Disease burden and remaining unmet need in patients with haemophilia A treated with primary prophylaxis.

AIMS: There is evidence that people with haemophilia A still experience morbidity and functional limitation due to joint damage despite prophylaxis. This study aimed to compare their quality of life and work-related function with that of the general population and patients with osteoarthritis. METHODS: Data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) database were compared with published data from normative populations and patients with osteoarthritis in Europe and the United States. RESULTS: In the predominantly young (age 18-35 years) adult CHESS population treated with primary prophylaxis, about 30% reported a target joint; the average frequency of bleeds was one per year; half reported chronic pain. Levels of anxiety and depression were similar to those reported by people using on-demand treatment. Employment and productivity were lower than in the general population. The level of presenteeism (attending work with impairment) was comparable with that reported for a much older population with osteoarthritis who had more extensive joint damage and greater prevalence of pain. CONCLUSION: Compared with the general population, clinical outcomes and quality of life are indicated to be impaired for young adults whose haemophilia is managed by primary prophylaxis. Primary prophylaxis is not associated with lower levels of anxiety and depression than on-demand treatment, and pain is common. The level of presenteeism is comparable to that reported in people with osteoarthritis, an older population with more joint disease. Further studies are needed to fully assess the implications of compromised work performance among young adults with haemophilia as they seek to build a career.

Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial.

Objectives: To compare the efficacy of emicizumab prophylaxis with that of factor VIII (FVIII) prophylaxis in patients with hemophilia A without inhibitors using two approaches: network meta-analyses (NMA) and additional sub-group analyses from the HAVEN 3 trial.Methods: The NMA used data from trials identified using a systematic literature review and compared bleed rates in patients receiving emicizumab prophylaxis and patients receiving FVIII prophylaxis using a Bayesian, random effects generalized linear model with log link Poisson likelihood. Additional sub-groups of the HAVEN 3 trial included here were defined as patients whose dose-taking behavior met either European label or World Federation of Hemophilia guidelines. A negative binomial regression model was used to conduct an intra-patient comparison of bleed rates within the sub-groups, during treatment with FVIII prophylaxis before entering HAVEN 3 and treatment with emicizumab prophylaxis during HAVEN 3.Results: Four studies were included in the base-case NMA. Evidence showed that the total treated bleed rate was lower with emicizumab prophylaxis compared with FVIII prophylaxis (rate ratio [RR] = 0.36 [95% credible interval (CrI) = 0.13-0.95]). Similar associations were observed in sensitivity analyses. The additional HAVEN 3 analyses also showed lower rates of treated bleeds with emicizumab prophylaxis than with FVIII prophylaxis (RRs [95% confidence interval (CI)] = 0.380 [0.186-0.790] and 0.472 [0.258-0.866] in two sub-groups). These results confirm the original HAVEN 3 intra-patient comparison findings.Conclusions: Combined findings from NMA and additional sub-group analyses of HAVEN 3 support the superiority of emicizumab prophylaxis over FVIII prophylaxis in patients with hemophilia A without inhibitors.