Longhurst Hilary J, Cancian Mauro, Grivcheva-Panovska Vesna, Koleilat Majed, Magerl Markus, Savic Sinisa, Stobiecki Marcin, Tachdjian Raffi, Healy Bridget, Yea Christopher M, Audhya Paul K, Bouillet Laurence
Department of Immunology, Auckland City Hospital, Te Toka Tumai and University of Auckland, Auckland, New Zealand.
Department of Systems Medicine, University Hospital of Padua, Padua, Italy.
Clin Rev Allergy Immunol. 2024 Dec;67(1-3):83-95. doi: 10.1007/s12016-024-09006-1. Epub 2024 Nov 7.
Long-term prophylaxis (LTP) has been shown to reduce the frequency of hereditary angioedema (HAE) attacks; however, attacks occurring in patients receiving LTP have not been well characterized. The objective of this systematic review was to evaluate the proportion of type I/II HAE (HAE-C1INH) patients who experience attacks while receiving LTP, the characteristics of these attacks, and associated on-demand therapy use. A systematic search was conducted in PubMed to identify studies reporting LTP use with plasma-derived C1 inhibitor (pdC1INH), lanadelumab, berotralstat, androgens, or antifibrinolytics in patients with HAE-C1INH. Forty-five primary studies met the inclusion criteria. In phase 3 trials, attack-free rates were 40% for subcutaneous pdC1INH 60 IU/kg twice weekly at 16 weeks, and 44% for lanadelumab 300 mg every second week at 6 months (77% during steady-state [days 70-182]); there was no difference in attack-free rate for berotralstat 150 mg versus placebo at 24 weeks. Phase 3 studies reported a lower average attack severity with subcutaneous and intravenous pdC1INH versus placebo. With lanadelumab and berotralstat, the prophylactic treatment effect was more pronounced in peripheral attacks than in abdominal and laryngeal attacks. Laryngeal attacks accounted for 2%-7% of all attacks in observational and interventional studies, regardless of the LTP agent received. On-demand therapy was used in 49%-94% of attacks occurring in the presence of LTP. In conclusion, patients receiving LTP experienced attacks in all anatomic locations, including the larynx. Most attacks were treated with on-demand therapy, although outcomes were not reported. Access to on-demand therapy remains essential for all people with HAE-C1INH.
长期预防（LTP）已被证明可降低遗传性血管性水肿（HAE）发作的频率；然而，接受LTP治疗的患者发生的发作尚未得到充分描述。本系统评价的目的是评估接受LTP治疗的I/II型HAE（HAE-C1INH）患者发生发作的比例、这些发作的特征以及相关的按需治疗使用情况。在PubMed中进行了系统检索，以确定报告在HAE-C1INH患者中使用LTP联合血浆源性C1抑制剂（pdC1INH）、拉那度单抗、贝罗司他、雄激素或抗纤维蛋白溶解剂的研究。45项主要研究符合纳入标准。在3期试验中，皮下注射pdC1INH 60 IU/kg每周两次，16周时无发作率为40%，拉那度单抗300 mg每两周一次，6个月时无发作率为44%（稳态期[第70 - 182天]为77%）；24周时，150 mg贝罗司他与安慰剂相比，无发作率无差异。3期研究报告，与安慰剂相比，皮下和静脉注射pdC1INH的平均发作严重程度较低。使用拉那度单抗和贝罗司他时，预防性治疗对外周发作的效果比对腹部和喉部发作更明显。在观察性和干预性研究中，无论接受何种LTP药物，喉部发作占所有发作的2% - 7%。在LTP存在的情况下发生的发作中，49% - 94%使用了按需治疗。总之，接受LTP治疗的患者在包括喉部在内的所有解剖部位都发生了发作。大多数发作采用按需治疗，但未报告结果。对于所有HAE-C1INH患者来说，获得按需治疗仍然至关重要。
