Homoeopathic Management of Severe Haemophilia in Pediatric age group: Twin Case Study

Both the patients were relieved of their other complaints with homoeopathy.

Real-World Rates of Bleeding, Factor VIII Use, and Quality of Life in Individuals with Severe Haemophilia A Receiving Prophylaxis in a Prospective, Noninterventional Study

Regular prophylaxis with exogenous factor VIII (FVIII) is recommended for individuals with severe haemophilia A (HA), but standardised data are scarce. Here, we report real-world data from a global cohort. Participants were men ≥18 years old with severe HA (FVIII ≤ 1 IU/dL) receiving regular prophylaxis with FVIII. Participants provided 6 months of retrospective data and were prospectively followed for up to 12 months. Annualised bleeding rate (ABR) and FVIII utilisation and infusion rates were calculated. Differences between geographic regions were explored. Of 294 enrolled participants, 225 (76.5%) completed ≥6 months of prospective follow-up. Pre-baseline and on-study, the median (range) ABR values for treated bleeds were 2.00 (0–86.0) and 1.85 (0–37.8), respectively; the median (range) annualised FVIII utilisation rates were 3629.0 (1008.5–13541.7) and 3708.0 (1311.0–14633.4) IU/kg/year, respectively; and the median (range) annualised FVIII infusion rates were 120.0 (52.0–364.0) and 122.4 (38.0–363.8) infusions/year, respectively. The median (range) Haemo-QoL-A Total Score was 76.3 (9.4–100.0) (n = 289), ranging from 85.1 in Australia to 67.7 in South America. Physical Functioning was the most impacted Haemo-QoL-A domain in 4/6 geographic regions. Despite differences among sites, participants reported bleeding requiring treatment and impaired physical functioning. These real-world data illustrate shortcomings associated with FVIII prophylaxis for this global cohort of individuals with severe HA.

Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe

Background Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019–2020). All outcomes were summarised using descriptive statistics. Results A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67. Conclusions These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.

Use of Emicizumab in Patients with Hemophilia a with and without Inhibitors: A Single Center Experience

Emicizumab is a humanized bispecific recombinant monoclonal antibody that binds the enzyme factor IXa and the substrate factor X and mimics the function of FVIII. It solved some unmet needs of haemophilia A (HA) treatment, such as regimen (once weekly up to once monthly infusion) and route of administration (subcutaneous). Most importantly, emicizumab reduce bleeding episodes and improved the quality of life of these patients. Emicizumab received FDA approval for prophylaxis in HA patients with inhibitors in November 2017 and for patients without inhibitors in October 2018.The aim of this study is to provide information on treatment with emicizumab in patients with severe haemophilia A with and without inhibitors in terms of efficacy, safety and quality of life. Here we report our experience with 9 patients with severe haemophilia A (5 with inhibitors and 4 without inhibitors) that were switched from replacement therapy to emicizumab prophylaxis. Median age at initiation of treatment was 26.8 years for patients with inhibitors and 18.7 years for those without inhibitors. Median duration of therapy was 12 months for patients with inhibitors and 8 months for those without inhibitors. All patients were started on emicizumab with a loading dose of 3 mg/kg once weekly for 4 weeks followed by a maintenance dose of 1.5 mg/kg once weekly or every two weeks. The mean annual bleeding rates (ABR) in patients without inhibitor prior to emicizumab was 1.5 compared to 0 while on emicizumab prophylaxis. In subjects with inhibitors ABR was 1.8 compared to 0.4 while on emicizumab prophylaxis. Furthermore, no adverse events including thrombotic events occurred in course of emicizumab prophylaxis. Bleeding events in course of emicizumab prophylaxis did not request any treatment with replacement therapy or bypassing agents. The questionnaire evaluating quality of life (HAL v 2.0 - 2015 ITA; pedHAL v 2.0 - 2015 ITA) was administered to the patients before switch to emicizumab and after a follow up of six months. The scores showed a significant improvement in terms of quality of life in course of emicizumab prophylaxis. In conclusion, our experience suggests that emicizumab prophylaxis is safe and improved protection against bleeding and quality of life compared to replacement therapy in patients with severe A haemophilia. Disclosures Di Raimondo: Amgen: Honoraria; Jazz Pharmaceutical: Honoraria; Pfizer: Honoraria; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb: Honoraria; AbbVie: Honoraria.

Prophylactic Treatment of Severe Haemophilia Á Patients with Inhibitors to FVIII with Peglip-FVIII

Background: FVIII replacement therapy is ineffective for severe haemophilia A (HA) patients who develop inhibitors to FVIII. Patients with intractable inhibitors currently require FVIII mimetics and/or bypassing agents to prevent bleeding. PEGylated liposomes (PEGLip) have been shown to protect FVIII from anti-FVIII antibodies in ex-vivo human studies and in combination with FVIII may present an option for the prophylactic treatment of inhibitor patients. Aims: To (a) demonstrate that PEGLip-FVIII administered intravenously (IV) to severe HA patients with history of inhibitors to FVIII enhances their clotting activity, (b) compare the number of bleeding episodes before and after PEG-Lip treatment, and (c) demonstrate that PEGLip-FVIII is well tolerated with no increase in inhibitor titres. Methods: Stage A: Four patients with a history of inhibitors were given single IV injections of PEGLip-FVIII (simoctocog alfa) at a dose of 22mg/kg PEGLip + 35 IU/kg FVIII and assessed for clotting activity at 0 hours (pre-injection) and at 20min, 1, 2, 4, 8, 24 hours, and daily thereafter up to 7 days using Rotational Thromboelastometry. Stage B: Patients received IV injections of PEGLip-FVIII for 6-weeks at a frequency determined by the investigator based on results obtained during Stage A. Inhibitor titres were monitored throughout. Results: Results are shown below. Treatment with PEGLip-FVIII was highly tolerated with no clinically significant changes in inhibitor titres. No Adverse Drug Reactions were reported. The mean frequency of administration of PEGLip-FVIII was every 5.7±1.4 days. The mean number of bleeding episodes reported during Stage B was 0.5±0.9 per month (due to 1 patient) compared with 0.9±0.4 per month recorded during the 24 weeks prior to enrollment. Conclusion: PEGLip-FVIII in inhibitor patients demonstrated efficacy in preventing spontaneous bleeds without increasing inhibitor titres, indicating a novel FVIII-based treatment for this cohort. Planned studies in a larger cohort may confirm our findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.