The current status of prophylactic replacement therapy in children and adults with haemophilia

Ljung, Rolf; Gretenkort, Nadine

doi:10.1111/bjh.13365

Cited by 59 publications

(65 citation statements)

References 76 publications

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“…However, due to short FVIII half‐life, regular intravenous infusions (2‐4 times/wk) are required to maintain protective trough levels and achieve adequate haemostatic coverage . Despite regular FVIII prophylaxis, clinical and subclinical bleeds may occur . Additionally, substantial treatment burden leaves some individuals unable to adhere to treatment demands, leading to suboptimal care.…”

Section: Introductionmentioning

confidence: 99%

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

et al. 2019

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Introduction Prospectively collected real‐world data on bleeds, haemophilia treatment and safety in persons with haemophilia A (PwHA) without factor VIII (FVIII) inhibitors are limited. A global, non‐interventional study (NIS; NCT02476942) prospectively collected real‐world data in PwHA who were treated per local routine clinical practice. Aim Assess annualized bleeding rate (ABR), haemophilia treatment practices and adverse events (AEs) in adult/adolescent PwHA without inhibitors. Methods Eligible participants aged ≥12 years with severe HA without history of inhibitors prospectively collected bleeding and treatment information. Results Ninety‐four participants were enrolled (median [range] age, 34 [12‐76] years) and monitored for a median (range) of 29.8 (12.4‐47.7) weeks. In the episodic (n = 45) and prophylactic (n = 49) treatment groups, respectively, 872/1066 (81.8%) and 151/189 (79.9%), bleeds were treated; ABRs (95% confidence interval) were 36.1 (30.8‐42.3) and 5.0 (3.3‐7.5), respectively, for treated bleeds and 43.1 (36.5‐50.9) and 6.2 (4.2‐9.2), respectively, for all bleeds, and median (interquartile range) ABRs were 31.1 (19.8‐51.6) and 1.9 (0.0‐8.2), respectively, for treated bleeds and 35.3 (21.7‐62.9) and 2.7 (0.0‐9.4), respectively, for all bleeds. Half of the participants on FVIII prophylaxis had relatively high adherence to treatment, using 2.9 and 2.1 median doses/wk of standard and extended half‐life FVIII, respectively. Serious AEs included gastrointestinal polyp haemorrhage and haemarthrosis; the most common AE was viral upper respiratory tract infection. Conclusion PwHA without inhibitors continue to bleed on prophylaxis, consistent with the literature, and require treatment for breakthrough bleeds. This prospective NIS demonstrates the need for more efficacious haemostatic approaches.

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Section: Introductionmentioning

confidence: 99%

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

et al. 2019

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“…The current standard of care is prophylactic factor replacement therapy . The rationale for prophylaxis was the observation that individuals with moderate hemophilia (as little as 1–5% of residual activity) exhibited fewer hemarthroses and were much less likely to develop arthropathy . The hypothesis was that regular infusions of factor concentrates with a goal of maintaining a plasma activity that did not fall below 1–2% would lead to a more moderate clinical phenotype with less joint bleeding and subsequent arthropathy.…”

Section: Introductionmentioning

confidence: 99%

Gene therapy for hemophilia

Pipe

2017

Pediatric Blood & Cancer

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Individuals with the inherited bleeding disorder hemophilia have achieved tremendous advances in clinical outcomes through widespread implementation of prophylactic replacement with safe and efficacious factor VIII and IX. However, despite this therapeutic approach, bleeds still occur, some with serious consequence, joint disease has not been eradicated, and patients have not yet been liberated from the need for regular intravenous infusions. The shift from protein replacement to gene replacement is offering great hope to achieve durable levels of plasma factor activity levels high enough to remove the risk for recurrent joint bleeding. For the first time, clinical trial results are showing promise for "curative" correction of the bleeding phenotype.

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“…Controlled clinical studies in persons with haemophilia (PwH) have confirmed the superior efficacy of prophylactic factor replacement regimens compared to episodic treatment [1,2]. As a result, prophylaxis regimens have been adopted as standard of care in patients with severe disease, significantly reducing bleeding rates and improving joint health in this population [1].…”

Section: Introductionmentioning

confidence: 99%

“…As a result, prophylaxis regimens have been adopted as standard of care in patients with severe disease, significantly reducing bleeding rates and improving joint health in this population [1]. PwH residing in industrialized countries now aim to live a life with little to no bleeding.…”

Section: Introductionmentioning

confidence: 99%

Recognizing the need for personalization of haemophilia patient‐reported outcomes in the prophylaxis era

et al. 2016

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The safety and efficacy of treatment options for patients with haemophilia have significantly improved over the last two decades, particularly with greater utilization of prophylactic approaches. Consequently, it is becoming increasingly difficult to differentiate the treatment benefits of available choices based on standard endpoints such as annualized bleeding rates and joint health scores. Patient-reported outcomes (PROs) have shown limited ability to discriminate between treatment outcomes, in part because of their comprehensive nature; i.e. differences in specific outcomes meaningful to individual patients are masked by a global scoring system based on a fixed set of items, many of which may be unimportant for any given patient. There is a clear need for new outcome measures. Initiatives to develop patient-centric outcomes that capture clinically meaningful change are ongoing. One such approach, goal attainment scaling (GAS), allows patients, in collaboration with a trained clinician, to select goals from a medical condition-specific menu of options and subsequently facilitates quantitative assessment of goal realization. Thus, it is fully personalized and sensitive to small, often idiosyncratic, treatment benefits, such as improvements in functional capacity. In this paper, we present the underlying rationale for GAS and one other novel approach to PRO personalization, and discuss their potential to augment current outcome measures by reliably detecting and quantifying treatment effects in individuals with haemophilia on prophylaxis.

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The current status of prophylactic replacement therapy in children and adults with haemophilia

Cited by 59 publications

References 76 publications

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

Gene therapy for hemophilia

Recognizing the need for personalization of haemophilia patient‐reported outcomes in the prophylaxis era

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