Yiu Zenas Z N, Warren Richard B
a Dermatology Centre, Salford Royal NHS Foundation Trust , The University of Manchester, Manchester Academic Health Science Centre , Manchester , UK.
Expert Opin Investig Drugs. 2017 Feb;26(2):243-249. doi: 10.1080/13543784.2017.1274734. Epub 2017 Jan 1.
The approved biologic therapies are effective for the treatment of psoriasis, but have limitations. Tildrakizumab has a different mechanism of action and is a humanized immunoglobulin G1κ that binds to the p19 subunit of IL23. Areas covered: Phase I, II and III clinical trials investigated the pharmacokinetics, efficacy, safety and immunogenicity of tildrakizumab for patients with psoriasis. The mean half-life of tildrakizumab is between 20.2 to 28.2 days. Tildrakizumab achieved a PASI 75 of 66% and 74% at week 16 for the doses of 100 mg and 200 mg respectively in a phase IIb randomised clinical trial (RCT), and PASI 75 of 61%/64% and 62%/66% at week 12 for 100 mg and 200 mg respectively in two phase III RCTs. Frequently associated adverse events include headache and upper respiratory tract infection. Expert opinion: By recent standards tildrakizumab has relatively modest efficacy, possibly due to a less intensive dosing regimen. Head-to-head RCTs in comparison with current therapies such as ustekinumab and secukinumab respectively are needed to understand its relative efficacy. In addition, trials in patients who have failed multiple biologics and patients with psoriatic arthritis would be helpful. The low frequency of injections in the tildrakizumab maintenance regimen may encourage adherence and aid persistence.
已获批的生物疗法对银屑病治疗有效，但存在局限性。替拉珠单抗具有不同的作用机制，是一种与人白细胞介素23（IL23）的p19亚基结合的人源化免疫球蛋白G1κ。涵盖领域：Ⅰ期、Ⅱ期和Ⅲ期临床试验研究了替拉珠单抗治疗银屑病患者的药代动力学、疗效、安全性和免疫原性。替拉珠单抗的平均半衰期在20.2至28.2天之间。在一项Ⅱb期随机临床试验（RCT）中，替拉珠单抗100mg和200mg剂量在第16周时分别达到66%和74%的银屑病面积和严重程度指数改善75%（PASI 75）；在两项Ⅲ期RCT中，100mg和200mg剂量在第12周时分别达到61%/64%和62%/66%的PASI 75。常见的不良事件包括头痛和上呼吸道感染。专家观点：按照近期标准，替拉珠单抗的疗效相对一般，可能是由于给药方案强度较低。需要分别与优特克单抗和司库奇尤单抗等现有疗法进行头对头RCT，以了解其相对疗效。此外，在多种生物制剂治疗失败的患者和银屑病关节炎患者中开展试验将有所帮助。替拉珠单抗维持治疗方案的注射频率较低，可能会提高依从性并有助于持续治疗。
