Thalidomide for the treatment of gastrointestinal bleeding due to angiodysplasia in a patient with Glanzmann’s thrombasthenia

Angiodysplasia is a frequent cause of persistent gastrointestinal (GI) hemorrhage in elderly patients. Although GI bleeding isn’t the most common manifestation in patients with bleeding disorders, when present, it represents a challenging complication. We describe a 62-year-old patient with Glanzmann’s thrombasthenia, who used thalidomide for severe and recurrent GI bleeding. For 6 months, the patient experienced temporary control of GI bleeding with thalidomide in a daily oral dose of 100 mg. The anti-angiogenic effects of thalidomide have recently been explored by several groups, particularly in the management of bleeding from angiodysplasia, including cases with von Willebrand disease. Here, we review the relevant descriptions of the use of thalidomide in this situation, and also discuss potential reasons why we observed only a temporary control of the GI bleeding in our patient, such as the use of low-dose regimen due to limitations posed by thalidomide side effects

Musculoskeletal evaluation in severe haemophilia A patients from Latin America

There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL−1) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long‐term prophylaxis. Overall, 143 patients (5–66 years of age) were enrolled from nine countries. In countries where long‐term prophylaxis had been available for at least 10 years (Group A), patients aged 5–10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long‐term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long‐term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated

Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (on-demand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the long-term safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks

Updates From Guardian (tm): A Comprehensive Registration Programme

Turoctocog alfa is an approved B-domain truncated recombinant factor VIII concentrate for adults and children with haemophilia A. Clinical data for turoctocog alfa have been reported from the guardian1, guardian2 and guardian3 phase III trials. guardian1 and guardian3 phase III trials enrolled 150 adolescents/adults (12yr), and 63 children (200 patients treated for a cumulative total of >54000 exposure days in the phase III trials. Pooled efficacy data show a favourable long-term effect of turoctocog alfa on annualised bleeding rate and a success rate for haemostatic response of 86%; 90% of bleeds were resolved with 1-2 doses. This article reviews the clinical development of turoctocog alfa with reference to the guardian clinical programme, describing results obtained to date and ongoing trials.95812229Novo Nordisk Health Care AG (Zurich, Switzerland

Updates from guardian™: a comprehensive registration programme

Turoctocog alfa is an approved B‐domain truncated recombinant factor VIII concentrate for adults and children with haemophilia A. Clinical data for turoctocog alfa have been reported from the guardian™1, guardian™2 and guardian™3 phase III trials. guardian™1 and guardian™3 phase III trials enrolled 150 adolescents/adults (≥12 yr), and 63 children (200 patients treated for a cumulative total of >54 000 exposure days in the phase III trials. Pooled efficacy data show a favourable long‐term effect of turoctocog alfa on annualised bleeding rate and a success rate for haemostatic response of 86%; 90% of bleeds were resolved with 1–2 doses. This article reviews the clinical development of turoctocog alfa with reference to the guardian™ clinical programme, describing results obtained to date and ongoing trials95S81Special Issue: 12th Novo Nordisk Symposium on Haemostasis Management, Vienna, Austria, 4–6 June 201422Medical writing support was provided by Andy Lockley of Bioscript Medical Ltd (Macclesfield, UK) and funded by Novo Nordisk Health Care AG (Zurich, Switzerland

Gene therapy: paving new roads in the treatment of hemophilia

Hemophilia is a monogenic disease with robust clinicolaboratory correlations of severity. These attributes coupled with the availability of experimental animal models have made it an attractive model for gene therapy. The road from animal models to human clinical studies has heralded significant successes, but major issues concerning a previous immunity against adeno-associated virus and transgene optimization remain to be fully resolved. Despite significant advances in gene therapy application, many questions remain pertaining to its use in specific populations such as those with factor inhibitors, those with underlying liver disease, and pediatric patients. Here, the authors provide an update on viral vector and transgene improvements, review the results of recently published gene therapy clinical trials for hemophilia, and discuss the main challenges facing investigators in the field457743750sem informaçãosem informaçãoDr. Yamaguti-Hayakawa reports personal fees and non-financial support from Roche outside the submitted work. Dr. Ozelo reports grants from BioMarin, Pfizer, during theconduct of the study and grants from Novo Nordisk, Shire,Bioverativ, and Roche outside the submitted wor

Haemophilia experiences, results and opportunities (HERO study) in Brazil : assessment of the psychosocial effects of haemophilia in patients and caregivers

The international Haemophilia Experiences, Results and Opportunities (HERO) study assessed the psychosocial aspects of life for people with haemophilia (PWH) and their caregivers in several countries. Brazil was not included in this initiative. An observational, multicentre, cross-sectional study was performed involving PWH (moderate-to-severe haemophilia) and their caregivers, from November 2014 to July 2015. The primary objective was to quantify the extent of the primary psychosocial factors affecting PWH in their everyday life. Descriptive statistics and comparisons between Brazilian and global respondents are presented. A total of 100 adult male PWH and 100 caregivers (responding on behalf of their oldest affected child aged <18 years) completed the survey. Sixty-eight per cent of the PWH had haemophilia A without inhibitors. Chronic pain and hepatitis C were the most common conditions related to haemophilia. On the EQ-5D assessment, 64% of PWH reported extreme/moderate pain. Treatment for depression or anxiety was reported by 18% of PWH and by 29% of caregivers. There was a lower employment rate for PWH in Brazil, compared to the countries included in the original HERO survey (51% vs 60%); 71% of PWH stated that haemophilia has a negative impact on their work. Over the previous 5 years, 58% of PWH and 68% of caregivers did not have difficulties in obtaining the concentrated factor for treatment. Our study presents an overview of the psychosocial aspects of life with haemophilia in Brazil, providing a basis for health policy decisions and may further improve comprehensive care for PWH254640650GF is the author of the study protocol and responsible for reporting the results. CL and MO were the principal investigators. CL, RB, GF and MO interpreted data and reviewed the manuscript. All authors read and approved the final version of the paper. Cristiane Aoqui Guenoub provided medical writing on behalf of Springer Healthcare. This manuscript was prepared according to the International Society for Medical Publication Professionals' Good Publication Practice for Communicating Company‐Sponsored Medical Research: the GPP3 Guideline