Three studies presented Saturday at the American Academy of Allergy, Asthma and Immunology 2019 Annual Meeting, held February 22-25 in San Francisco, California, discussed different topics related to hereditary angioedema and treatment with subcutaneous injection of C1-esterase inhibitor (C1-INH).
Three studies presented Saturday at the American Academy of Allergy, Asthma and Immunology 2019 Annual Meeting, held February 22-25 in San Francisco, California, discussed different topics, including quality of life, related to hereditary angioedema (HAE) and treatment with subcutaneous injection of C1-esterase inhibitor (C1-INH).
According to the FDA, HAE is caused by having insufficient amounts of plasma protein C1-INH and affects approximately 6000 to 10,000 people in the United States. People with HAE can develop rapid swelling of the hands, feet, limbs, face, intestinal tract, or airway. These attacks of swelling can occur spontaneously, or can be triggered by stress, surgery or infection.
As such, HAE is known to have a significant negative impact on patients’ health-related quality of life (HRQoL). One abstract evaluated the impact of long-term prophylaxis of C1-INH on HRQoL in patients with HAE treated in an open-label extension (OLE) of the pivotal phase 3 COMPACT trial. 1
In the OLE, patients with at least 4 HAE attacks within a consecutive 2-month period (N = 126) self-administered C1-INH (SC) 40 or 60 IU/kg twice weekly for up to 52 or 140 weeks. HRQoL was self-assessed by patients at various points during the OLE using several instruments, including the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, Hospital Anxiety and Depression Scale (H—DS), and Work Productivity and Activity Impairment (WPAI) assessment.
At 60 IU/kg, significant improvements from baseline to the end-of-study visit were observed on the EQ-5D, HADS, and 3 of 4 WPAI domains. Clinically meaningful improvements versus baseline (mean [95% confidence interval]) were observed on the Health State Value (0.07[0.01, 0.12]) and Visual Analogue Scale (7.45 [3.29, 11.62]) of the EQ-5D. Improvements were also noted on the HADS Depression (—0.95 [–1.57, –0.34]) and Anxiety (–1.23 [–2.08, –0.38]) scales and WPAI domains of Presenteeism (–23.33 [–34.86, –11.81]), Work Productivity Loss (–26.68 [–39.92, –13.44]), and Activity Impairment (–16.14 [–26.36, –5.91]).
Long-term prophylaxis with C1-INH leads to significant and clinically meaningful improvements in various HRQoL measures in patients with HAE, the researchers said.
In another abstract, researchers evaluated the long-term safety of C1-INH in an open-label extension of the phase 3 COMPACT trial.2 Patients at least 6 years of age with at least 4 attacks within 2 consecutive months pre-enrollment self-administered C1-INH 40 or 60 IU/kg twice weekly for 52 weeks (dose increases to 80 IU/kg were allowed for treatment optimization) or up to 140 weeks.
Safety endpoints included treatment-related serious adverse events (SAEs), AEs leading to premature discontinuation, AEs of special interest (thromboembolism, anaphylaxis), solicited AEs (injection-site reactions [ISRs]), hospitalizations for HAE, and clinically significant laboratory abnormalities.
Of 126 patients randomized, 110 completed the study. The AE rate (1811 events/18,699 injections) was not dose-related (40 vs 60 IU/kg: 11.3 vs 8.5 AEs/patient-year of exposure).
None of the 12 SAEs were assessed as treatment-related. One unrelated serious HAE attack resulted in hospitalization but did not lead to discontinuation There were no cases of related thromboembolic events or anaphylaxis.
ISRs accounted for 99% of treatment-related AEs (1251/1257 events) and were reported more frequently with the 40 IU/kg dose; 99% were mild and 92% occurred within 24 hours of injection. No patients had neutralizing anti-C1-INH antibodies at baseline or post-baseline visits.
The researchers said C1-INH has a favorable long-term safety profile in the prophylactic treatment of HAE, with no dose-dependent safety concerns,
In the third abstract, researchers presented patient-reported outcomes using a convenience sample outside of a clinical trial.3 A convenience sample of 41 US patients, 33 with self-reported type I/II HAE, completed a web-based survey. Patients were at least 18 years of age (mean =48) with 82% females. All have been receiving C1-INH(SC) for at least 3 months, 73% >5 months.
Most (70%) received both prophylactic and on-demand therapy prior to C1-INH; of those, 74% received Cinryze, 17% Berinert, 9% Danazol as prior prophylaxis.
Patients reported a median 3 attacks (of these 2 attacks required rescue medications) in a typical month prior to C1-INH, compared to a median 0 attacks and rescue medications used in the last month while receiving C1-INH.
Around half (52%) experienced no attacks in the last month while receiving C1-INH. About a quarter experienced a severe attack in a typical month prior to C1-INH compared to 9% during the last month on C1-INH. Compared with prior treatment, 68% felt “very much better” and 26% “a fair amount better” since receiving C1-INH.
Almost all were “very satisfied or fairly satisfied” with the treatment’s ability to fit treatment into schedule, ease to prepare, time to prepare, effectiveness in reducing the number of HAE attacks, and overall as a prophylactic medication.
1. Lumry WR, Craig TJ, Magerl MAK, et al. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks. Presented at: American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting; February 22-25, 2019; San Francisco, CA. Abstract 113.
2. Li HH, Craig TJ, Longhurst H, Cicardi M. Long-term safety o f subcutaneous c1-inhibitor in the prophylactic treatment of hereditary angioedema
Presented at: American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting; February 22-25, 2019; San Francisco, CA. Abstract 117.
3. Tachdjian R, Taqi M, Riley D, Krishnarajah, G. Impact of C1-INH(SC) on Type I/II hereditaryangioedema: Findings from a US patient survey. Presented at: American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting; February 22-25, 2019; San Francisco, CA. Abstract 140.