关于致命性输液相关反应、严重皮肤黏膜反应、乙肝病毒再激活和进行性多灶性脑白质病的黑框警告。该药物未能通过疗效弥补安全性隐患，在使用甲氨蝶呤背景治疗的患者中，24 周时仅取得与安慰剂校正后 22%持平的 ACR50 缓解率。此外，梯瓦制药与赛尔群合作的首个利妥昔单抗生物类似药 Truxima 已于 2020 年 5 月在美国上市，从商业角度进一步降低了该药物的评分。

'I do think patients perhaps don’t like – for instance, if we think about the rituximab scenario where they’re getting successive rounds of infusion, and being given a different [biosimilar] drug each time, I can understand why patients wouldn’t like that.' — UK rheumatology key opinion leader
"我确实认为患者可能不喜欢——例如以利妥昔单抗为例，当他们需要接受连续多轮输液治疗时，每次都被给予不同[生物类似药]品种，我能理解患者为何会对此产生抵触。"——英国风湿病学领域关键意见领袖

Marketed small molecule DMARDs
已上市的小分子 DMARDs

JAK inhibitors  JAK 抑制剂

Based on a September 2021 review of the ORAL SURVEILLANCE study, a large, randomized safety trial evaluating Xeljanz, the FDA announced that JAK inhibitors carry an increased risk of major adverse cardiovascular events (MACE), adding this to the existing boxed warnings for thrombosis, serious infections, and malignancies. Moreover, the therapies were limited to use in patients who have not responded to or cannot tolerate one or more TNF blockers for currently labeled indications, eliminating the potential for first line usage. Then, following the results from the FDA’s review, the EMA’s Pharmacovigilance Risk Assessment Committee published an assessment of this drug class and concluded that these medicines should be used with caution and avoided in patients with existing cardiac risk factors. While many predicted that these safety concerns could bar this class from garnering any substantial market share, the patient and physician desire for convenience and oral administration won out and so, in patients without cardiac risk factors, JAK inhibitors remain a key player in the RA space.
根据 2021 年 9 月对 ORAL SURVEILLANCE 研究（一项评估 Xeljanz 的大型随机安全性试验）的审查结果，美国食品药品监督管理局宣布 JAK 抑制剂会显著增加主要不良心血管事件（MACE）风险，并将此风险与现有关于血栓形成、严重感染和恶性肿瘤的黑框警告并列。此外，该疗法被限制用于对当前适应症中一种或多种 TNF 阻滞剂无反应或不耐受的患者，排除了其作为一线疗法的可能性。随后，欧洲药品管理局药物警戒风险评估委员会根据美国食品药品监督管理局的审查结果，发布了针对此类药物的评估报告，结论认为应谨慎使用这些药物，并避免用于已有心脏风险因素的患者。尽管许多人预测这些安全性问题可能阻碍此类药物获得可观市场份额，但患者和内科医生对用药便利性和口服给药的偏好最终占据上风，因此在无心脏风险因素的患者中，JAK 抑制剂仍是类风湿关节炎治疗领域的重要选择。

• Xeljanz (tofacitinib) is a JAK1/2/3 inhibitor that was the first of its class to reach the market in 2012. Initially, the drug had boxed warnings against malignancy and serious infection, similar to the reigning anti-TNF drugs. However, in 2019, the FDA added warnings for increased risk of blood clots and death used in the higher 10mg twice-daily dosing used in ulcerative colitis, based on interim results from the ORAL SURVEILLANCE study. Although this dosage is not approved for RA, prescribing caution increased, compounded later by the additional warning for MACE in 2021 after Xeljanz failed to show noninferiority on safety endpoints compared to anti-TNFs. Furthermore, consistent with registrational trials, ORAL SURVEILLANCE also demonstrated that efficacy was similar across Xeljanz, Humira, and Enbrel, leaving the JAK inhibitor with little more than the convenience of oral administration to justify usage, although this is the only member of its class that requires twice-daily dosing.
  Xeljanz（托法替尼）是一种 JAK1/2/3 抑制剂，作为该类药物中的首款产品于 2012 年上市。与当时主流的抗 TNF 药物类似，该药最初在说明书中标注了关于恶性肿瘤和严重感染的加框警告。然而 2019 年，基于 ORAL SURVEILLANCE 研究的中期结果，美国食品药品监督管理局针对溃疡性结肠炎患者使用较高剂量（每日两次、每次 10mg）时增加血栓和死亡风险的情况追加了警告。虽然这一剂量未获准用于类风湿关节炎治疗，但处方谨慎度随之提高——2021 年 Xeljanz 在安全性终点未能证明其相对于抗 TNF 药物的非劣效性后，关于主要不良心血管事件的补充警告进一步加剧了这种谨慎。此外，与注册试验结果一致，ORAL SURVEILLANCE 研究也显示 Xeljanz、Humira 和 Enbrel 的疗效相近，这使得这款 JAK 抑制剂仅剩口服给药便利性这一优势来支撑其使用价值，尽管它竟是同类药物中唯一需要每日服用两次的产品。

• Olumiant (baricitinib), a JAK1/2 inhibitor, was the second JAK inhibitor to reach the RA market. Eli Lilly introduced Olumiant at a competitive price, undercutting Xeljanz to encourage uptake. The product has a long patent life, which is expected to be maintained until June 2030 in the US. It may face scant erosion from generic tofacitinib in December 2025, but Xeljanz usage remains low and AbbVie’s Rinvoq will continue to be the primary competitor until generic baricitinib enters the market. Olumiant showed a 20% placebo-adjusted ACR50 rate at week 24 in patients on background DMARDs in registrational trials and results from the RA-BEAM head-to-head trial with Humira demonstrated that it was significantly superior to the TNF-inhibitor at both the 12-week ACR20 and DAS28-CRP endpoints. Additionally, rates of adverse events were similar in RA-BEAM through week 52, although the Olumiant arm had more than twice the number of withdrawals due to adverse events compared to Humira. Another study evaluating adverse events from the FDA’s public reporting system found that out of the three JAK inhibitors approved for RA, Olumiant had the highest proportion of death and cancer-related events while Xeljanz was associated with the most cardiovascular and thrombotic events.
  Olumiant（巴瑞替尼）作为 JAK1/2 抑制剂，是第二个进入类风湿关节炎市场的 JAK 抑制剂。礼来公司以具有竞争力的价格推出该产品，通过低于 Xeljanz 的定价策略促进市场渗透。该药物拥有较长的专利保护期，预计在美国将维持至 2030 年 6 月。虽然可能在 2025 年 12 月面临仿制托法替布的轻微冲击，但 Xeljanz 使用率仍然较低，且艾伯维的 Rinvoq 在仿制巴瑞替尼上市前仍将是其主要竞争对手。在注册试验中，接受背景 DMARDs 治疗的患者第 24 周时 Olumiant 的安慰剂校正 ACR50 应答率达 20%。与修美乐头对头比较的 RA-BEAM 试验结果显示，该药物在第 12 周 ACR20 和 DAS28-CRP 终点均显著优于 TNF 抑制剂。尽管在 52 周内两组不良事件发生率相似，但 Olumiant 组因不良事件导致的退出病例数是修美乐组的两倍以上。 另一项评估食品药品监督管理局公共报告系统中不良事件的研究发现，在三种获批用于类风湿关节炎的 JAK 抑制剂中，奥乐明（Olumiant）的死亡和癌症相关事件比例最高，而尚杰（Xeljanz）则与最多心血管和血栓事件相关。

• Rinvoq (upadacitinib) is one of the most attractive drugs in our assessment model, set apart by its selective JAK1 inhibition, extensive global pivotal trial program, and superiority against AbbVie’s own standard-of-care drug, Humira. As a monotherapy in methotrexate-naïve patients, the drug showed a 27% placebo-adjusted ACR50 at week 24 and, in methotrexate inadequate responders, add-on Rinvoq resulted in an ACR50 rate of 33%, one of the highest efficacies in the RA drug space. Likely in preparation for the looming loss of exclusivity of blockbuster Humira, AbbVie’s randomized, double-blind SELECT-COMPARE trial demonstrated statistical superiority in clinical and functional measures of RA disease activity. This tactic appears to have been successful as Rinvoq usage continues to rise while adalimumab biosimilars chip away at Humira’s market share.
  瑞福乐（乌帕替尼）是我们评估模型中最具吸引力的药物之一，其选择性 JAK1 抑制作用、全球范围的关键临床试验项目以及对艾伯维自身标准治疗药物修美乐的优越疗效使其脱颖而出。作为甲氨蝶呤初治患者的单药治疗，该药物在第 24 周显示出 27%的安慰剂校正 ACR50 缓解率；对于甲氨蝶呤应答不足的患者，联用瑞福乐更实现了 33%的 ACR50 缓解率，这是类风湿关节炎药物领域最高的疗效数据之一。艾伯维可能为应对明星药物修美乐即将面临的专利悬崖，通过随机双盲 SELECT-COMPARE 试验证明了该药在类风湿关节炎疾病活动的临床和功能指标上具有统计学优势。这一策略似乎已见成效——随着阿达木单抗生物类似药不断蚕食修美乐的市场份额，瑞福乐的使用量持续攀升。

• From a safety standpoint, despite being saddled with the class-wide boxed warning for MACE, the SELECT-COMPARE data show that Humira had a higher proportion of adverse events and, in the 1,629 participants, there were five MACE events and four deaths, none of which occurred in the Rinvoq arm. Thromboembolic events were also marginally higher in the Humira patients. Moreover, the study based on the FDA adverse event public database suggested that Rinvoq had the lowest proportion of adverse events compared to Olumiant and Xeljanz, further cementing Rinvoq’s place as a best-in-class JAK inhibitor.
  从安全性角度来看，尽管存在针对 MACE 的类别黑框警告，但 SELECT-COMPARE 数据显示修美乐的不良事件发生率更高——在 1,629 名参与者中出现了 5 例 MACE 事件和 4 例死亡病例，而瑞福组均未发生此类事件。修美乐患者的血栓栓塞事件发生率也略高。此外，基于食品药品监督管理局不良事件公共数据库的研究表明，与巴瑞替尼和托法替尼相比，瑞福的不良事件比例最低，进一步巩固了其作为最佳 JAK 抑制剂的地位。

• Jyseleca (filgotinib), a selective JAK1 inhibitor, has not significantly differentiated itself from other drugs of the same class and has the disadvantage of entering as the fourth-to-market JAK inhibitor. Consequently, the product may be perceived as a “me-too” drug. Moreover, while Rinvoq has demonstrated superiority over Humira, in the FINCH-1 trial, Jyseleca showed only a small ~1.2% improvement on the ACR50 endpoint compared to Humira. Safety issues associated with JAK inhibitors also threaten the drug’s success, despite interviewed KOLs voicing that Jyseleca may have a slight safety advantage over others in its class, with lower VTE rates. Jyseleca is available only in Europe and Japan. Developers Gilead and Galapagos withdrew the drug’s development in the US due to FDA concerns over the benefit/risk profile of the 200mg dose, which demonstrated greater efficacy than the 100mg dose.
  Jyseleca（非戈替尼）作为一种选择性 JAK1 抑制剂，尚未显著区别于同类其他药物，且存在作为第四款上市 JAK 抑制剂的竞争劣势。因此，该产品可能被视为"仿制型"药物。尽管 Rinvoq 已证明优于 Humira，但在 FINCH-1 试验中，Jyseleca 在 ACR50 终点指标上仅比 Humira 提高约 1.2%。尽管受访的权威专家表示 Jyseleca 可能比同类药物具有轻微安全性优势（静脉血栓栓塞率较低），但 JAK 抑制剂相关的安全性问题仍威胁着该药物的市场前景。目前 Jyseleca 仅在欧洲和日本上市。由于美国食品药品监督管理局对 200mg 剂量（相比 100mg 剂量疗效更显著）的获益/风险比存在顾虑，开发商吉利德和 Galapagos 已撤回该药物在美国的上市申请。

'I think the safety issues that have come up are concerning. I will still use the JAK class but likely after failure of TNFs and possibly other biologics. Patients prefer oral and that is an advantage for JAKs.' — US physician
"我认为目前浮现的安全性隐患值得关注。我仍会使用 JAK 抑制剂类药物，但可能仅在 TNF 抑制剂及其他生物制剂治疗失败后使用。患者更倾向口服给药，这是 JAK 类药物的优势所在。"——美国内科医生

Pipeline biologic DMARDs  在研生物制剂类 DMARDs

• AnaptysBio’s rosnilimab is an agonist at the PD-1 receptor expressed preferentially on T cells. This activation reduces T cell overactivity by leveraging the inhibitory impact of PD-1, thus evening out immune responses in RA patients. In the Phase II RENOIR trial, rosnilimab showed notable efficacy and an unusually benign safety profile through week 12, with the 600mg dose achieving a 47% ACR50 response, which grew to 67% by week 14. In comparison to marketed drugs for this indication, both ACR70 and clinical disease activity index low disease activity (CDAI LDA) rates for rosnilimab at the week 14 mark numerically exceed those of Rinvoq, Orencia, and Kevzara at week 24. Although more information is still needed to assess durability and long-term safety, as many of the concerns associated with RA drugs likely take longer than 12 weeks to present, the numerical superiority demonstrated on these endpoints could give rosnilimab the edge if it is equally successful in Phase III.
  AnaptysBio 公司的 rosnilimab 是一种优先在 T 细胞上表达的 PD-1 受体激动剂。这种激活通过利用 PD-1 的抑制作用来降低 T 细胞的过度活跃，从而平衡类风湿关节炎（RA）患者的免疫反应。在 II 期 RENOIR 试验中，rosnilimab 在 12 周内显示出显著的疗效和异常良好的安全性，600mg 剂量组实现了 47%的 ACR50 应答率，到第 14 周时这一数字增长至 67%。与该适应症已上市药物相比，rosnilimab 在第 14 周时的 ACR70 和临床疾病活动指数低疾病活动度（CDAI LDA）率在数值上均超过了 Rinvoq、Orencia 和 Kevzara 在第 24 周时的数据。尽管评估持久性和长期安全性仍需更多信息（因为许多与 RA 药物相关的问题可能需要超过 12 周才会显现），但如果 rosnilimab 在 III 期试验中同样成功，这些终点的数值优势可能使其脱颖而出。

• However, AnaptysBio is also developing rosnilimab for ulcerative colitis (UC), Phase II data for which is expected at the end of 2025. This trial also extends out to a year, which should provide a fuller safety profile, albeit in a different population. Given the small size of the company, AnaptysBio has indicated that it can only support one registrational program at a time, so whether the drug moves to Phase III in 2026 for UC or RA will depend on this next readout.
  然而，AnaptysBio 公司也正在开发用于溃疡性结肠炎(UC)的 rosnilimab，其 II 期数据预计将于 2025 年底公布。这项试验同样持续一年时间，虽然针对不同患者群体，但应能提供更完整的安全性数据。鉴于公司规模较小，AnaptysBio 表示一次只能支持一个注册项目，因此该药物是否会在 2026 年进入 UC 或 RA 的 III 期阶段，将取决于下一次数据读取结果。

Brands will face headwinds as the RA market is penetrated by more biosimilars
随着更多生物类似药进入类风湿关节炎市场，品牌药将面临阻力

The RA market will experience increasing attrition due to biosimilar competition. The EU market has taken the brunt of biosimilar erosion, with earlier launches and more acceptance of biosimilars compared to other regions. Over time, biosimilar penetration is anticipated to gain more momentum as international real-world evidence builds, with long-term data supporting biosimilar efficacy and safety. This should allow physicians and patients to grow their confidence and familiarity with biosimilars, as well as encouraging uptake.
由于生物类似药的竞争，类风湿关节炎市场将经历日益严重的份额流失。欧盟市场首当其冲受到生物类似药冲击，相比其他地区更早上市且对生物类似药接受度更高。随着国际真实世界证据的积累，以及长期数据支持生物类似药的疗效和安全性，预计生物类似药渗透率将加速提升。这将增强医生和患者对生物类似药的信心与熟悉度，并促进其使用。

The anti-TNF class will remain dominant due to physician familiarity and increasing availability of biosimilars
由于内科医生对生物类似药的熟悉度提升及其可获得性增加，抗 TNF 类药物仍将占据主导地位

As multibillion-dollar products, Humira and Enbrel represent the best-selling brands in the market, but since Humira's 2023 patent expiry in the US, 10 adalimumab biosimilars with discounts ranging from 5% to 85% have slowly begun to chip away at the originator brand's stronghold. However, etanercept biosimilars remain held in patent litigation, potentially giving branded Enbrel until 2029 before it could face the same fate as Humira.
作为价值数十亿美元的产品，修美乐和恩利是市场上最畅销的品牌，但自 2023 年修美乐在美国专利到期后，10 款折扣幅度从 5%到 85%不等的阿达木单抗生物类似药已开始逐步侵蚀原研药的市场主导地位。不过，依那西普生物类似药仍受专利诉讼制约，这使得品牌药恩利可能要到 2029 年才会面临与修美乐相同的命运。

Despite safety concerns surrounding the JAK inhibitor class, Rinvoq usage will continue to climb
尽管 JAK 抑制剂类药物存在安全性担忧，但瑞福乐的使用量仍将持续攀升

AbbVie has positioned Rinvoq, a JAK inhibitor approved in 2019, as a follow-on product from Humira. Supported by an extensive global pivotal trial program, as well as data demonstrating Rinvoq’s superiority in head-to-head trials with gold-standard Humira, AbbVie’s experience and presence in the RA market will foster success for the drug, despite its third-to-market status.
艾伯维将 2019 年获批的 JAK 抑制剂瑞福乐（Rinvoq）定位为修美乐的后续产品。凭借全球范围的关键性试验项目支持，以及瑞福乐在头对头试验中优于金标准药物修美乐的数据，艾伯维在类风湿关节炎市场的经验与影响力将助推该药物取得成功，尽管其上市时间位列第三。

While the JAK inhibitors are differentiated by their convenient oral administration, this class has been associated with VTE concerns, which has reined in some of the excitement surrounding the easier route of administration. Although AbbVie released data showing that the rate of VTEs associated with Rinvoq treatment was in line with the background rate for RA patients, the FDA has included a black box warning for all JAK inhibitors. KOLs report that usage is still rising, albeit less so for Xeljanz, which was the drug that provided the impetus for the class-wide safety warning.
虽然 JAK 抑制剂因便捷的口服给药方式形成差异化优势，但该类药物的静脉血栓栓塞风险问题抑制了市场对其便利给药途径的部分热情。尽管艾伯维发布数据显示瑞福乐治疗相关的静脉血栓栓塞发生率与类风湿关节炎患者的基线水平相当，美国食品药品监督管理局仍对所有 JAK 抑制剂加注黑框警告。关键意见领袖指出该类药物的使用率仍在上升，不过因触发全类别安全警告的尚杰（Xeljanz）增长相对缓慢。

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。

Therapies are clinically comparable
各疗法在临床上具有可比性

'Efficacy, I think they are all pretty much in the same ballpark, and some people respond better to one than the other, but I do not think we have anything hard pressed to say that one drug is that much better than another, except that some of them are coming out against adalimumab, and proving that they are doing better than that, but it is small degrees at this point.' — US key opinion leader
"疗效方面，我认为它们基本处于同一水平线。虽然有些患者对某种药物的反应更好，但除了部分新药在与阿达木单抗的对照中显示出轻微优势外，我们尚无确凿证据表明某款药物明显优于其他同类。"——美国关键意见领袖

'[The available therapies] do not majorly differentiate from each other, and part of the reason is that there are not any head-to-head studies. So, apart from the JAKs versus adalimumab, the other studies do not do head-to-head studies, and so I cannot differentiate them, you cannot extrapolate from one study in one unique cohort of patients to another agent, whose study is with a totally different population with different statistical methods of study design.' — EU key opinion leader
"[现有疗法]彼此间并无显著差异，部分原因在于缺乏头对头研究。除了 JAK 抑制剂与阿达木单抗的对比研究外，其他研究都未进行直接比较。因此我们无法区分优劣——不能将针对某特定患者群体的研究结果，简单套用到采用不同研究设计和统计方法、面向完全不同人群的其他药物上。"——欧洲关键意见领袖

'I think really the restrictions are really predicated on cost of goods, and profitability to the insurance company, particularly since most therapies have demonstrated parity on the efficacy side, even though there might be unique safety concerns with each therapy, or for a given patient. In general, safety concerns are not enough to sway an insurance company to allow you to bypass an agent that has a lower cost of goods to move to a more expensive cost of goods.' — US key opinion leader
"我认为这些限制本质上取决于药品成本及保险公司的盈利考量，尤其是当多数疗法在疗效上已显示出相当水平时——尽管每种疗法或特定患者可能存在独特的安全隐患。但总体而言，安全性问题通常不足以促使保险公司允许患者绕过低价药物转而使用更高成本的替代方案。" ——美国关键意见领袖

Pricing and insurance coverage drive prescribing
定价与医保覆盖主导处方选择

'[The most important factor that determines which drug is prescribed] will be insurance! Number one is insurance to make sure they do not have to pay much. So, a lot of insurances have their step edits and requirements, so that is by far number one, and then number two will be mode of administration, whether they want an IV or subcu, or whether we prefer one way, and then number three I think will be the mechanism of action.' — US key opinion leader
"[决定处方药物的最关键因素]绝对是医保！首要条件是确保患者无需承担过高费用。多数保险公司设有阶梯式审核条款和用药要求，这绝对是第一考量；其次是给药方式，取决于患者倾向静脉注射还是皮下注射，或是我们更推荐的途径；第三点我认为是药物作用机制。" ——美国关键意见领袖

'I think we have seen in the United States that the agent that can achieve the best volume discount is the one that often gets on the formulary, and so yes, I think [biosimilars] will steal market share from other members of the class.' — US key opinion leader
"我认为我们在美国已经看到，能够获得最佳批量折扣的药物通常会被列入处方集，所以是的，我认为[生物类似药]将蚕食同类其他药物的市场份额。"——美国关键意见领袖

'In terms of [filgotinib’s] efficacy, again, the FINCH studies are all roughly equitable to the other JAK inhibitor studies. So, there is very little differentiating filgotinib, upadacitinib, tofacitinib, and baricitinib in terms of efficacy or their safety profile, and again, it depends on what Gilead choose in terms of their price point. This will determine how often filgotinib is prescribed.' — EU key opinion leader
"就[非戈替尼]的疗效而言，FINCH 研究与其他 JAK 抑制剂研究基本相当。因此在疗效或安全性方面，非戈替尼、乌帕替尼、托法替尼和巴瑞替尼几乎没有区别，这再次取决于吉利德选择的定价策略，这将决定非戈替尼的处方频率。"——欧盟关键意见领袖

Drugs that help patients achieve remission
帮助患者实现缓解的药物

One major challenge is that current drugs only improve the condition of 60-70% of the population, leaving at least a third of patients without effective treatment. Additionally, only about 50% of patients achieve a 50% improvement, with very few reaching remission. This issue is further complicated by insurance restrictions that prevent the use of the most effective drugs in newly diagnosed patients.
当前面临的主要挑战是：现有药物仅对 60-70%的患者有效，这意味着至少三分之一患者缺乏有效治疗。此外，只有约 50%患者能达到 50%的改善率，实现完全缓解者更是寥寥无几。更复杂的是，保险限制阻碍了新确诊患者使用最有效的药物。

Furthermore, patients often go through multiple lines of biologic therapy without significant improvement, representing a small but major unmet need. Therefore, there is a pressing need for therapies that work better across the population, result in higher levels of efficacy, and approach a greater likelihood of achieving remission.
此外，许多患者经历多轮生物制剂治疗后仍未见显著改善，这虽是小众但却是亟待解决的重要医疗需求。因此，当前亟需能惠及更广泛人群、实现更高疗效水平、并显著提升缓解可能性的治疗方案。

Targeted treatments applied with a stratified medicine approach
采用分层医学策略的靶向治疗

Approximately 30% of patients do not respond to their first biologic therapy, indicating a lack of precision in identifying the appropriate mechanism of action or drug class for each patient. Identifying reliable biomarkers would enable better stratification of patient populations to ensure the delivery of the right drug to the right patient without having to try multiple treatments that turn out to be ineffective.
约 30%患者对首轮生物制剂治疗无应答，这表明在识别适合每位患者的作用机制或药物类别方面仍缺乏精准性。若能确立可靠的生物标志物，将有助于更精准地分层患者群体，确保为特定患者匹配有效药物，避免尝试多种无效治疗方案。

Affordable drugs  可负担药物

The use of specialty drugs has become a significant financial burden on healthcare systems and patients. There is a pressing need for therapies that are both cost-effective and at least as safe as the current therapies, while still providing substantial efficacy.
特种药物的使用已成为医疗系统和患者的重大财务负担。当前亟需兼具成本效益、至少与现有疗法同等安全性，同时仍能提供显著疗效的治疗方案。

Better side effect profiles
更优的副作用表现

Out of the current array of RA drugs, Orencia is the only agent without a boxed warning. The rest of the drugs approved for RA in the US, including the first-line anti-TNFs, have warnings against malignancies and serious infections, as well as MACE and thrombotic events, in the case of the JAK inhibitors.
在现有类风湿关节炎药物中，奥瑞珠单抗是唯一未被加注黑框警告的制剂。美国批准用于类风湿关节炎的其他药物（包括一线抗肿瘤坏死因子制剂）均存在关于恶性肿瘤、严重感染的警示，JAK 抑制剂类药物还额外标注了主要不良心血管事件和血栓事件风险。

Research on safe and effective combinations
安全有效联合疗法的研究

There is inadequate research surrounding which drugs can safely be combined to produce more effective results in patients who have not responded to the standard of care.
关于哪些药物可以安全组合使用以对标准治疗无效的患者产生更佳疗效，目前研究尚不充分。