Inmaculada Martinez-Saguer

C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis.

BACKGROUND: Hereditary angioedema (HAE) caused by functional deficiency of C1‐inhibitor (C1‐INH) is a rare disease that manifests with recurrent spontaneous nonallergic edema of the subcutaneous tissues and mucous membranes. In cases of laryngeal edema that are not treated immediately, HAE is associated with high mortality rates. Attenuated androgens (e.g., danazol) are usually administered for prophylaxis, but associated side effects may limit their use. This study investigated the efficacy, safety, and quality of life (QoL) associated with a pasteurized plasma‐derived C1‐inhibitor (pC1‐INH) concentrate for individual replacement therapy (IRT) in patients with severe HAE suffering from frequent attacks who were intolerant or not responding to danazol.

Home therapy with intravenous human C1-inhibitor in children and adolescents with hereditary angioedema

BACKGROUND: C1‐esterase inhibitor (C1‐INH) replacement therapy is the treatment of choice for acute edema attacks in patients with hereditary angioedema (HAE).

Hereditary angioedema (HAE) in children and adolescents—a consensus on therapeutic strategies

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.

Epidemiology of Inhibitors in Haemophilia A

One of the most serious complications of the treatment of haemophilia A is the development of inhibitors. Former studies mostly considered the prevalence of inhibitor development, thus underestimating its true risk. Prevalences ranged widely (7–18%) probably due to the populations studied and the study design. Recent prospective previously untreated patients (PUP) studies were more comparable because of similar study designs. Eight PUP studies regarding the incidence of factor VIII inhibitors were analyzed: The inhibitor incidences (Independent of severity of haemophilia) ranged from 18.4 to 28%. Evaluating only severe haemophiliacs (factor VIII<2%) significantly higher incidences were found. After 9–36 exposure days (as medians inhibitor development occurred at 0.8‐3.3 years of age (as medians).

Pharmacokinetic analysis of human plasma―derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life‐threatening disease presenting with acute edema of subcutaneous tissues and/or mucous membranes. Patients with HAE have abnormally low or dysfunctional C1‐inhibitor (C1‐INH). Preventing the progression of acute attacks is the main goal of C1‐INH replacement therapy; knowledge of the C1‐INH concentrate half‐life is of crucial importance. This pharmacokinetic study was conducted to investigate the pharmacokinetics of pasteurized human plasma–derived C1‐INH concentrate (pC1‐INH).

Characterization of acute hereditary angioedema attacks during pregnancy and breast-feeding and their treatment with C1 inhibitor concentrate

OBJECTIVE The objective of the study was to investigate the rates and characteristics of hereditary angioedema (HAE) attacks associated with pregnancy, delivery, and the postpartum period and their treatment with C1 esterase inhibitor (INH) concentrate. STUDY DESIGN This was an observational study including 22 women with type I HAE, with data collected before, during, and after 35 pregnancies (37 children) based on patient diaries, interviews, and case report forms. RESULTS In 83% of pregnancies, attack rates increased during pregnancy; highest mean rates occurred in the second and third trimesters. C1-INH concentrate effectively controlled attacks and was safe for mothers and children. Low-plasma C1-INH activity during pregnancy tended to be associated with an increased chance of giving birth to a child with HAE. CONCLUSION Increased attack rates during pregnancy in women with HAE are well controlled with C1-INH concentrate, indicating the clear benefit of integrating the availability of C1-INH concentrate into the management plan for these women during pregnancy and delivery.

On demand treatment and home therapy of hereditary angioedema in Germany - the Frankfurt experience

BackgroundManifestation of acute edema in hereditary angioedema (HAE) is characterized by interindividual and intraindividual variability in symptom expression over time. Flexible therapy options are needed.MethodsWe describe and report on the outcomes of the highly individualized approach to HAE therapy practiced at our HAE center in Frankfurt (Germany).ResultsThe HAE center at the Frankfurt University Hospital currently treats 450 adults with HAE or AAE and 107 pediatric HAE patients with highly individualized therapeutic approaches. 73.9% of the adult patients treat HAE attacks by on-demand therapy with pasteurized pd C1-INH concentrate, 9.8% use additional prophylaxis with attenuated androgens, 1% of the total patient population in Frankfurt has been treated with Icatibant up to now. In addition adult and selected pediatric patients with a high frequency of severe attacks are instructed to apply individual replacement therapy (IRT) with pasteurized pd C1-INH concentrate. Improvement on Quality of Life items was shown for these patients compared to previous long-term danazol prophylaxis. Home treatment of HAE patients was developed in the Frankfurt HAE center in line with experiences in hemophilia therapy and has so far been implemented over a period of 28 years. At present 248 (55%) of the adult patients and 26 (24%) of the pediatric patients are practicing home treatment either as on demand or IRT treatment.ConclusionsIn conclusion, the individualized home therapies provided by our HAE center, aim to limit the disruption to normal daily activities that occurs for many HAE patients. Furthermore, we seek to optimize the economic burden of the disease while offering a maximum quality of life to our patients.

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1‐INH‐HAE.

Review of recent guidelines and consensus statements on hereditary angioedema therapy with focus on self-administration.

Consensus meetings and the resulting recommendations shape treatment choices in rare diseases such as hereditary angioedema (HAE) because they combine the experience of prescribing physicians and the patients who are receiving therapy. Self-administration of HAE therapy was recognised as a potential treatment option in the first consensus publication in 2003. Recent studies have confirmed that self-administration of therapy resolves attacks quickly, safely and minimises burden of disease; however, the discovery of inconsistent treatment approaches is a concern and warrants investigation into the barriers that prevent adherence with current recommendations.

Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1‐inhibitor concentrate

Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long‐term prophylaxis with twice‐weekly intravenous injections of plasma‐derived C1‐inhibitor (pdC1‐INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1‐INH has not been studied in patients with HAE.