作者：陈俞钧
美工：何国红 罗真真
排版：马超
01 引言
炎症性肠病 (Inflammatory Bowel Disease, IBD) 是一种慢性且易复发的肠道炎症疾病，主要包括克罗恩病 (Crohn's Disease, CD) 和溃疡性结肠炎 (Ulcerative Colitis, UC) 两种类型 (图1) 。其中，CD可能影响整个消化道，炎症呈跳跃式分布，常导致肠壁全层炎症、增厚、狭窄或瘘管形成，尤其多见于小肠末端；UC则主要局限于结肠和直肠黏膜，炎症连续分布，容易引起黏膜溃疡和出血，以直肠及乙状结肠为主。
▲ 图1. 炎症性肠病：溃疡性结肠炎 (UC) 对比克罗恩病 (CD)
从流行病学角度看，炎症性肠病（IBD）的全球患者总数约达600万例，预计到2030年超700万，到2040年可能超过1000万，受工业化、饮食变化和遗传因素影响，全球年龄标准化发病率约6-8/10万人，患病率100-200/10万人，高收入地区负担重，但新兴地区增速更快。在中国及亚洲，中国患者从1990年的23.9万例增至2019年的91.1万例（近3倍增长），新发病例从1.7万升至3.5万（近2倍），2019年发病率3.01/10万人、患病率47.06/10万人，到2030年预计超150万、2035年达200万以上；亚洲整体从2017年的约57万例预计到2035年超400万，东亚、南亚和东南亚增长显著，如印度发病率从0.2/10万人升至5.6/10万人，日本约5/10万人，韩国约3/10万人，与欧美（0.5%-1.0%）相比虽较低，但增速更快，尤其是儿童发病率年增长5-8%。在其他国家，美国患病率约0.7%（721例/10万人），总患者约200万；加拿大2023年预计825例/10万人，总患者约35万，这些高发区通过早期筛查控制死亡率，但经济负担仍大，整体格局为“西高东低、东快西慢”。
在临床上，IBD症状往往隐匿且多样化，包括持续腹痛（常见于右下腹或脐周）、频繁腹泻（每日数次至数十次）、粪便带血或黏液、体重减轻、疲劳和发热等；严重病例还可能伴随肠外表现，如关节痛、皮肤病变（口疮或红斑结节）、眼部炎症（虹膜炎），而儿童和青少年患者则易影响生长发育，导致身材矮小或骨质疏松。约10-30%的患者初诊时已出现并发症，如肠穿孔或毒性巨结肠，需要紧急手术干预。诊断IBD通常需综合评估，包括详细病史询问、体格检查、实验室指标（如C反应蛋白CRP、红细胞沉降率ESR和粪便钙卫蛋白水平，用于评估炎症活动度）、内镜检查（结肠镜作为金标准，可直观观察黏膜溃疡、假息肉或颗粒样改变）以及影像学（如CT或MRI评估肠壁厚度和并发症）；对于疑难病例，还需排除感染性肠炎、肠结核或贝赫切特病等类似疾病。
随着患者数量的增加，IBD治疗市场规模预计从2025年的221.6亿美元增长至2034年的358.8亿美元，年复合增长率（CAGR）为5.5%，这反映出对新型疗法的迫切需求（图2）。
▲ 图2. 2023-2034 年炎症性肠炎治疗市场规模及展望 (亿美元)
02 IBD的病因与发病机制：免疫失调的“连锁反应”
IBD的病因复杂，涉及遗传、环境、肠道微生物及免疫因素的多重交互作用。多项研究和国际指南指出，遗传因素在易感性中占重要地位——例如，NOD2基因突变显著增加克罗恩病（CD）的风险，而HLA基因变异与溃疡性结肠炎（UC）密切相关。环境因素亦发挥重要作用，包括吸烟（可加重CD但对UC具有一定保护作用）、高脂高糖饮食、感染、心理压力及抗生素暴露等。肠道微生物失调（dysbiosis）被认为是发病机制的核心环节：健康肠道菌群可维持黏膜屏障和免疫稳态，而菌群失衡则可能导致屏障功能破坏，促进病原菌入侵并触发持续炎症反应。
在发病机制上，IBD是由肠道免疫系统对肠道共生菌或抗原的异常反应引起的黏膜免疫过度激活状态。正常情况下，T细胞、B细胞及相关细胞因子维持免疫稳态；而在 IBD 患者中，尤其是克罗恩病，Th1与Th17通路被异常激活，导致TNF-α、IL-12、IL-23、IFN-γ等促炎因子过量释放，引发级联性炎症反应。整合素（如α4β7）介导的白细胞黏附与迁移进一步放大局部免疫损伤。同时，肠上皮屏障功能受损（如紧密连接蛋白减少），促进细菌及其产物跨上皮入侵，形成炎症-屏障破坏-菌群失衡的恶性循环。
03 传统化学药物治疗IBD：弱靶向性暴露的局限与新时代呼唤
传统IBD治疗主要包括氨基水杨酸类药物（如美沙拉嗪）、糖皮质激素（如泼尼松）及免疫调节剂（如硫唑嘌呤）。这类药物能够在一定程度上控制疾病的急性发作，其中5-氨基水杨酸（5-ASA）常用于轻中度溃疡性结肠炎的诱导与维持缓解；糖皮质激素具有快速抗炎作用，但因长期使用可导致骨质疏松、糖尿病和高血压等全身性不良反应而不宜长期应用；免疫调节剂可维持疾病缓解，但疗效因人而异，且存在感染和肿瘤风险。总体而言，约30–50%的克罗恩病患者在病程中仍需手术切除病变肠段，术后复发率较高。由于传统化药作用靶点广泛、特异性较低，难以精准调控炎症信号通路，部分患者出现原发或继发性失应答，疗效有限。单克隆抗体药物的引入有效弥补了这一局限，标志着IBD治疗进入精准靶向时代。
04 抗体药物的革命：精准靶向，重塑IBD治疗格局
传统的广谱免疫抑制向精准靶向调控的转变。这类大分子药物通过单克隆抗体技术，能够特异性识别并结合炎症反应中的关键分子，精确阻断病理性信号通路。目前获批的抗体主要针对TNF-α、整合素、IL-12/23及IL-23等核心靶点（表1）。
▼ 表1. 已上市IBD抗体药物总结（2025年10月）
抗体药物（生物制剂）的出现是炎症性肠病（IBD）治疗领域的里程碑，标志着治疗从与传统非靶向药物（如糖皮质激素或免疫调节剂）相比，抗体药物不仅能显著提高缓解率和黏膜愈合率，还可减少全身性副作用，降低长期用药风险。临床研究显示，应用抗体治疗后患者住院率下降超过30%，生活质量显著改善。至2025年，随着多种新型抗体药物的上市及后期临床研究推进，IBD治疗已全面迈入精准医学时代。
TNF-α（肿瘤坏死因子-α）是最早被确立的核心炎症靶点。TNF-α可激活NF-κB信号通路，诱导促炎细胞因子释放并加速上皮细胞凋亡，从而破坏肠道黏膜屏障，驱动IBD的持续炎症反应。针对该通路开发的TNF-α抑制型抗体，如Infliximab（Remicade）和Adalimumab（Humira），通过高亲和力中和游离及膜结合型TNF-α，有效阻断下游炎症信号，快速缓解症状并促进黏膜愈合（图3）。
▲ 图3. 抗肿瘤坏死因子α (TNF-α) 抗体药物
在炎症性肠病中的治疗作用机制
整合素靶点则聚焦于炎症细胞的迁移，是继TNF-α抑制后IBD治疗的重要方向。整合素是一类介导白细胞黏附与穿越血管内皮的跨膜受体，其中α4β7整合素与肠道血管内皮上的MAdCAM-1特异结合，促进炎症细胞向肠黏膜聚集，从而维持慢性炎症反应。整合素抑制型抗体通过阻断这一关键黏附过程，可实现肠道选择性免疫调控，显著减少全身免疫抑制带来的感染风险。代表药物Vedolizumab（Entyvio）专一拮抗α4β7整合素，已广泛用于克罗恩病和溃疡性结肠炎，表现出良好的疗效与安全性。另一种药物Natalizumab（Tysabri）靶向α4整合素，虽能有效控制炎症，但因可能引发进行性多灶性白质脑病（PML）而限制了使用范围（图4）。
▲ 图4. 整合素抗体药物及其靶点
在炎症性肠病中的总结 (Gubatan et al)
IL-12/23通路是调控Th1与Th17细胞分化的关键环节，构成炎症性肠病（IBD）免疫反应的重要枢纽。IL-12促进Th1细胞分化并诱导干扰素γ（IFN-γ）释放，驱动细胞免疫反应；而IL-23维持Th17细胞活化，促进IL-17和IL-22的分泌，加剧肠黏膜炎症。基于此，靶向该通路的抗体药物通过精准阻断炎症信号，为中重度IBD治疗提供了新策略。Ustekinumab（Stelara）是首个靶向IL-12/23共同p40亚基的抗体，可同时抑制Th1和Th17介导的炎症反应，显著改善克罗恩病和溃疡性结肠炎的临床结局。随后发展的Risankizumab（Skyrizi）与Mirikizumab（Omvoh）专一靶向IL-23的p19亚基，能有效抑制Th17驱动的炎症，同时避免IL-12抑制所带来的感染风险（图5）。
▲ 图5. 白介素 (IL) -23和IL-12抗体药物
在炎症性肠病中的作用机制
另外在已获批的成熟IBD抗体药物基础上，也有多款新兴抗体正处于临床试验中，旨在针对难治性患者提供创新解决方案。关键类别包括TL1A抑制剂（图6），如Tulisokibart（Merck，3期，UC/CD）、Duvakitug（Sanofi/Teva，3期，UC/CD）和Afimkibart（Roivant/Pfizer，3期UC/2期CD），旨在抑制炎症和纤维化；其他创新如OSE-127（IL-7Rα，Ose Immuno，2/3期，UC），通过新型机制调控免疫（表2）。
▲ 图6. TL1A 调控炎症和纤维化的分子机制
▼表2. 临床中IBD抗体药物总结 (2025年10月)
05 新型靶向型小分子药物的应用与优势
随着精准医学的发展，单克隆抗体等生物制剂的应用标志着IBD治疗进入靶向化时代。与此并行，新型小分子药物作为口服靶向疗法，正逐渐成为治疗IBD的重要补充（表3）。这类药物分子量小、生物利用度高、口服方便，可快速抑制特定炎症信号通路（如JAK/STAT或S1P途径）。与抗体生物制剂相比，小分子药物生产成本更低、使用更简便，但仍需监测肝肾功能及感染风险。它们主要用于中重度IBD患者，尤其适用于对生物制剂反应不足或失应的患者。临床试验显示，小分子药物的诱导缓解率约20–40%（针对中重度患者）。
▼ 表3. 已获批用于IBD的小分子药物总结 (2025年10月)
06 2025年最新进展：IBD抗体治疗的未来前沿
在靶点创新不断推进的同时，随着炎症性肠病（IBD）患者对传统疗法的耐药性和依从性问题日益凸显，2025年IBD治疗领域正加速转向多维度探索，包括双特异性抗体（双抗）的多靶点协同作用、长效制剂的半衰期优化以减少给药频率，以及口服递送系统的开发以提升患者便利性和生物利用度。这些新兴策略不仅旨在提高疗效和安全性，还能针对生物难治性病例提供个性化方案，推动IBD从慢性管理向治愈性治疗转型，预计将重塑全球市场格局。
双特异性抗体作为新一代疗法，展现巨大潜力，能同时针对多个炎症通路，提高疗效并减少抗药性。例如HXN1002实验性双特异性抗体（α4β7 x TL1A）体外和动物模型研究结果积极，2025年4月Sanofi获得HXN1002的全球许可，用于溃疡性结肠炎和克罗恩病开发；Sor102等探索TNF-α与IL-23联合靶向，临床试验显示更高缓解率；Xencor提出TL1A与CD3 T细胞接合双特异性抗体组合，用于IBD协同治疗。这些进展表明，双抗可能成为IBD精准疗法的下一个里程碑。
此外，Spyre Therapeutics通过YTE工程化改造优化Fc区，延长半衰期至典型抗体的约3倍以上。其α4β7抗体SPY001（Phase 1/2）在人体PK中估计半衰期>90天，TL1A抗体SPY002（Phase 1）估计半衰期约75天。两者安全性良好，且 PK 数据支持每季度或每半年一次给药。公司还计划扩展其IL-23靶标项目（SPY003），以推动IBD的慢性管理向更高效、更少给药次数方向发展。
在纳米口服抗体方面，2025年突破（Hussack G et al., 2025）报道了一种工程化蛋白酶稳定的口服单域抗体，用于抑制IL-23信号通路，针对炎症性肠病治疗，该技术启用口服递送，推动从注射向口服转型，预计未来进入临床试验。
此外，PRX-106是由Protalix BioTherapeutics开发的口服重组TNF融合蛋白，用于IBD治疗，通过植物细胞表达TNFRII-Fc实现口服递送TNF抑制剂，早期临床试验显示抗炎效果和安全性良好，有潜力降低系统副作用并提高患者依从性。此外外泌体疗法或成为炎症性肠病（IBD）治疗的新方向，可通过局部递送抗炎因子修复肠道屏障、减少系统副作用。2024–2025年间，多家初创公司如EXO Biologics（A轮融资1600万欧元）与EVerZom（融资1000万欧元开发EVerGel）推动该领域加速迈向临床与多模态组合疗法。
07 结语：行动起来，共筑健康防线
炎症性肠病（IBD）作为一种慢性顽疾，长期困扰着无数患者，但随着抗体大分子靶向药物的快速发展，我们看到了曙光。这些精准疗法不仅有效缓解症状，还显著降低并发症风险，提高生活质量。从TNF-α抑制剂到新兴TL1A等抗体靶向药物，再到双特异性抗体和口服抗体的推进，2025年之后的IBD治疗正迈向多维精准时代。临床数据显示，早用生物制剂可将住院率降低30%以上，未来新药物的加入或将进一步革新治疗格局。作为患者或家属，及早筛查至关重要：定期体检、监测症状、咨询专业医师，选择适合的抗体药物方案，能有效控制疾病进展。同时，保持健康饮食、避免吸烟、减轻压力，也有助于预防复发。让我们共同行动起来，传播科普知识，支持生物医药创新，一起守护肠道健康，拥抱无炎症的美好生活！
Sanyou 10th Anniversary: A Revolution in IBD Treatment: How Antibody Drugs Pinpoint Inflammation with Precision?
01 Introduction
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation of the digestive tract, mainly including Crohn’s disease (CD) and ulcerative colitis (UC) (Figure 1). CD can affect any part of the gastrointestinal tract, often in a patchy, “skip” pattern, leading to full-thickness inflammation, intestinal wall thickening, strictures, or fistulas—most commonly in the terminal ileum. In contrast, UC is limited to the mucosal layer of the colon and rectum, with continuous inflammation that often causes ulcers and bleeding, typically starting from the rectum and extending to the sigmoid colon.
▲ Figure 1. Inflammatory Bowel Disease: Comparison of Ulcerative Colitis (UC) and Crohn’s Disease (CD)
From an epidemiological perspective, inflammatory bowel disease (IBD) affects about 6 million people worldwide, projected to exceed 7 million by 2030 and 10 million by 2040. Industrialization, dietary changes, and genetic factors drive its rise, with a global age-standardized incidence of around 6–8 cases per 100,000 and prevalence of 100–200 per 100,000. While high-income regions bear the greatest burden, new cases are increasing faster in emerging areas. In China, patient numbers surged from 239,000 in 1990 to 911,000 in 2019—nearly a threefold rise—with new cases doubling to 35,000 annually. By 2030, China’s total cases may exceed 1.5 million and reach over 2 million by 2035. Across Asia, cases are expected to climb from about 570,000 in 2017 to over 4 million by 2035, with rapid growth in East, South, and Southeast Asia—India’s incidence jumped from 0.2 to 5.6 per 100,000, Japan reports about 5, and South Korea about 3. Though rates remain lower than Western countries (0.5–1.0%), Asia’s growth is faster, especially among children, rising 5–8% annually. In comparison, the U.S. has a prevalence of about 0.7% (721 per 100,000; ~2 million patients), and Canada around 825 per 100,000 (~350,000 patients). Early screening helps control mortality in these high-incidence areas, but economic burdens remain significant, forming a global pattern of “high in the West, rising fast in the East.”
Clinically, the symptoms of inflammatory bowel disease (IBD) are often subtle and varied, including persistent abdominal pain (commonly in the lower right or around the navel), frequent diarrhea (ranging from several to dozens of times per day), blood or mucus in stool, weight loss, fatigue, and fever. Severe cases may also present with extraintestinal manifestations such as joint pain, skin lesions (like mouth ulcers or erythema nodosum), and eye inflammation (iritis). In children and adolescents, IBD can impair growth and bone health, leading to short stature or osteoporosis. About 10–30% of patients are diagnosed only after complications such as intestinal perforation or toxic megacolon occur, requiring emergency surgery. Diagnosis typically involves a comprehensive evaluation—medical history, physical examination, lab tests (including C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and fecal calprotectin to assess inflammation), endoscopy (colonoscopy remains the gold standard to visualize ulcers, pseudopolyps, or granular mucosa), and imaging (CT or MRI to assess bowel wall thickening and complications). For challenging cases, it’s crucial to rule out similar conditions like infectious colitis, intestinal tuberculosis, or Behçet’s disease.
With the rising number of patients, the global market for inflammatory bowel disease (IBD) treatments is projected to grow from USD 22.16 billion in 2025 to USD 35.88 billion by 2034, at a compound annual growth rate (CAGR) of 5.5%. This steady expansion highlights the urgent demand for novel and more effective therapies (Figure 2).
▲ Figure 2. Inflammatory Bowel Disease Treatment Market Size and Outlook (USD Billion), 2023-2034
02 Etiology and Pathogenesis of IBD: The “Chain Reaction” of Immune Dysregulation
The causes of inflammatory bowel disease (IBD) are complex, involving interactions among genetic, environmental, microbial, and immune factors. Studies and international guidelines highlight genetics as a key contributor—mutations in the NOD2 gene significantly increase the risk of Crohn’s disease (CD), while variations in HLA genes are closely linked to ulcerative colitis (UC). Environmental influences also play a major role, including smoking (which worsens CD but may offer some protection against UC), high-fat and high-sugar diets, infections, psychological stress, and antibiotic exposure. Gut microbiota imbalance (dysbiosis) is considered central to IBD pathogenesis: a healthy microbiome helps maintain the intestinal barrier and immune balance, whereas disruption of this ecosystem can impair barrier integrity, allow harmful bacteria to invade, and trigger chronic inflammation.
In terms of disease mechanisms, inflammatory bowel disease (IBD) results from an abnormal immune reaction to gut microbes or antigens, causing excessive activation of the intestinal mucosal immune system. Normally, T cells, B cells, and cytokines maintain immune balance, but in IBD—especially Crohn’s disease—the Th1 and Th17 pathways become overactive, releasing high levels of pro-inflammatory molecules such as TNF-α, IL-12, IL-23, and IFN-γ and driving a cascade of inflammation. Integrins (e.g., α4β7) promote white blood cell adhesion and migration, worsening tissue damage. At the same time, the intestinal barrier becomes weakened—such as through reduced tight junction proteins—allowing bacteria and their products to cross the gut lining, creating a vicious cycle of inflammation, barrier breakdown, and microbiome imbalance.
03 Traditional Chemical Therapies for IBD: The Limitations of Weak Targeting and the Call for a New Era
Traditional treatments for IBD mainly include aminosalicylates (e.g., mesalamine), corticosteroids (e.g., prednisone), and immunomodulators (e.g., azathioprine). These drugs help control acute flare-ups to varying degrees. Among them, 5-aminosalicylic acid (5-ASA) is commonly used to induce and maintain remission in mild to moderate ulcerative colitis. Corticosteroids act rapidly to suppress inflammation but are unsuitable for long-term use due to systemic side effects such as osteoporosis, diabetes, and hypertension. Immunomodulators can help sustain remission, though their efficacy varies among individuals and carries risks of infection and malignancy. Overall, about 30–50% of Crohn’s disease patients still require surgical removal of diseased intestinal segments, with a high risk of postoperative relapse. Because traditional chemical drugs act on broad, non-specific targets and cannot precisely regulate inflammatory signaling pathways, some patients experience primary or secondary loss of response. The introduction of monoclonal antibody therapies has addressed these limitations, ushering IBD treatment into a new era of precision targeting.
04 The Antibody Revolution: Precision Targeting Reshaping the Landscape of IBD Treatment
The shift from broad-spectrum immunosuppression to precise, targeted regulation marks a major advance in IBD therapy. These large-molecule drugs, developed through monoclonal antibody technology, can specifically recognize and bind key molecules involved in inflammation, precisely blocking pathological signaling pathways. Currently approved antibodies mainly target core molecules such as TNF-α, integrins, IL-12/23, and IL-23 (see Table 1).
▼ Table 1. Summary of Approved Antibody Therapies for IBD (as of October 2025)
The advent of antibody-based biologics has been a milestone in the treatment of IBD, marking a shift from traditional non-targeted therapies such as corticosteroids and immunomodulators. Unlike these older drugs, antibody therapies can significantly improve remission rates and promote mucosal healing while reducing systemic side effects and long-term medication risks. Clinical studies show that biologic treatment can lower hospitalization rates by more than 30% and greatly enhance patients’ quality of life. By 2025, with the introduction of multiple new antibody drugs and continued progress in late-stage clinical trials, IBD therapy has fully entered the era of precision medicine.
TNF-α (tumor necrosis factor-α) was the first key inflammatory target identified in IBD. This molecule activates the NF-κB pathway, triggers the release of pro-inflammatory cytokines, and accelerates epithelial cell death, leading to breakdown of the intestinal barrier and persistent inflammation. Antibodies designed to block this pathway—such as infliximab (Remicade) and adalimumab (Humira)—bind TNF-α with high affinity in both its soluble and membrane-bound forms, effectively shutting down downstream inflammatory signals. As a result, they can rapidly relieve symptoms and promote mucosal healing (Figure 3).
▲ Figure 3. Mechanism of Action of Anti TNF-αAntibody Therapies in IBD
The integrin target focuses on the migration of inflammatory cells, marking a key direction in IBD treatment after TNF-α inhibition. Integrins are transmembrane receptors that mediate leukocyte adhesion and transmigration through blood vessel endothelium. The α4β7 integrin specifically binds to MAdCAM-1 on intestinal endothelial cells, promoting the accumulation of inflammatory cells in the intestinal mucosa, thus maintaining chronic inflammation. Integrin inhibitors block this crucial adhesion process, allowing selective immune regulation in the gut and significantly reducing the infection risk associated with systemic immunosuppression. The representative drug Vedolizumab (Entyvio) specifically antagonizes α4β7 integrin and has been widely used for Crohn’s disease and ulcerative colitis, showing good efficacy and safety. Another drug, Natalizumab (Tysabri), targets α4 integrin and effectively controls inflammation but is restricted due to the potential risk of progressive multifocal leukoencephalopathy (PML) (Figure 4).
▲ Figure 4. Summary of Integrin Antibody Therapies and Their Targets in IBD (Gubatan et al.)
The IL-12/23 pathway plays a central role in regulating the differentiation of Th1 and Th17 cells, serving as a key hub in the immune response underlying IBD. IL-12 promotes Th1 differentiation and triggers interferon-γ (IFN-γ) release, driving cellular immune responses, while IL-23 sustains Th17 activation and stimulates IL-17 and IL-22 secretion, amplifying intestinal inflammation. Targeting this pathway offers a new strategy for treating moderate-to-severe IBD by precisely blocking inflammatory signaling. Ustekinumab (Stelara), the first antibody to target the shared p40 subunit of IL-12 and IL-23, suppresses both Th1- and Th17-mediated inflammation, significantly improving outcomes in Crohn’s disease and ulcerative colitis. Newer agents such as Risankizumab (Skyrizi) and Mirikizumab (Omvoh) selectively block the IL-23 p19 subunit, effectively inhibiting Th17-driven inflammation while minimizing infection risks associated with IL-12 suppression (Figure 5).
▲ Figure 5. Mechanisms of Action of Interleukin (IL)-23 and IL-12 Antibody Therapies in IBD
Building on the foundation of approved antibody therapies for IBD, several next-generation antibodies are now in clinical trials, aiming to provide innovative options for treatment-resistant patients. Key categories include TL1A inhibitors (Figure 6)—such as Tulisokibart (Merck; Phase 3, UC/CD), Duvakitug (Sanofi/Teva; Phase 3, UC/CD), and Afimkibart (Roivant/Pfizer; Phase 3 UC / Phase 2 CD)—which target both inflammation and fibrosis. Other novel approaches include OSE-127 (IL-7Rα antibody, Ose Immuno; Phase 2/3, UC), which modulates immune responses through a new mechanism of action (Table 2).
▲ Figure 6. Molecular Mechanisms of TL1A in Regulating Inflammation and Fibrosis
▼Table 2. Summary of Antibody Therapies for IBD in Clinical Development (October 2025)
05 Application and Advantages of Novel Targeted Small-Molecule Drugs
With the advancement of precision medicine, the use of biologic agents such as monoclonal antibodies marks the era of targeted therapy for IBD. Alongside this, novel small-molecule drugs, as oral targeted therapies, are gradually becoming an important complement in the treatment of IBD (Table 3). These drugs have a small molecular size, high bioavailability, and are easy to administer orally. They can quickly inhibit specific inflammatory signaling pathways (e.g., JAK/STAT or S1P pathways). Compared to antibodies, small-molecule drugs are more cost-effective and simpler to use, although monitoring liver and kidney function, as well as infection risks, is still necessary. They are primarily used in moderate-to-severe IBD patients, particularly those who have insufficient response to or loss of response to biologics. Clinical trials show that the induction remission rate for small-molecule drugs is around 20-40% in moderate-to-severe patients.
▼ Table 3. Summary of Approved Small-Molecule Drugs for IBD (October 2025)
06 Latest Advances in 2025: The Future Frontiers of Antibody Therapy for IBD
As innovation in therapeutic targets continues to advance, the growing challenges of drug resistance and poor adherence among patients with IBD are driving a multidimensional shift in treatment strategies by 2025. Emerging approaches include bispecific antibodies with multi-target synergy, long-acting formulations optimized for extended half-life and reduced dosing frequency, and oral delivery systems designed to improve convenience and bioavailability. These strategies aim not only to enhance efficacy and safety but also to offer personalized options for biologic-refractory cases—accelerating the transformation of IBD therapy from chronic management toward potential cure and reshaping the global treatment landscape.
Bispecific antibodies, as a new generation of therapy, show great potential by simultaneously targeting multiple inflammatory pathways to enhance efficacy and reduce drug resistance. For example, the experimental bispecific antibody HXN1002 (α4β7 × TL1A) has demonstrated promising results in vitro and in animal models, leading Sanofi to obtain global licensing rights in April 2025 for its development in ulcerative colitis and Crohn’s disease. Other candidates, such as Sor102, are exploring dual targeting of TNF-α and IL-23, with clinical trials showing higher remission rates. Meanwhile, Xencor has proposed a TL1A–CD3 bispecific antibody combination for synergistic IBD therapy. These advances suggest that bispecific antibodies may become the next milestone in precision treatment for IBD.
In addition, Spyre Therapeutics has optimized the Fc region through YTE engineering, extending antibody half-life to more than three times that of typical antibodies. Its α4β7 antibody SPY001 (Phase 1/2) showed an estimated half-life of over 90 days in human PK studies, while the TL1A antibody SPY002 (Phase 1) demonstrated an estimated half-life of around 75 days. Both candidates exhibited good safety profiles, with PK data supporting quarterly or biannual dosing. The company also plans to expand its IL-23–targeted program (SPY003) to advance IBD management toward more efficient and less frequent treatment regimens.
In the field of oral nanobodies, a 2025 breakthrough (Hussack G et al., 2025) reported an engineered protease-stable oral single-domain antibody designed to inhibit the IL-23 signaling pathway for the treatment of IBD. This technology enables oral delivery, marking a shift from injectable to oral therapies, and is expected to enter clinical trials in the future.
In addition, PRX-106, developed by Protalix BioTherapeutics, is an oral recombinant TNF fusion protein for IBD treatment. It uses plant cells to express TNFRII-Fc, enabling oral delivery of a TNF inhibitor. Early clinical studies have shown good anti-inflammatory effects and safety, with potential to reduce systemic side effects and improve patient compliance. Meanwhile, exosome therapy may become a new direction for treatment in IBD. By delivering anti-inflammatory factors locally, it can help repair the intestinal barrier while minimizing systemic toxicity. From 2024 to 2025, several startups—such as EXO Biologics (Series A funding €16 million) and EVerZom (raised €10 million to develop EVerGel)—have accelerated clinical translation and multimodal combination strategies in this field.
07 Conclusion: Take Action Together to Build a Stronger Health Defense
Inflammatory bowel disease (IBD), a chronic and persistent disorder, has long troubled countless patients—but with the rapid progress of antibody-based targeted therapies, a new dawn is emerging. These precision treatments not only relieve symptoms effectively but also reduce complications and improve quality of life. From TNF-α inhibitors to novel TL1A-targeting antibodies, and from bispecific to oral antibody therapies, IBD treatment is entering a new era of multidimensional precision beyond 2025. Clinical studies show that early use of biologics can lower hospitalization rates by over 30%, and new drugs in development may further revolutionize treatment strategies. For patients and families, early screening is crucial—regular checkups, symptom monitoring, and consulting healthcare professionals to select suitable antibody therapies can effectively control disease progression. At the same time, maintaining a healthy diet, avoiding smoking, and managing stress help prevent relapse. Let’s work together to spread scientific awareness, support biopharmaceutical innovation, and protect gut health—embracing a future free from inflammation.
▶ Reference
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