Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.
Tsinghua Clinical Research Institute (TCRI), School of Medicine, Tsinghua University, Beijing, China.
Clin Exp Dermatol. 2022 Sep;47(9):1627-1635. doi: 10.1111/ced.15237. Epub 2022 Jun 25.
Tumour necrosis factor inhibitors (TNFi) were the first biologics approved for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA). However, some patients are intolerant of or unresponsive to TNFi.
To investigate the therapeutic effect of interleukin (IL)-17 and IL-12/23 inhibitors in patients with PsO or psoriatic arthritis PsA who were intolerant of or had responded inadequately to TNFi therapy (TNFi-experienced patients).
A systematic review of randomized controlled trials searched from the PubMed, Cochrane Library and Embase databases was conducted on 17 May 2021. Responses of 75% and 90% improvement on Psoriasis Area and Severity Index (PASI75, PASI90), 20%, 50% and 70% improvement on the American College of Rheumatology response criteria (ACR20, ACR50, ACR70), and full resolution of dactylitis/enthesitis were used to assess the treatment efficacy.
In total, 7 studies with a total of 3398 patients with PsA were included, 1330 of whom were intolerant of or had responded inadequately to TNFi. All studies were categorized as having low risk of bias. For IL-17A inhibitors, there were significantly higher achievements in all of the endpoints compared with placebo, but the proportions of patients achieving these endpoints were lower in TNFi-experienced patients compared with TNFi-naïve patients. However, the differences between TNFi-experienced and TNFi-naïve patients were significant only for ACR responses and for full resolution of enthesitis. For IL-12/23 inhibitors, only the results for ACR20 response were reported. Significantly more TNFi-experienced patients achieved ACR20 response compared with patients receiving placebo, and the differences in treatment efficacy between TNFi-experienced and TFNi-naïve patients was not significant.
IL-17A and IL-12/23 inhibitors still had efficacy for patients with PsO or PsA had failed or were intolerant to TNFi therapy; however, the efficacy was lower than that in TNFi-naïve patients. Further studies to confirm these findings are warranted.
肿瘤坏死因子抑制剂（TNFi）是首批获批用于治疗银屑病（PsO）和银屑病关节炎（PsA）的生物制剂。然而，一些患者对 TNFi 不耐受或无应答。
研究白细胞介素（IL）-17 和 IL-12/23 抑制剂在对 TNFi 治疗不耐受或应答不足（TNFi 经验患者）的 PsO 或 PsA 患者中的治疗效果。
于 2021 年 5 月 17 日对 PubMed、Cochrane 图书馆和 Embase 数据库进行了系统评价的随机对照试验检索。75%和 90%的银屑病面积和严重程度指数（PASI75、PASI90）改善、20%、50%和 70%的美国风湿病学会反应标准（ACR20、ACR50、ACR70）改善以及掌跖关节炎/肌腱端炎的完全缓解被用于评估治疗效果。
共纳入了 7 项共 3398 例 PsA 患者的研究，其中 1330 例患者对 TNFi 不耐受或应答不足。所有研究均被归类为低偏倚风险。对于 IL-17A 抑制剂，与安慰剂相比，所有终点均有显著更高的达标率，但 TNFi 经验患者的达标率低于 TNFi 初治患者。然而，仅在 ACR 反应和肌腱端炎的完全缓解方面，TNFi 经验患者与 TNFi 初治患者之间的差异有统计学意义。对于 IL-12/23 抑制剂，仅报告了 ACR20 反应的结果。与接受安慰剂的患者相比，更多的 TNFi 经验患者达到 ACR20 反应，且 TNFi 经验患者与 TNFi 初治患者之间的疗效差异无统计学意义。
IL-17A 和 IL-12/23 抑制剂对 TNFi 治疗失败或不耐受的 PsO 或 PsA 患者仍有效，但疗效低于 TNFi 初治患者。需要进一步的研究来证实这些发现。
