Prophylactic therapy with subcutaneous C1 inhibitor reduces hereditary angioedema attacks
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Long-term subcutaneous treatment with a C1 inhibitor decreased the frequency and severity of hereditary angioedema attacks as well as the use of on-demand medications, according to a study published in Allergy and Asthma Proceedings.
C1 inhibitors have an over 30-year track record of safety for treating patients with hereditary angioedema (HAE), including children and adults, and pregnant and lactating women, Timothy Craig, DO, clinical researcher with the department of medicine, pediatrics and biomedical sciences at Pennsylvania State University, told Healio.
“The concern is that prior to this study, C1 inhibitors required intravenous therapy, which has a significant drug burden. This study demonstrated the safety and efficacy of subcutaneous C1 inhibitor administration,” Craig said.
“The dose allowed most people to obtain normal or near-normal levels of C1 inhibitor protein with an efficacy of approximately 85% mean reduction of attacks,” he continued.
Craig and colleagues evaluated data from patients aged 6 years and older enrolled in an open-label extension of the phase 3 COMPACT trial, a multicenter, randomized, parallel-arm study that evaluated the use of C1 esterase inhibitor subcutaneous (human) (Haegarda, CSL Behring), a nanofiltered C1 inhibitor, for the prevention of HAE attacks.
Patients received single injections in 40 IU/kg (n = 63) or 60 IU/kg (n = 63) doses of the subcutaneous C1 inhibitor twice per week for up to 52 weeks, or for up to 140 weeks for patients in the U.S.
This analysis includes data from the 63 patients (median age, 41 years; 57% women) assigned the 60 IU/kg dose — which has received FDA approval — including 24 who received treatment for at least 12 months. Prior to the study, this group had experienced a median of nine HAE attacks over a 3-month period. However, these participants were free of attacks attack for 98% of their days during 2.7 years of observation.
This group experienced a median of 0.09 (range, 0-4) HAE attacks per month and 1 (range, 0-48) attack per year, with 92% (n = 55) experiencing a greater than 50% reduction in attacks compared with baseline. Additionally, 49.2% (n = 31) experienced fewer than one attack a year.
Of the 24 U.S. patients treated for at least 12 months, 92% (n =22) experienced a 50% or greater reduction in the number of attacks compared with baseline, and 50% (n = 12) were attack free during the duration of the open-label extension study. This group experienced a median 0.017 (range, 0-2.4) attacks per month and 0.199 (range, 0-28.9) attacks per year.
Overall, 80.8% of U.S. participants treated with the 60 IU/kg dose did not have any attacks for 6 months or more and 70.8% of them were attack-free for 12 months or more. The researchers reported 371 HAE attacks during the open-label extension study, 61.7% of which were treated with on-demand medications, and 83.8% of these resolving with a single dose of rescue medication. Further, the researchers characterized 49% of these attacks requiring treatment as severe, 39% as moderate and 12% as mild.
Also, 39 patients (61.9%) receiving 60 IU/kg doses did not use on-demand treatment at all for their HAE attacks.
Among 1,811 adverse events resulting from 18,699 injections in the overall patient population, 99% were not serious, 87% were mild and 97% resolved. The most common adverse events were injection-site reactions, occurring 0.06 times per injection in the group receiving 60 IU/kg.
“The safety and efficacy were what we expected by pharmacokinetics,” Craig said. “We were happy that most people obtained a plateau of C1 inhibitor protein way above the 40% level that reduces the expected attack rate.”
Also, the researchers said these results have reframed what patients expect from their therapy as attack frequency decreases to one or fewer per year, with potential decreases in fear, more normal lifestyles and a shift in strategy from on-demand treatment to long-term prophylaxis.
“Using an subcutaneous C1 inhibitor protein enables patients to obtain normal or near-normal levels of C1 inhibitor, which is the protein that is deficient in hereditary angioedema,” Craig said.
The researchers called for more research in the impact that comorbid disease may have on disease as well as the use of this therapy in a wider variety of patient groups including pediatric, nonwhite and elderly populations.
“The next step is getting approval for all ages, including very young children,” Craig said.
For more information:
Timothy Craig, DO, can be reached at tcraig@pennstatehealth.psu.edu.