Nonfactor Therapies for Hemophilia

Young, Guy

doi:10.1097/hs9.0000000000000911

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…Research and development strategies over the past decades have focused on novel EHL concentrates and non‐factor therapeutics for the treatment of haemophilia as well as gene therapy 11,12,33–36 . EHL products utilizing molecular modifications to the FVIII or FIX protein to prolong circulatory half‐life have been successful in decreasing the frequency of infusions in HB to once every 1−2 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…The use of BPAs in patients with inhibitors added to the treatment burden, as these agents have less haemostatic efficacy than FVIII or FIX concentrates in the non‐inhibitor setting and thus drove much of the early innovation. Non‐factor therapy products can often be given subcutaneously and include both FVIIIa mimetics and rebalancing agents 11 . Rebalancing agents are potential options for both HA and HB with and without inhibitors while the FVIIIa mimetics are limited to HA with and without inhibitors 38 .…”

Section: Discussionmentioning

confidence: 99%

“…Fitusiran prophylaxis was associated with notable side effects including hepatotoxicity (24% of subjects), gallbladder disease (15% of subjects), and vascular thrombosis (5% of subjects) 60 . A full review of additional rebalancing agents not yet approved is beyond the scope of this article but briefly additional agents targeting TFPI as well as activated protein C and protein S are being investigated 11,12,59 . These novel therapies promise significantly improved prophylaxis for PWHBI which will change conversations around inhibitor management.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibitors also occur in 5%−10% of those with severe haemophilia B (HB) exposed to factor IX (FIX) concentrates 10 . Other novel therapies, including rebalancing agents, will likely dramatically change the landscape for HB with inhibitors and join the toolbox for HA 11,12 . This review discusses how inhibitors fit into the changing landscape.…”

Section: Introductionmentioning

confidence: 99%

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Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Meeks,

Zimowski

2024

Haemophilia

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IntroductionThe advent of therapeutic recombinant factor VIII (FVIII) and factor IX (FIX) protein infusions revolutionized the care of persons with haemophilia in the 1990s. It kicked off an era with the increasing use of prophylactic factor infusions for patients and transformed conversations around the ideal trough activity levels as well as the ultimate goals in tailored, individualized care. Our knowledge surrounding the immunologic basis of inhibitor development and treatment derives from a time when patients were receiving frequent factor infusions and focused on immune tolerance induction following inhibitor development.DiscussionMore recently, care was revolutionized again in haemophilia A with the approval of emicizumab, a bispecific antibody mimicking activated FVIII function, to prevent bleeding. The use of emicizumab prophylaxis has resulted in a significantly slower accumulation of factor exposure days and continued effective prophylaxis in the case of inhibitor development. While emicizumab is effective at reducing the frequency of bleeding events in patients with haemophilia A, management of breakthrough bleeds, trauma, and surgeries still requires additional treatment. Ensuring that FVIII is a therapeutic option, particularly for life‐threatening bleeding events and major surgeries is critical to optimizing the care of persons with haemophilia A. Other novel non‐factor concentrate therapies, including rebalancing agents, will dramatically change the landscape for persons with haemophilia B with inhibitors.ConclusionThis review discusses the changing landscape regarding the timing of inhibitor development and management strategies after inhibitor development, stressing the importance of education across the community to continue to vigilantly monitor for inhibitors and be prepared to treat persons with inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Meeks,

Zimowski

2024

Haemophilia

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“…More recently, non‐factor replacement therapies 37 including emicizumab, a bispecific monoclonal antibody, led to greater patient satisfaction and reduced prophylactic treatment burden given its infrequent, subcutaneous administration in patients with factor VIII deficiency with or without an inhibitor 38 …”

Section: Prevention and Management Of Haemophilic Arthropathymentioning

confidence: 99%

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations

Bakeer,

Saied,

Gavrilovski

et al. 2024

Haemophilia

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Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores. Point‐of‐care ultrasound is emerging as a safe, cost‐effective, and readily available tool for acute determination of musculoskeletal abnormalities, serial evaluation of joints for sonographic markers of haemophilic arthropathy, and in providing objective insight into the efficacy of new therapies. In acute haemarthrosis, arthrocentesis expedites recovery and prevent the vicious cycle of bleed‐synovitis‐rebleed. When synovial proliferation develops, a multidisciplinary team approach is critical with haematology, orthopaedics, and physiotherapy involvement. Synovectomy is considered for patients with chronic synovitis that fail conservative management. Non‐surgical and minimally invasive procedures should always be offered and considered first. Careful patient selection, screening and early intervention increase the success of these interventions in reducing bleeding, pain, and improving joint function and quality of life. Chemical synovectomy is practical in developing countries, but radioactive synovectomy appears to be more effective. When surgical synovectomy is considered, arthroscopic/minimally invasive approach should be attempted first. In advanced haemophilic arthropathy, joint replacement and arthrodesis can be considered. While excited about the future of haemophilia management, navigating musculoskeletal challenges in the aging haemophilia population is equally important.

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Perioperative Management of Hemophilia Patients

Lowell,

Calgi,

Caruso

et al. 2024

Curr Anesthesiol Rep

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Purpose of Review Hemophilia is a rare, typically inherited, condition where a specific clotting factor is reduced or even near absent. Patients with hemophilia who present for an invasive procedure, whether elective or urgent, are at increased risk of bleeding intraoperatively and postoperatively. Recent Findings Ten years ago, most patients with hemophilia with moderate or severe disease were treated with standard half-life factor replacement therapy, either prophylactic or on-demand. Now, patients may present on extended half-life factor therapy, or on a non-factor hemostatic therapy, or as a recipient of gene therapy. Further complicating the challenge of caring for these patients is that most of these new modalities will typically require supplementation with traditional factor therapy when surgery is required. Summary An in-depth understanding of all the potential treatment options for hemophilia is essential when anesthesiologists care for a patient with hemophilia. And there are several perioperative arenas (neuraxial procedures, point-of-care coagulation tests such as ROTEM or TEG, and cardiopulmonary bypass) where hemophilia creates unique considerations.

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Nonfactor Therapies for Hemophilia

Cited by 10 publications

References 17 publications

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations

Perioperative Management of Hemophilia Patients

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