Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy.
Dermatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy.
Autoimmun Rev. 2021 Apr;20(4):102784. doi: 10.1016/j.autrev.2021.102784. Epub 2021 Feb 17.
Polyarteritis nodosa (PAN) is a medium vessels vasculitis variously involving different organs and systems, sometimes with an aggressive course, leading to death or disability in a significant number of cases. First-line treatment usually relies on steroids and classical immunosuppressants, but a growing number of case reports and small case series shows the potential role of biologic drugs, mostly anti-tumor necrosis factor (TNF)-α agents, in inducing and maintaining remission in patients affected by PAN. Similarly, the recently described autoinflammatory disease named deficit of adenosine deaminase 2 (DADA2), considered by several experts as a more precocious and aggressive variant of PAN, seems to respond to a prompt treatment with TNF-α inhibitors. The aim of this review is to collect all existing evidences about the use of biologic drugs in PAN and DADA2. Fifty-one articles published during the last 15 years were retrieved, including 58 and 76 patients affected by PAN and DADA2, respectively, and treated with biologic drugs. The majority of subjects was treated with TNF-α inhibitors, whose effectiveness was reported in the treatment of such difficult-to-manage diseases, particularly in DADA2. Among the other biologic drugs, Tocilizumab was successfully employed in some subjects affected by PAN who did not respond to TNF-α inhibitors, while Rituximab did not give substantial benefits neither in PAN nor in DADA2. Only few data exist about the role of Janus-kinase inhibitors and anti-IL1 agents. This study provides the first comprehensive assessment of biologic agents in both PAN and DADA2, with encouraging results especially in the context of TNF-α inhibitors. Nevertheless, due to the lack of prospective, randomized, case control studies, further efforts should be made in order to fully elucidate the role of these drugs in such rare and life-threatening conditions.
结节性多动脉炎（PAN）是一种中等大小血管炎，可累及不同的器官和系统，有时具有侵袭性病程，导致大量病例死亡或残疾。一线治疗通常依赖于类固醇和经典免疫抑制剂，但越来越多的病例报告和小病例系列表明，生物药物，主要是抗肿瘤坏死因子（TNF）-α 制剂，在诱导和维持 PAN 患者缓解方面具有潜在作用。同样，最近描述的自身炎症性疾病命名为腺苷脱氨酶 2 缺乏症（DADA2），被多位专家认为是 PAN 的一种更早和更具侵袭性的变异型，似乎对 TNF-α 抑制剂的治疗反应迅速。本综述的目的是收集所有关于生物药物在 PAN 和 DADA2 中应用的现有证据。检索到过去 15 年发表的 51 篇文章，包括分别患有 PAN 和 DADA2 的 58 例和 76 例患者，并用生物药物治疗。大多数患者接受 TNF-α 抑制剂治疗，其有效性在治疗这些难以控制的疾病方面得到了报道，特别是在 DADA2 中。在其他生物药物中，Tocilizumab 成功地用于一些对 TNF-α 抑制剂无反应的 PAN 患者，而利妥昔单抗在 PAN 和 DADA2 中均未带来实质性益处。关于 Janus 激酶抑制剂和抗 IL1 制剂的作用仅有少量数据。本研究首次全面评估了生物制剂在 PAN 和 DADA2 中的作用，结果令人鼓舞，尤其是在 TNF-α 抑制剂的背景下。然而，由于缺乏前瞻性、随机、病例对照研究，仍需进一步努力，以充分阐明这些药物在这些罕见且危及生命的情况下的作用。
