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多系统失败型银屑病患者:意大利多中心队列研究患者特征及生物治疗应答。

Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

机构信息

Section of Dermatology and Venereology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", Bari, Italy.

Department of Medical Sciences, Dermatology Clinic, University of Turin, Turin, Italy.

出版信息

Int J Dermatol. 2024 Mar;63(3):351-358. doi: 10.1111/ijd.17005. Epub 2024 Jan 5.

Abstract

INTRODUCTION

Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response.

METHODS

Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors.

RESULTS

In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121).

CONCLUSIONS

The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians.

摘要

简介

已经将生物制剂治疗失败多次的银屑病患者定义为“多失败”,尽管对于此类人群的特征、合并症和最佳治疗策略尚无明确的数据。如今,鉴于下一代生物制剂和可用的生物制剂数量众多,当≥4 种生物制剂未能获得良好反应时,患者即被认为是“多失败”。

方法

比较多失败患者和接受 IL-23 或 IL-17 抑制剂治疗的一般银屑病患者的抗白细胞介素药物的疗效。

结果

共有 97 例多失败患者(≥4 线生物制剂)与一般队列中的 1057 例患者进行了比较。多失败组当前的药物有 risankizumab(34)、ixekizumab(23)、guselkumab(21)、brodalumab(7)、tildrakizumab(5)、ustekinumab(4)、secukinumab(2)和 certolizumab pegol(1)。在多失败组中,银屑病发病年龄(平均 29.7 岁 vs. 35.1 岁,P < 0.001)、并发银屑病关节炎(45.4% vs. 26.9%,P < 0.001)、糖尿病(30.9% vs. 10.9%,P < 0.001)和心血管合并症(54.6% vs. 39.8%,P = 0.005)存在显著差异。在多失败患者中,目前的生物治疗显示出良好的初始反应(第 16 周 PASI90 和 100 分别为 41.24%和 27.84%);40 周后,反应趋于下降。抗白细胞介素-17 药物在第 28 周(P < 0.001)和第 40 周(P = 0.007)达到 PASI90 方面显示出优于白细胞介素-23 药物的临床优势,此后达到平台期。相比之下,白细胞介素-23 药物的改善速度较慢,但呈渐进性,持续至 52 周。PASI100 也呈现出类似的趋势(第 28 周 P = 0.032;第 40 周 P = 0.121)。

结论

多失败患者的特点是合并症较多,炎症性疾病病史较长,且常早于全身生物治疗的引入。需要进一步研究以确定更具体的标准,以便临床医生作为指南应用。

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