Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Annualized bleeding rate was reduced by 91% in the fitusiran prophylaxis group compared to the bypassing agents on-demand group.

2. 5% of patients in the fitusiran group reported thromboembolic events; there were no deaths.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Hemophilia is marked by a deficiency in certain coagulation factors that make patients prone to bleeding. Prophylaxis is the standard of care in these patients but is often complicated by the need for frequent transfusions and loss of intravenous access. Fitusiran is a novel small interfering RNA that may regulate hemostasis through the inhibition of antithrombin synthesis, although its use in hemophilia patients is not well known. This randomized controlled trial aimed to compare the safety and efficacy of fitusiran in patients with hemophilia A and hemophilia B with inhibitors. The primary outcome was the mean annualized bleeding rate while key secondary outcomes included joint and spontaneous bleeding rate and mobility concerns. According to study results, patients in the fitusiran group reported significantly reduced bleeding events and greater hemostatic efficacy compared to the bypassing agents on-demand group. Although this study was well done, it included a small sample size with a 2:1 randomization in favor of the intervention group. Additionally, excluding patients with less than 60% antithrombin activity may reduce the generalizability of these results to other patients with hemophilia.

In-depth [randomized-controlled trial]:

Between Feb 14, 2018, and Jun 23, 2021, 85 patients were screened for eligibility across 26 sites in 12 countries. Included were male patients aged ≥ 12 years with hemophilia A or hemophilia B and ≥ 6 bleeding episodes in the past 6 months. Participants with lower than 60% antithrombin activity were excluded. The primary outcome of mean annualized bleeding was significantly lower in the fitusiran prophylaxis group (1.7, 95% confidence interval [CI] 1.0-2.7) compared to the bypassing agents on-demand group (18.1, 95% CI 10.6-30.8), denoting a 91% reduction in bleeding (p<0.0001). Substantially more patients in the fitusiran group (66%) had zero treated bleeds compared to the latter (5%). The majority of adverse events were mild-to-moderate with elevated liver enzymes in 32% and thromboembolic events in 5% of patients in the fitusiran group. There were no treatment-related fatalities. Findings from this study suggest that prophylaxis with fitusiran significantly reduces bleeding among hemophilia patients and may improve clinical outcomes.

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