Sanan Neha, Schend Jason, Rowane Marija, Hostoffer Robert
Department of Pulmonary Critical Care, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio.
Allergy Rhinol (Providence). 2020 Jun 22;11:2152656720937694. doi: 10.1177/2152656720937694. eCollection 2020 Jan-Dec.
Interleukin-1 (IL-1) antagonists have been successful in the management of monogenic auto-inflammatory diseases, notably classic hereditary fever syndromes, such as Familial Mediterranean Fever (FMF). Anakinra (Kineret®), a human recombinant IL-1 receptor antagonist (IL-1Ra), has been clinically effective in the management of persistent auto-inflammation, such as FMF. Few studies report anaphylaxis in response to anakinra, which were resolved with an anakinra desensitization or the anti-IL-1β monoclonal antibody canakinumab (ILARIS®). We describe the first reported desensitization protocol to canakinumab.
A 51-year-old man with a prior history of FMF presented with history of failed colchicine, nonsteroidal anti-inflammatory drug, and anakinra trials. Anakinra desensitization and canakinumab intradermal testing (IDT) resulted in anaphylactic and allergic symptoms, respectively. Expedited desensitization to canakinumab was successfully performed with 15-minute intervals between 13 doses of incremental increase to 150 mg.
Biological agents are immune modulators that may evoke unanticipated hypersensitivity reactions, including anaphylaxis. These anaphylactic reactions to biologics have been infrequently reported, but the expanding market may increase the risk of IgE-mediated hypersensitivities and subsequent need for desensitization protocols. The current, expedited desensitization evaluated several published protocols involving anakinra desensitization to determine appropriate dosing for canakinumab.
We report the gastrointestinal intolerance and continued FMF flares on colchicine, followed by anaphylactic responses to anakinra and allergic reaction to IDT of canakinumab, in the present case of FMF. Our novel, expedited canakinumab desensitization protocol serves as an effective and alternative therapy in cases when other appropriate biologic agents are not tolerated.
白细胞介素-1（IL-1）拮抗剂已成功用于单基因自身炎症性疾病的治疗，尤其是经典遗传性发热综合征，如家族性地中海热（FMF）。阿那白滞素（Kineret®），一种人重组IL-1受体拮抗剂（IL-1Ra），在治疗持续性自身炎症，如FMF方面已显示出临床疗效。很少有研究报道使用阿那白滞素后发生过敏反应，这些过敏反应通过阿那白滞素脱敏或抗IL-1β单克隆抗体卡那单抗（ILARIS®）得以解决。我们描述了首例报道的卡那单抗脱敏方案。
一名51岁有FMF病史的男性患者，秋水仙碱、非甾体抗炎药及阿那白滞素治疗均失败。阿那白滞素脱敏及卡那单抗皮内试验（IDT）分别导致过敏反应和过敏症状。以15分钟的间隔，将卡那单抗剂量逐步增加至150mg，共13剂，成功完成了卡那单抗的快速脱敏。
生物制剂是免疫调节剂，可能引发意想不到的超敏反应，包括过敏反应。这些生物制剂引发的过敏反应鲜有报道，但不断扩大的市场可能会增加IgE介导的超敏反应风险以及后续对脱敏方案的需求。当前的快速脱敏方案评估了多项已发表的涉及阿那白滞素脱敏的方案，以确定卡那单抗的合适剂量。
在本FMF病例中，我们报告了患者出现胃肠道不耐受及秋水仙碱治疗下FMF仍持续发作，随后对阿那白滞素出现过敏反应，对卡那单抗IDT出现过敏反应。我们新颖的卡那单抗快速脱敏方案在其他合适的生物制剂无法耐受的情况下，可作为一种有效的替代治疗方法。
