Escalating Doses of C1 Esterase Inhibitor (CINRYZE) for Prophylaxis in Patients With Hereditary Angioedema

Bernstein, Jonathan A.; Manning, M. A.; Li, Henry; White, Martha V.; Baker, James; Lumry, William R.; Davis-Lorton, Mark; Jacobson, Kraig W.; Gower, Richard; Broom, Colin; Schranz, Jennifer

doi:10.1016/j.jaip.2013.09.008

Cited by 50 publications

(33 citation statements)

References 12 publications

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“…Since administered C1-INH doses are unable to return functional C1-INH to normal levels in all patients, it is likely that individualization of the dose or administration frequency will be needed to achieve optimal responses in some patients [23]. In support of this, another study found that escalating the C1-INH dose to 2,500 U every 3 or 4 days for those who are not responsive to 1,000 U is well tolerated [27]. In addition, C1-INH was shown in a previous study to have a positive impact on the quality of life of patients [28].…”

Section: Discussionmentioning

confidence: 99%

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Aygören‐Pürsün

Soteres

Moldovan

et al. 2017

Int Arch Allergy Immunol

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Background: Hereditary angioedema (HAE) is a rare genetic disease causing unpredictable and potentially life-threatening subcutaneous and submucosal edematous attacks. Cinryze® (Shire ViroPharma Inc., Lexington, MA, USA), a nanofiltered C1 inhibitor (C1-INH), is approved in Europe for the treatment, preprocedure prevention, and routine prophylaxis of HAE attacks, and for the routine prophylaxis of attacks in the USA. This phase 3 study assessed the safety and efficacy of 2 C1-INH doses in preventing attacks in children aged 6-11 years. Methods: A randomized single-blind crossover study was initiated in March 2014. Results for the first 6 patients completing the study are reported here. After a 12-week qualifying observation period, patients were randomly assigned to 1 of 2 C1-INH doses, 500 or 1,000 U, every 3-4 days for 12 weeks and crossed over to the alternative dose for a second 12-week period. The primary efficacy endpoint was the number of angioedema attacks per month. Results: Six females with HAE type I and a median age of 10.5 years received 2 doses of C1-INH (500 and 1,000 U). The mean (SD) difference in the number of monthly angioedema attacks between the baseline observation period and the treatment period was -1.89 (1.31) with 500 U and -1.89 (1.11) with 1,000 U. During the treatment periods, cumulative attack severity, cumulative daily severity, and the number of attacks needing acute treatment were lower. No serious adverse events or study drug discontinuations occurred. Conclusions: Interim findings from this study indicate that routine prevention with intravenous administration of C1-INH is efficacious, safe, and well tolerated in children ≥6 years of age.

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Section: Discussionmentioning

confidence: 99%

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Aygören‐Pürsün

Soteres

Moldovan

et al. 2017

Int Arch Allergy Immunol

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“…Although Berinert has not been approved for this indication, all recent treatment guidelines recommend plasma-derived C1-INH as an option for LTP, 4,12,13,18,19,33 and the efficacy of another marketed plasma-derived, nanofiltered C1-INH product (Cinryze) for LTP has been confirmed in two placebo-controlled trials, 15,34 with further support from several uncontrolled trials. 14,15,35 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of an Intravenous C1-Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary angioedema

Craig

Shapiro²,

Vegh

et al. 2017

Allergy�Rhinol (Providence)

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Background:The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis.Objective:This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP).Methods:The international registry (2010–2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason.Results:The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500–3000 IU), with a median time interval between infusion and a subsequent pnfC1-INH–treated attack of 72.0 hours (range, 0.0–166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INH–treated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port).Conclusion:In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration.

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“…Although the reduction in attack rate was only~50% in the pivotal study, an open-label follow-up study showed the reduction in attacks to be greater than 90% (Zuraw & Kalfus, 2012). Not all patients achieve good control of their angioedema on the recommended starting dose (1000 units twice/week), and it is sometimes necessary to vary the dose or frequency of pdC1INH (Bernstein et al, 2014). All patients using prophylactic pdC1INH are encouraged to learn self-infusion, which minimizes the disruption of daily life and has been shown to be safe (Tourangeau et al, 2012).…”

Section: Prophylactic Treatment For Hae-c1inhmentioning

confidence: 97%

How we manage persons with hereditary angioedema

Zuraw

Christiansen

2016

Br J Haematol

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Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality. Several novel therapies introduced since 2008 have dramatically transformed the approach to management. In this review we will discuss the current understanding of the pathophysiology of HAE, diagnostic evaluation of recurrent angioedema without urticaria, and the therapeutic approach to HAE. We advocate taking an integrative approach to care in order to normalize the lives of affected patients.

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Escalating Doses of C1 Esterase Inhibitor (CINRYZE) for Prophylaxis in Patients With Hereditary Angioedema

Cited by 50 publications

References 12 publications

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

Efficacy and Safety of an Intravenous C1-Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary angioedema

How we manage persons with hereditary angioedema

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