Systematic Review of Randomized Controlled Trials of Prophylactic Clotting Factor Concentrate in Hemophilia.

Abstract Introduction: One of the current approaches to managing persons with hemophilia entails the use of prophylactic treatment with clotting factor concentrates (CFC) to prevent bleeds and bleeding related complications. However, this process is not practiced in all countries, or is based on the synthesis of evidence from data of all trials. Objective: To conduct a systematic review/meta-analysis (SR/MA) regarding the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B. Methods: We conducted a SR of all randomized controlled trials (RCTs) that studied the effect of prophylactic CFCs in people with hemophilia A or B. We searched all major electronic databases (MEDLINE, LILACS, EMBASE, and the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Controlled Trials Register) as well as performing handsearches of journals and relevant meeting abstract books. We included RCTs that that compared the use of prophylactic CFCs to a control group. Results: We identified 29 studies, of which four (including 37 participants) were eligible for inclusion. Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) −10.80 (95% confidence interval (CI) −16.33 to −5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD −5.04 (95%CI −17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD −0.14 (95% CI −1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD −3.30 (95% CI −5.50 to − 1.10) bleeds per year. Conclusion: There is insufficient evidence to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates.