Subcutaneous pdC1-INH in Patients with Hereditary Angioedema in Real-World Practice

Hereditary Angioedema Due to C1 Inhibitor Deficiency

C1-INH-HAE is characterized by recurrent attacks of swelling, which can be life-threatening in the case of laryngeal involvement. Treatment includes on-demand therapy for rapid swelling relief, short-term prophylaxis to prevent attacks when exposed to known triggers, and long-term prophylaxis to reduce the frequency and severity of attacks. Treatment is individualized, and while every patient needs on-demand therapy, long-term prophylaxis (LTP) may not be necessary for all.

Human Plasma-Derived C1-INH Concentrate

Among the preparations for LTP, intravenously (i.v.) administered pdC1-INH has demonstrated a 50% reduction in attack frequency compared to placebo. However, even with this treatment, patients experienced an average of 6.26 attacks over 12 weeks, which were treated with rescue infusions of pdC1-INH.

Subcutaneously (s.c.) administered pdC1-INH was evaluated in the COMPACT study, where it also demonstrated effectiveness in reducing the frequency of attacks. Unlike i.v. pdC1-INH, s.c. administration led to the maintenance of plasma C1-INH activity above 40% of normal levels, which is the threshold for clinically significant effect. In the EU, s.c. pdC1-INH is approved for LTP at a dose of 60 IU/kg body weight 2× weekly.

Results of s.c. pdC1-INH Treatment in the Study Cohort

The authors of this case series collected data from medical records of 5 patients with inadequately controlled C1-INH-HAE on previous LTP or with problematic venous access, who were referred to the Milan center and treated with s.c. pdC1-INH. The group included 4 women and 1 man aged 23–60 years:

• In a 23-year-old female patient weighing 60 kg, who previously did not use LTP, prophylaxis with s.c. pdC1-INH at a dose of 1500 IU 2× weekly (50 IU/kg/week) reduced the monthly frequency of attacks from 3 to 2.11.
• In a 45-year-old woman (70 kg) previously on LTP with intravenous human C1-esterase inhibitor at a dose of 1000 IU 2× weekly, the occurrence of attacks was reduced during s.c. pdC1-INH administration at a dose of 1500 IU 3× weekly (64.29 IU/kg/week) from 3.46 to 0.12 per month.
• In a 60-year-old man (70 kg) unsuccessfully treated with s.c. pdC1-INH at 1500 IU 2× weekly, increasing the dosing frequency to 3× weekly led to a reduction in attack frequency from 5.26 to 1.12 per month.
• In a 45-year-old woman (69 kg) without previous LTP, s.c. pdC1-INH administered at 1500 IU 3× weekly (65.22 IU/kg/week) was associated with a reduction in attack frequency from 8.8 to 4.3 per month.
• Finally, in a 49-year-old woman (70 kg) previously treated with oral tranexamic acid at a dose of 1 g/3 days, switching to s.c. pdC1-INH at a dose of 1500 IU 2× weekly (42.86 IU/kg/week) led to a reduction in attack frequency from 2.46 to 0.44 per month

Even though the described patients used s.c. pdC1-INH at lower doses (42.86–65.22 IU/kg/week), all experienced a 30–97% reduction in attack frequency compared to the previous period when they used another LTP or did not use any LTP. In 1 patient, increasing the dosing frequency of s.c. pdC1-INH from 2× to 3× weekly led to an improvement. The duration of observation ranged from 2.6 to 48 months.

In 2 patients, adverse events were recorded, which were limited to the injection site and were of mild severity.

Conclusion

Subcutaneous pdC1-INH represents a therapeutic alternative in patients with hereditary angioedema. Depending on the physician's decision, it is a suitable approach for selected HAE patients with C1 inhibitor deficiency inadequately controlled by other long-term prophylactic agents.

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Source: Zanichelli A., Suffritti C., Popescu Janu V. et al. Real-life experience with subcutaneous plasma-derived C1-inhibitor for long-term prophylaxis in patients with hereditary angioedema: a case series. Front Allergy 2022 Apr 11; 3: 818741, doi: 10.3389/falgy.2022.818741.