用于银屑病关节炎的司库奇尤单抗：安全性、疗效及患者选择
Ixekizumab for Psoriatic Arthritis: Safety, Efficacy, and Patient Selection.
作者信息
Miller John, Puravath Abin P, Orbai Ana-Maria
机构信息
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lyme Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
J Inflamm Res. 2021 Dec 17;14:6975-6991. doi: 10.2147/JIR.S229752. eCollection 2021.
OBJECTIVE
Ixekizumab is a monoclonal antibody targeting IL-17A and licensed for psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis. Review objectives were to summarize: 1) ixekizumab safety in people with PsA, 2) ixekizumab efficacy from Phase III randomized controlled trials, and 3) ixekizumab study participant PsA phenotypes.
METHODS
We conducted a search in PubMed limited to phase III randomized controlled trials (RCT) and corresponding long-term extension studies where the intervention was treatment with ixekizumab in a population with PsA.
RESULTS
We identified 17 publications and 13 met inclusion criteria. Injection site reactions (ISR) and allergic reactions occurred in up to 25.3% and 6.2% with ixekizumab and 4.5% and 1.85, respectively, with placebo. ISR occurred in 9.5-10.6% at 24 and 52 weeks with ixekizumab versus 3.2-3.5% with adalimumab (p < 0.01) in biologic-naïve PsA. Serious adverse events at 24 weeks occurred in 8.5% with adalimumab versus 3.5% with ixekizumab (p = 0.02), and at 52 weeks in 12.45 with adalimumab and 4.25 with ixekizumab (p < 0.01). Ixekizumab had similar efficacy to adalimumab across all PsA musculoskeletal, symptom and patient-reported outcome domains and surpassed adalimumab in psoriasis outcomes as well as all combined musculoskeletal and psoriasis outcomes. The study subject population was overwhelmingly white, balanced men-women, BMI at the obese threshold, had on average 7-year PsA duration and 15-year psoriasis duration. Disease activity was high with 7/66 swollen joints, 13/68 tender joints, 55% enthesitis, variable dactylitis (12-51%), and active psoriasis in >92%.
CONCLUSION
Ixekizumab treatment in PsA was associated with a statistically significant higher risk of injection site reactions versus placebo or adalimumab. Ixekizumab had statistically significantly fewer serious adverse events than adalimumab. Ixekizumab demonstrated efficacy for all PsA disease activity domains as well as for slowing radiographic disease progression. The main shortcoming of the ixekizumab PsA program is lack of representation of African American study participants.
目的
ixekizumab是一种靶向白细胞介素-17A的单克隆抗体，已获许可用于治疗银屑病、银屑病关节炎（PsA）和中轴型脊柱关节炎。综述目的是总结：1）ixekizumab在PsA患者中的安全性；2）来自III期随机对照试验的ixekizumab疗效；3）ixekizumab研究参与者的PsA表型。
方法
我们在PubMed中进行了检索，限于III期随机对照试验（RCT）以及相应的长期扩展研究，其中干预措施为在PsA患者群体中使用ixekizumab进行治疗。
结果
我们识别出17篇出版物，13篇符合纳入标准。使用ixekizumab时，注射部位反应（ISR）和过敏反应的发生率分别高达25.3%和6.2%，而使用安慰剂时分别为4.5%和1.85%。在初治PsA患者中，使用ixekizumab在24周和52周时ISR的发生率为9.5 - 10.6%，而使用阿达木单抗时为3.2 - 3.5%（p < 0.01）。24周时，使用阿达木单抗的严重不良事件发生率为8.5%，而使用ixekizumab时为3.5%（p = 0.02）；52周时，使用阿达木单抗的发生率为12.45%，使用ixekizumab时为4.25%（p < 0.01）。在所有PsA肌肉骨骼、症状及患者报告的结局领域，ixekizumab与阿达木单抗疗效相似，且在银屑病结局以及所有合并的肌肉骨骼和银屑病结局方面超过阿达木单抗。研究对象群体绝大多数为白人，男女比例均衡，BMI处于肥胖阈值，PsA平均病程7年，银屑病平均病程15年。疾病活动度较高，有7/66个关节肿胀、13/68个关节压痛、55%有附着点炎、不同程度的指（趾）炎（12 - 51%），超过92%有活动性银屑病。
结论
在PsA中，与安慰剂或阿达木单抗相比，ixekizumab治疗的注射部位反应风险在统计学上显著更高。与阿达木单抗相比，ixekizumab的严重不良事件在统计学上显著更少。Ixekizumab对所有PsA疾病活动领域均显示出疗效，以及在减缓影像学疾病进展方面也有疗效。Ixekizumab治疗PsA项目的主要缺点是缺乏非裔美国研究参与者的代表性。
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