Paradoxical Reactions: Anti-Tumor Necrosis Factor Alpha Agents, Ustekinumab, Secukinumab, Ixekizumab, and Others.
Paradoxical Reactions: Anti-Tumor Necrosis Factor Alpha Agents, Ustekinumab, Secukinumab, Ixekizumab, and Others.
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DOI：
10.1159/000479475
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发表时间：
2018-01-01
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影响因子：
--
通讯作者：
Puig, Lluis
中科院分区：
文献类型：
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作者：
Puig, Lluis
生物制剂治疗期间的副反应可定义为在治疗患者的另一种疾病时出现或加重通常对该类药物有反应的病理学疾病，该疾病通常保持在控制范围内（即使可能存在形态学或表型变化）。在接受抗肿瘤坏死因子（TNF）α药物治疗的患者中，最初将副反应描述为孤立病例报告或病例系列，首先在炎性风湿性疾病中，随后在银屑病和炎性肠病中。随后报告了其他生物药物或类别的副作用（例如，托珠单抗），即使在某些情况下，疗效不足或表型转换可能难以与真正的反常反应区分。本章将讨论最常报告的反常反应的变体：掌跖脓疱和银屑病样反应、银屑病关节炎、汗腺炎、炎症性肠病、葡萄膜炎、坏疽性脓疡、肉芽肿反应和血管炎。这些涉及多种免疫途径的复杂疾病的潜在病理机制很可能是细胞因子失衡，用替代抗p40或抗IL-17 A生物制剂替代抗TNF α药物可能非常有用。副作用可导致严重残疾，早期识别和治疗这些药物类效应至关重要，特别是当原发性疾病相对缺乏治疗替代品时，其再激活可能会产生灾难性后果。对接受新生物制品药物治疗的患者进行密切监测是发现和描述新的反常反应所必需的。
Paradoxical reactions during treatment with a biologic agent can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition, which usually remains under control (even though there may be a change in morphology or phenotype). Paradoxical reactions were initially described as isolated case reports or case series in patients treated with anti-tumor necrosis factor (TNF) alpha agents, first in inflammatory rheumatic diseases, later in psoriasis and inflammatory bowel disease. Paradoxical reactions have subsequently been reported with other biological drugs or classes (e.g., tocilizumab), even though in some cases insufficient efficacy or phenotype switch may be difficult to differentiate from true paradoxical reactions. This chapter will deal with the most frequently reported variants of paradoxical reactions: palmoplantar pustular and psoriasiform reactions, psoriatic arthritis, hidradenitis, inflammatory bowel disease, uveitis, pyoderma gangrenosum, granulomatous reactions, and vasculitis. The underlying pathomechanism in these complex diseases with involvement of multiple immunological pathways is most likely a cytokine imbalance, and substitution of the anti-TNFalpha agent by an alternative anti-p40 or anti-IL-17A biologic may be extremely helpful. Paradoxical reactions can cause serious handicap, and early recognition and treatment of these drug class effects is of paramount importance, especially when the primary disease is relatively devoid of therapeutic alternatives and its reactivation may have catastrophic consequences. Close surveillance of patients treated with newly available biologic drugs is necessary to detect and describe new paradoxical reactions.