Search

Background: Patient-reported outcomes (PROs) reflect patient perceptions of disease and treatment and are important for evaluating new therapies. Objectives: Evaluate the effects of once-daily concizumab prophylaxis on health-related quality of life (HRQoL), treatment burden, and treatment preference in males aged ≥12 years with hemophilia A/B with inhibitors. Methods: Patients enrolled in the multicenter, open-label explorer7 phase 3 study (ClinicalTrials.gov identifier: NCT04083781) were randomized to receive no prophylaxis (arm 1) or concizumab prophylaxis (arm 2) or were nonrandomly allocated to concizumab prophylaxis (arms 3 and 4). The study included questionnaires to assess patients’ perception of HRQoL (Haemophilia Quality of Life Questionnaire for Adults), treatment burden (Hemophilia Treatment Experience Measure), and treatment preference (Haemophilia Patient Preference Questionnaire). Results: The estimated treatment difference between patients receiving concizumab prophylaxis vs no prophylaxis at week 24 for Haemophilia Quality of Life Questionnaire for Adults “total score” was −22.6 points (95% CI, −42.5; −2.7), directionally favoring patients receiving concizumab prophylaxis. For Hemophilia Treatment Experience Measure “total score,” the estimated treatment difference was −19.9 points (95% CI, −34.3, −5.6) in favor of concizumab vs no prophylaxis. The majority of patients receiving concizumab expressed a preference for concizumab over their previous treatment, the main reasons being “fewer bleeds,” “require less time,” and “less painful to inject.” Across all PROs, there were less responses collected than anticipated, limiting interpretations. Conclusion: PROs collected during the explorer7 study showed improvements in some domains of HRQoL, treatment burden, and patient treatment preference in persons with hemophilia A or B with inhibitors receiving concizumab prophylaxis compared with no prophylaxis.

Introduction: Concizumab is a humanised, recombinant monoclonal antibody administered to patients with haemophilia A/B with inhibitors (HAwI/HBwI) as a once-daily prophylaxis (PPX) in the phase 3 explorer7 study (NCT04083781). In the primary analysis, concizumab PPX reduced the annualised bleeding rate for patients with HAwI/HBwI. Subcutaneous (SC) administration of concizumab may contribute to a lower treatment burden compared to intravenous factor replacement therapy. Here, we present data from explorer7 on patient-reported treatment burden and patient preference. Methods: A total of 133 patients aged ≥12 years were either randomised 2:1 to concizumab PPX (arm 2; n = 33) or no PPX (arm 1; n = 19) or assigned to non-randomised concizumab PPX (arms 3 or 4; n = 81). Patients could complete the Hemophilia Treatment Experience Measure (Hemo-TEM) questionnaire at baseline (Week 0) and Week 24 and the Haemophilia Patient Preference Questionnaire (H-PPQ) at Week 24. Analysis of covariance was applied to estimate mean change in Hemo-TEM domain and total scores from baseline to Week 24. The H-PPQ results were analysed descriptively. Results: The Hemo-TEM total score improved with concizumab PPX (n = 19) from baseline to Week 24 (mean estimate -17.0 points [95% CI: -23.7; -10.3]), but not in patients with no PPX (n = 6, mean estimate 3.0 points [95% CI: -9.4; 15.3]). The estimated treatment difference in Hemo-TEM total score between both arms was statistically significant (-19.9 points [95% CI: -34.3; -5.6]; p = 0.009). Significant improvements in arm 2 were observed in the domains “injection difficulties”, “interference”, and “emotional impact”. In the H-PPQ questionnaire; 77/99 patients (78%) preferred concizumab over their previous treatment, while only one patient (1%) preferred their previous treatment (16 patients did not respond, and 5 patients had no preference). Of all responding patients, 93% preferred concizumab with the 3 main reasons being “fewer bleeds”(75%), “require less time”(43%), and “less painful to inject”(33%). Discussion/Conclusion: A lower treatment burden was observed for daily concizumab PPX with better Hemo-TEM domain and total scores. Lower treatment burden due to SC administration combined with reduced bleeding (especially in HBwI) resulted in a clear patient preference in favour of concizumab over their previous treatment.

Objective: An integrated analysis based on the Phase 2 TITAN (NCT01151423) and Phase 3 HERCULES (NCT02553317) studies with caplacizumab (CPLZ) in acquired thrombotic thrombocytopenic purpura (aTTP) was performed to assess treatment differences on efficacy and safety outcomes that may have been undetected in the individual trials. Methodology: In both trials, patients with an acute episode of aTTP were randomized to receive CPLZ or placebo (PBO) in addition to therapeutic plasma exchange (TPE) and immunosuppression. All randomized patients from both studies were included in the integrated efficacy analyses (CPLZ: n=108; PBO: n=112), and those who received at least 1 dose of the study drug were included in the safety analyses (CPLZ: n=106; PBO: n=110). Results: CPLZ significantly reduced mortality (0 vs 4 deaths; P

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors’ clinical experience in treating patients with AHA.

Paul N KnoeblDepartment of Medicine 1, Division Hematology and Hemostasis, Medical University of Vienna, Vienna, AustriaAbstract: The protein C pathway has an important function in regulating and modulating blood coagulation and ensuring patency of the microcirculation. Protein C deficiency leads to macro- and microvascular thrombosis. Congenital severe protein C deficiency is a life-threatening state with neonatal purpura fulminans and pronounced coagulopathy. Patients with heterozygous protein C deficiency have an increased risk for thromboembolic events or experience coumarin-induced skin necrosis during initiation of coumarin therapy. Replacement with protein C concentrates is an established therapy of congenital protein C deficiency, resulting in rapid resolving of coagulopathy and thrombosis without reasonable side effects. This article summarizes the current knowledge on protein C replacement therapy in congenital protein C deficiency.Keywords: protein C, deficiency, replacement therapy, purpura fulminans, coagulopathy