Ghezzi Gioele, Ibba Luciano, Gargiulo Luigi, Narcisi Alessandra, Costanzo Antonio, Valenti Mario
Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele.
Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano.
Dermatol Reports. 2024 Nov 12. doi: 10.4081/dr.2024.10080.
Psoriasis is a chronic immune-mediated disease primarily affecting the skin. The most common subtype is plaque psoriasis, which can affect any body area, with a predilection for the knees, elbows, scalp, lumbosacral region, and genitalia. The European guidelines adopted in Italy recommend systemic therapies for moderate-to-severe psoriasis, defined by a Psoriasis Area and Severity Index (PASI) ≥ 10, Dermatology Life Quality Index (DLQI) ≥ 10, and/or Body Surface Area (BSA) ≥ 10. Over the past two decades, the development of biological agents has revolutionized psoriasis management, targeting specific cytokines such as TNF-α, IL-23, and IL-17. Among these, ixekizumab, secukinumab, brodalumab, and bimekizumab are approved for the treatment of moderate-to-severe plaque psoriasis. However, some patients require switching therapy because of primary/secondary ineffectiveness or side effects. We retrospectively analyzed 20 patients who had switched from one anti-IL-17 drug to another, assessing both safety and effectiveness. 70% of patients was represented by males, with a median age of 49.5 years. The most frequent comorbidities were arterial hypertension and hypercholesterolemia. Effectiveness was evaluated in terms of a 90% (PASI90) and 100% (PASI100) reduction in PASI compared to baseline at 16 and 52 weeks. Before switching to the current IL-17 inhibitor, seven patients had failed at least two biologics. Thirteen patients experienced a loss of effectiveness after more than 6 months (secondary ineffectiveness), whereas the other seven never showed improvement with the previous drug (primary ineffectiveness). Fourteen patients completed at least one year of follow-up. Two patients were lost during the follow-up, while four more are currently still under treatment without having completed the established temporal cut-off. Two patients switched to bimekizumab, nine to brodalumab, and nine to ixekizumab. At baseline, the median PASI was 10 (IQR 4.5). After 16 weeks, the median PASI decreased to 2 (IQR 5.5), and after one year, it was 1 (IQR 2). Eight patients (40%) and six patients (30%) achieved PASI 90 and PASI 100 at 16 weeks, respectively. After one year, sustained effectiveness was observed with PASI 90 (57.1%), PASI 100 (35.7%), and PASI ≤ 2 (78.6%). No serious adverse events or discontinuations due to adverse events were observed during the study period. Our study confirms the safety and effectiveness of intraclass switching among IL-17 antagonists, highlighting that an inter-class switch can be a valid option when patients fail to respond or lose effectiveness with an IL-17 inhibitor. However, further larger and longer studies are needed for a deeper understanding.
银屑病是一种主要影响皮肤的慢性免疫介导性疾病。最常见的亚型是斑块状银屑病,可累及身体任何部位,好发于膝盖、肘部、头皮、腰骶部和生殖器部位。意大利采用的欧洲指南推荐对中度至重度银屑病进行系统治疗,中度至重度银屑病的定义为银屑病面积和严重程度指数(PASI)≥10、皮肤病生活质量指数(DLQI)≥10和/或体表面积(BSA)≥10。在过去二十年中,生物制剂的发展彻底改变了银屑病的治疗方式,这些生物制剂靶向特定的细胞因子,如肿瘤坏死因子-α(TNF-α)、白细胞介素-23(IL-23)和白细胞介素-17(IL-17)。其中,依奇珠单抗、司库奇尤单抗、布罗达单抗和比美吉珠单抗被批准用于治疗中度至重度斑块状银屑病。然而,一些患者由于原发/继发无效或出现副作用而需要更换治疗方案。我们回顾性分析了20例从一种抗IL-17药物转换为另一种抗IL-17药物的患者,评估了安全性和有效性。70%的患者为男性,中位年龄为49.5岁。最常见的合并症是动脉高血压和高胆固醇血症。有效性根据与基线相比在第16周和第52周时PASI降低90%(PASI90)和100%(PASI100)进行评估。在转换为当前的IL-17抑制剂之前,7例患者至少有两种生物制剂治疗失败。13例患者在6个月以上出现疗效丧失(继发无效),而另外7例患者使用先前药物从未显示出改善(原发无效)。14例患者完成了至少一年的随访。2例患者在随访期间失访,另有4例患者目前仍在接受治疗,但未达到既定的随访时间节点。2例患者转换为比美吉珠单抗,9例转换为布罗达单抗,9例转换为依奇珠单抗。基线时,中位PASI为10(四分位间距4.5)。16周后,中位PASI降至2(四分位间距5.5),一年后为1(四分位间距2)。8例患者(40%)和6例患者(30%)在16周时分别达到PASI90和PASI100。一年后,观察到持续有效性,PASI90为57.1%,PASI100为35.7%,PASI≤2为78.6%。在研究期间未观察到严重不良事件或因不良事件而停药的情况。我们的研究证实了IL-17拮抗剂类内转换的安全性和有效性,强调当患者对IL-17抑制剂无反应或失去疗效时,跨类转换可能是一种有效的选择。然而,需要进一步开展更大规模、更长时间的研究以进行更深入的了解。