OC 43.2 - Low-dose Emicizumab prophylaxis in severe hemophilia A patients – a pilot study with a much anticipated promise for a resource limited country

Background: Prophylaxis is the standard-of-care for persons with hemophilia(PwH) reducing the annual bleed-rate(ABR) from 8-15 to 0-1.However, only 4-9% PwH are on prophylaxis in India. Low-dose CFC prophylaxis has been studied in China, India, Tunisia,etc. showing significant reduction in ABR from 7 to 0.5. However, long term outcomes of low-dose prophylaxis showed average ABR and target-joints were persistent.
Emicizumab(EC) prophylaxis has shown an excellent efficacy in HAVEN1-4 studies.However, majority of the PwH in developing countries have no access to EC due to very high cost.

Aims: To assess the efficacy of low-dose EC prophylaxis(3mg/kg monthly) in comparison to standard-dose EC and low-dose FVIII prophylaxis(10-20IU/kg twice a week) and to compare the cost of these treatments.

Methods: A total of 10 PWH(age:3.5-12 yrs); 5 with inhibitors(4-15BU/ml) were initiated on low-dose EC prophylaxis; 4 PWH on standard-dose EC prophylaxis and 10 PWH on low-dose CFC prophylaxis.
Number of bleeds, joint-bleeds, treated-bleeds, target-joints & HJHS joint score were documented; clotting profile was assessed by Non-Activated Thromboelastometry(NATEM-ROTEM). Trough blood plasma EC-levels were assessed by modified one-stage factor assay using r2diagnostic EC calibrator/controls.

Results: ABR, ABJR, treated-bleeds and total target-joints were found significantly reduced(p < 0.0001, 95% CI) when compared to low-dose CFC prophylaxis and equivalent to standard-dose EC prophylaxis.Improvements in HJHS were observed in patients on low-dose and standard-dose EC prophylaxis. Clotting-time and clot-formation time of low-dose EC prophylaxis group was significantly shortened than low-dose CFC prophylaxis group(p < 0.0001,95%CI),and almost equivalent to standard-dose EC prophylaxis. Trough blood plasma EC levels was stable at 50 µg/ml and 26µg/ml in PWH on standard-dose and low-dose EC respectively.

Conclusion(s): Low-dose EC prophylaxis is efficacious to reduce ABR significantly with 100% resolution of joints.Results are comparable to standard EC prophylaxis and better than low-dose CFC prophylaxis.The cost is cheaper than CFC prophylaxis, holding a true promise for a better tomorrow for all our patients.