Bygum Anette, Caballero Teresa, Grumach Anete S, Longhurst Hilary J, Bouillet Laurence, Aberer Werner, Zanichelli Andrea, Botha Jaco, Andresen Irmgard, Maurer Marcus
1Department of Dermatology and Allergy Centre, Odense University Hospital, J.B. Winsløws Vej 4, Indgang 142, 5000 Odense C, Denmark.
2Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Clin Transl Allergy. 2019 Jul 19;9:37. doi: 10.1186/s13601-019-0272-9. eCollection 2019.
Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5-11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.
The Icatibant Outcome Survey (IOS) is an observational study evaluating the safety, tolerability, and efficacy of icatibant. We conducted descriptive analyses in younger (age < 65 years) versus elderly patients (age ≥ 65 years). Here, we report patient characteristics and safety-related findings.
As of February 2018, 872 patients with C1-INH-HAE type I/II were enrolled, of whom 100 (11.5%) were ≥ 65 years old. Significant differences between elderly versus younger patients, respectively, were noted for median age at symptom onset (17.0 vs 12.0 years), age at diagnosis (41.0 vs 19.4 years), and delay between symptom onset and diagnosis (23.9 vs 4.8 years) (P ≤ 0.0001 for all). Median age at diagnosis was significantly higher in elderly patients regardless of family history (P < 0.0001). Throughout the study, icatibant was used to treat 6798 attacks in 574 patients, with 63 elderly patients reporting 715 (10.5%) of the icatibant-treated attacks. No serious adverse events (SAEs) in elderly patients were judged to be possibly related to icatibant, whereas two younger patients reported three possibly related SAEs. Excluding off-label use and pregnancy (evaluated for regulatory purposes), the percentage of patients with at least one possibly/probably related AE was similar for elderly (2.0%) versus younger patients (2.7%). No deaths linked to icatibant treatment were identified. All related events in elderly patients were attributed to general disorders/administration site conditions, whereas related events in younger patients occurred across various system organ class designations.
Elderly patients with C1-INH-HAE were significantly older at diagnosis and had greater delay in diagnosis than younger patients. Elderly patients contributed to approximately 10% of the icatibant-treated attacks. Our analysis found similar AE rates (overall and possibly/probably related) in icatibant-treated elderly versus younger patients, despite the fact that elderly patients had significantly more comorbidities and were receiving a greater number of concomitant medications. Our analysis did not identify any new or unexpected safety concerns.
伴有C1抑制剂缺乏的遗传性血管性水肿（C1-INH-HAE）的特征是皮下或粘膜下组织反复肿胀。症状通常在5至11岁开始，并在青春期加重，但发作可发生在任何年龄且终生复发。老年患者的疾病病程鲜有报道。
艾替班特结果调查（IOS）是一项评估艾替班特安全性、耐受性和疗效的观察性研究。我们对年轻患者（年龄<65岁）和老年患者（年龄≥65岁）进行了描述性分析。在此，我们报告患者特征和与安全性相关的发现。
截至2018年2月，872例I/II型C1-INH-HAE患者入组，其中100例（11.5%）年龄≥65岁。老年患者与年轻患者在症状发作的中位年龄（17.0岁对12.0岁）、诊断年龄（41.0岁对19.4岁）以及症状发作至诊断的延迟时间（23.9年对4.8年）方面分别存在显著差异（所有P≤0.0001）。无论有无家族史，老年患者的诊断中位年龄均显著更高（P<0.0001）。在整个研究过程中，艾替班特用于治疗574例患者的6798次发作，63例老年患者报告了715次（10.5%）接受艾替班特治疗的发作。老年患者中未判定有任何严重不良事件（SAE）可能与艾替班特相关，而两名年轻患者报告了三次可能相关的SAE。排除超说明书用药和妊娠（出于监管目的进行评估），老年患者（2.0%）与年轻患者（2.7%）中至少有一次可能/很可能相关不良事件的患者百分比相似。未发现与艾替班特治疗相关的死亡病例。老年患者的所有相关事件均归因于全身疾病/给药部位情况，而年轻患者的相关事件发生在各种系统器官类别中。
C1-INH-HAE老年患者诊断时年龄显著更大，诊断延迟时间比年轻患者更长。老年患者约占接受艾替班特治疗发作的10%。我们的分析发现，在接受艾替班特治疗的老年患者与年轻患者中，不良事件发生率（总体以及可能/很可能相关的）相似，尽管老年患者合并症显著更多且正在接受更多的合并用药。我们的分析未发现任何新的或意外的安全问题。
