骨关节炎免疫治疗及新型技术研究进展

doi:10.12092/j.issn.1009-2501.2026.09.015

摘要/Abstract

摘要：

骨关节炎（osteoarthritis，OA）是一种以关节疼痛、功能障碍和软骨退变为主要特征的慢性疾病，目前仍缺乏能够有效改变其疾病进程的治疗手段。近年来，随着免疫学、分子生物学及干细胞与基因工程技术的进展，OA的治疗研究不断推进。特异性靶向药物与非特异性抗炎药物在部分临床试验中表现出一定的抗炎或镇痛作用，但整体疗效有限且存在安全性顾虑。与此同时，免疫治疗、细胞治疗和基因治疗等新型技术为OA干预提供了新的思路，并在抑制炎症、保护软骨及改善疼痛方面显示出潜在优势，但其长期安全性、疗效稳定性及患者分层策略仍需进一步明确。未来，OA的治疗有望向精准分型、联合干预、局部长效免疫调节以及新型药物递送方向发展。本综述总结了相关研究进展，为未来OA治疗策略优化提供参考。

关键词: 骨关节炎, 免疫治疗, 细胞与基因治疗, 临床试验

Abstract:

Osteoarthritis (OA) is a chronic condition characterized by joint pain, functional impairment, and degeneration of articular cartilage. Currently, there remains a lack of effective treatments capable of altering the disease progression. In recent years, advances in immunology, molecular biology, stem cell technology, and genetic engineering have driven forward research on OA therapies. Although targeted agents and non-specific anti-inflammatory drugs have shown certain anti-inflammatory or analgesic effects in some clinical trials, their overall efficacy remains limited and safety concerns persist. Meanwhile, emerging approaches such as immunotherapy, cell-based therapy, and gene therapy offer novel strategies for OA intervention, showing potential advantages in suppressing inflammation, preserving cartilage, and alleviating pain. However, issues such as long-term safety, durability of therapeutic effects, and patient stratification require further clarification. In the future, OA treatment is expected to evolve toward precise phenotyping, combined interventions, localized long-term immunomodulation, and innovative drug delivery approaches. This review summarizes recent advances in the field to provide insights for optimizing future therapeutic strategies for OA.

Key words: osteoarthritis, immunotherapy, cell and gene therapy, clinical trials

中图分类号:

R684.3

高自顺, 李云霞. 骨关节炎免疫治疗及新型技术研究进展[J]. 中国临床药理学与治疗学, 2026, 31(9): 1286-1296.

Zishun GAO, Yunxia LI. Research progress in immunotherapy and emerging technologies for osteoarthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(9): 1286-1296.

图/表 3

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药物名称	靶点/作用	目的	受试者情况	给药方案	随访时间	试验结果	试验编号/文献编号
阿达木单抗	TNF	评估在侵蚀性HOA患者疗效	43人，18治疗，25安慰剂	40 mg，皮下注射，间隔14 d	3个月	无缓解疼痛	ACTRN12612000791831^[9]
阿达木单抗	TNF	评估在疼痛性HOA患者疗效	85人，41治疗，37安慰剂组	40 mg，皮下注射，间隔15 d	6个月	无缓解疼痛	NCT00597623^[10]
依那西普	TNF-α	评估在侵蚀性HOA患者疗效	90人，45治疗，45安慰剂组	50 mg，皮下注射，间隔7 d	6个月	无缓解疼痛	NTR1192^[14]
鲁吉珠单抗	IL-1α/β	评估在侵蚀性HOA患者中的疗效、安全性	110人，49治疗，61安慰剂组	200 mg，皮下注射，间隔14 d	6个月	无缓解疼痛	NCT02384538^[21]
鲁吉珠单抗	IL-1α/β	评价在伴有滑膜炎的KOA患者中的疗效	347人，随机分配治疗组和安慰剂组	25、100或200 mg组，皮下注射，间隔14 d	13个月	无缓解疼痛和抗炎效果	NCT02087904^[22]
卡那单抗	IL-1β	评估全髋关节或全膝关节置换术的发生率	10 061人，随机分配治疗组和安慰剂组	50、150或300 mg，皮下注射，间隔3个月	3.7年	置换率降低	NCT01327846^[28]
托珠单抗	IL-6	评价在HOA患者中的疗效	91人，45治疗，46安慰剂组	8 mg/kg，静脉注射，间隔4周	3个月	无缓解疼痛	NCT02477059^[31]
奥替利单抗	GM-CSF	评价在HOA患者中的疗效、安全性	44人，22治疗，22安慰剂组	180 mg，皮下注射，间隔1个月	10周	无缓解疼痛	NCT02683785^[34]
地诺单抗	RANKL	评估在侵蚀性HOA患者结构修饰的影响	100人，51治疗，49安慰剂组	60 mg，皮下注射，间隔3个月	48周	具有结构修饰作用	2015-003223-53^[39]
他尼珠单抗	NGF	评价在KOA患者安全性和镇痛功效	450人，每组75治疗，75安慰剂组	10、25、50、100或200 μg/kg，静脉注射，间隔 56 d	16周	疼痛减轻和功能改善	NCT00394563^[41]
他尼珠单抗	NGF	评价在OA患者中的疗效	4541人，4027治疗，514安慰剂组	2.5、5 mg，皮下注射，间隔16周/ 24周	24周	缓解疼痛	NCT02697773 NCT02709486 NCT02528188^[42-43]
甲氨蝶呤	抗炎	评估HOA患者疼痛和结构进展的影响	64人，32治疗，32安慰剂组	10 mg，口服，间隔1周	12个月	无缓解疼痛	NCT01068405^[44]
甲氨蝶呤	抗炎	评估在对KOA患者的症状益处	155人，77治疗，78安慰剂组	10、25 mg，口服，间隔1周	6个月	缓解疼痛、僵硬和功能减轻	ISRCTN77854383^[45]
甲氨蝶呤	抗炎	评估在对KOA患者的症状益处	215人，108治疗，107安慰剂组	15 mg，口服，间隔1周	52周	无缓解疼痛	NCT03815448^[46]
泼尼松龙	抗炎	评价在KOA患者的疗效和安全性	92人，46治疗，46安慰剂组	10 mg，口服，每天1次	6周	缓解疼痛	NTR5263^[49]
秋水仙碱	抗炎	评价在HOA患者的疗效和安全性	100人，50治疗，50安慰剂组	0.5 mg，口服，每天2次	12 周	无缓解疼痛	NCT04601883^[52]
秋水仙碱	抗炎	评价是否能降低全膝关节置换术和全髋关节置换术的发生率	5 522人， 2 762名治疗，2 760安慰剂组	0.5 mg，口服，每天1次	3/6个月	较低发生率	ACTRN12614000093684^[53]
羟氯喹	抗炎	评估对KOA患者疼痛和活动能力方面的疗效	166人，83名治疗，83安慰剂组	400 mg, 口服，每天1次	36 周	缓解疼痛	DOI: https://doi.org/10.3904/kjim.2021.524^[55]
		评估对HOA患者症状的改善效果	196人，98名治疗，98安慰剂组	400 mg口服，每天1次	24周	无缓解疼痛	NCT01148043^[56]
		评估对HOA患者的镇痛效果	210人，105名治疗，105安慰剂组	200至400 mg, 口服，每天1次	12月	无缓解疼痛	ISRCTN91859104^[57]

药物名称	靶点/作用	目的	受试者情况	给药方案	随访时间	试验结果	试验编号/文献编号
阿达木单抗	TNF	评估在侵蚀性HOA患者疗效	43人，18治疗，25安慰剂	40 mg，皮下注射，间隔14 d	3个月	无缓解疼痛	ACTRN12612000791831^[9]
阿达木单抗	TNF	评估在疼痛性HOA患者疗效	85人，41治疗，37安慰剂组	40 mg，皮下注射，间隔15 d	6个月	无缓解疼痛	NCT00597623^[10]
依那西普	TNF-α	评估在侵蚀性HOA患者疗效	90人，45治疗，45安慰剂组	50 mg，皮下注射，间隔7 d	6个月	无缓解疼痛	NTR1192^[14]
鲁吉珠单抗	IL-1α/β	评估在侵蚀性HOA患者中的疗效、安全性	110人，49治疗，61安慰剂组	200 mg，皮下注射，间隔14 d	6个月	无缓解疼痛	NCT02384538^[21]
鲁吉珠单抗	IL-1α/β	评价在伴有滑膜炎的KOA患者中的疗效	347人，随机分配治疗组和安慰剂组	25、100或200 mg组，皮下注射，间隔14 d	13个月	无缓解疼痛和抗炎效果	NCT02087904^[22]
卡那单抗	IL-1β	评估全髋关节或全膝关节置换术的发生率	10 061人，随机分配治疗组和安慰剂组	50、150或300 mg，皮下注射，间隔3个月	3.7年	置换率降低	NCT01327846^[28]
托珠单抗	IL-6	评价在HOA患者中的疗效	91人，45治疗，46安慰剂组	8 mg/kg，静脉注射，间隔4周	3个月	无缓解疼痛	NCT02477059^[31]
奥替利单抗	GM-CSF	评价在HOA患者中的疗效、安全性	44人，22治疗，22安慰剂组	180 mg，皮下注射，间隔1个月	10周	无缓解疼痛	NCT02683785^[34]
地诺单抗	RANKL	评估在侵蚀性HOA患者结构修饰的影响	100人，51治疗，49安慰剂组	60 mg，皮下注射，间隔3个月	48周	具有结构修饰作用	2015-003223-53^[39]
他尼珠单抗	NGF	评价在KOA患者安全性和镇痛功效	450人，每组75治疗，75安慰剂组	10、25、50、100或200 μg/kg，静脉注射，间隔 56 d	16周	疼痛减轻和功能改善	NCT00394563^[41]
他尼珠单抗	NGF	评价在OA患者中的疗效	4541人，4027治疗，514安慰剂组	2.5、5 mg，皮下注射，间隔16周/ 24周	24周	缓解疼痛	NCT02697773 NCT02709486 NCT02528188^[42-43]
甲氨蝶呤	抗炎	评估HOA患者疼痛和结构进展的影响	64人，32治疗，32安慰剂组	10 mg，口服，间隔1周	12个月	无缓解疼痛	NCT01068405^[44]
甲氨蝶呤	抗炎	评估在对KOA患者的症状益处	155人，77治疗，78安慰剂组	10、25 mg，口服，间隔1周	6个月	缓解疼痛、僵硬和功能减轻	ISRCTN77854383^[45]
甲氨蝶呤	抗炎	评估在对KOA患者的症状益处	215人，108治疗，107安慰剂组	15 mg，口服，间隔1周	52周	无缓解疼痛	NCT03815448^[46]
泼尼松龙	抗炎	评价在KOA患者的疗效和安全性	92人，46治疗，46安慰剂组	10 mg，口服，每天1次	6周	缓解疼痛	NTR5263^[49]
秋水仙碱	抗炎	评价在HOA患者的疗效和安全性	100人，50治疗，50安慰剂组	0.5 mg，口服，每天2次	12 周	无缓解疼痛	NCT04601883^[52]
秋水仙碱	抗炎	评价是否能降低全膝关节置换术和全髋关节置换术的发生率	5 522人， 2 762名治疗，2 760安慰剂组	0.5 mg，口服，每天1次	3/6个月	较低发生率	ACTRN12614000093684^[53]
羟氯喹	抗炎	评估对KOA患者疼痛和活动能力方面的疗效	166人，83名治疗，83安慰剂组	400 mg, 口服，每天1次	36 周	缓解疼痛	DOI: https://doi.org/10.3904/kjim.2021.524^[55]
		评估对HOA患者症状的改善效果	196人，98名治疗，98安慰剂组	400 mg口服，每天1次	24周	无缓解疼痛	NCT01148043^[56]
		评估对HOA患者的镇痛效果	210人，105名治疗，105安慰剂组	200至400 mg, 口服，每天1次	12月	无缓解疼痛	ISRCTN91859104^[57]

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