Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey

Anette Bygum, Teresa Caballero, Anete S Grumach, Hilary J Longhurst, Laurence Bouillet, Werner Aberer, Andrea Zanichelli, Jaco Botha, Irmgard Andresen, Marcus Maurer, IOS Study Group, W Aberer, A S Grumach, R Hakl, A Bygum, C Blanchard Delaunay, I Boccon-Gibod, L Bouillet, B Coppere, A Du Thanh, C Dzviga, O Fain, B Goichot, A Gompel, S Guez, P Y Jeandel, G Kanny, D Launay, H Maillard, L Martin, A Masseau, Y Ollivier, A Sobel, E Aygören-Pürsün, M Baş, M Bauer, K Bork, J Greve, M Magerl, I Martinez-Saguer, M Maurer, U Strassen, E Papadopoulou-Alataki, F Psarros, Y Graif, S Kivity, A Reshef, E Toubi, F Arcoleo, M Bova, M Cicardi, P Manconi, G Marone, V Montinaro, M Triggiani, A Zanichelli, M L Baeza, T Caballero, R Cabañas, M Guilarte, D Hernandez, C Hernando de Larramendi, R Lleonart, T Lobera, L Marqués, B Saenz de San Pedro, J Björkander, C Bethune, T Garcez, H J Longhurst, Anette Bygum, Teresa Caballero, Anete S Grumach, Hilary J Longhurst, Laurence Bouillet, Werner Aberer, Andrea Zanichelli, Jaco Botha, Irmgard Andresen, Marcus Maurer, IOS Study Group, W Aberer, A S Grumach, R Hakl, A Bygum, C Blanchard Delaunay, I Boccon-Gibod, L Bouillet, B Coppere, A Du Thanh, C Dzviga, O Fain, B Goichot, A Gompel, S Guez, P Y Jeandel, G Kanny, D Launay, H Maillard, L Martin, A Masseau, Y Ollivier, A Sobel, E Aygören-Pürsün, M Baş, M Bauer, K Bork, J Greve, M Magerl, I Martinez-Saguer, M Maurer, U Strassen, E Papadopoulou-Alataki, F Psarros, Y Graif, S Kivity, A Reshef, E Toubi, F Arcoleo, M Bova, M Cicardi, P Manconi, G Marone, V Montinaro, M Triggiani, A Zanichelli, M L Baeza, T Caballero, R Cabañas, M Guilarte, D Hernandez, C Hernando de Larramendi, R Lleonart, T Lobera, L Marqués, B Saenz de San Pedro, J Björkander, C Bethune, T Garcez, H J Longhurst

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Elderly; Hereditary angioedema; Icatibant Outcome Survey; Safety.

Conflict of interest statement

Competing interestsAB has received research grant support and/or speaker/consulting fees from CSL Behring and Shire*, and participated in a clinical trial for BioCryst and Jerini AG. She is an advisor for the HAE Scandinavian Patient Organization. TC has received speaker fees from CSL Behring, Novartis, and Shire,* consulting fees from BioCryst, CSL Behring, Novartis, and Shire,* funding for travel/meeting attendance from CSL Behring, Novartis, and Shire,* and has participated in clinical trials/registries for BioCryst, CSL Behring, Novartis, Pharming, and Shire.* She is a researcher from the IdiPAZ program for promoting research activities. ASG has been a speaker/consultant for BioCryst, CSL Behring, and Shire.* HJL has received research grant support and/or speaker/consulting fees from Adverum, BioCryst, CSL Behring, Shire,* and Sobi. LB has received honoraria from BioCryst, CSL Behring, Novartis, Pharming, and Shire* and her institute has received research funding from CSL Behring, GlaxoSmithKline, Novartis, Roche, and Shire.* WA has acted as a medical advisor and speaker for BioCryst, CSL Behring, Pharming, and Shire* and has received funding to attend conferences/educational events, and donations to his departmental fund from and participated in clinical trials for Shire.* AZ has received speaker fees from CSL Behring, Shire,* and Sobi; consulting fees from CSL Behring and Shire* and has acted on the medical/advisory boards for CSL Behring and Shire.* JB and IA are full-time employees of Shire,* Zug, Switzerland. MM has received research grant support and/or speaker/consulting fees from BioCryst, CSL Behring, and Shire*. *A Takeda company.

Figures

Fig. 1
Fig. 1
a Age at diagnosis in elderly and younger patients, with and without a family history and b delay in diagnosis in elderly and younger patients, with and without a family historya. The horizontal line inside each box indicates the median, the lower and upper borders of each box indicate the first and third quartiles, and the lowest and highest horizontal lines outside the box indicate the minimum and maximum value. aA total of 113 patients with a family history had a negative delay in diagnosis (wherein diagnosis occurred before onset of symptoms, based on confirmatory laboratory testing); younger, n = 108; elderly, n = 5. Likewise, a total of five patients with no family history had a negative delay in diagnosis, all in the younger group

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