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Early emicizumab (Hemlibra) prophylaxis alone prevented clinically relevant bleeds in patients with newly diagnosed acquired hemophilia A, while avoiding the infectious complications of immunosuppressive therapy in this vulnerable population, a phase II study showed.

Over 12 weeks of therapy, a high-dose regimen of the factor VIIIa mimetic antibody yielded a low mean breakthrough bleeding rate (0.04 bleeds per patient-week, upper 97.5% CI 0.06), meeting predefined criteria for success, reported Andreas Tiede, MD, PhD, of the Hannover Medical School in Germany, and colleagues in .

In fact, 70% of the 47 patients in the single-arm study had no breakthrough bleeds through 12 weeks, and investigators observed few thromboembolic events, severe infections, and fatalities.

"The consistently low bleeding rates over 12 weeks of prophylaxis confirm the prophylactic activity of emicizumab," wrote Tiede and colleagues. "In addition, they also open the perspective that immunosuppression can be safely postponed in severely ill patients with acquired hemophilia A until they [have] recovered from the initial illness and reached a sufficiently stable health status to take the risks of immunosuppression."

Acquired hemophilia A is a severe bleeding disorder caused by autoantibodies, or inhibitors, that interfere with the activity of factor VIII. Often occurring unexpectedly, the rare disorder can affect individuals of any age, though often turns up in the elderly.

Treatment involves immediate control of acute bleeding with hemostatic medication and long-term elimination of inhibitors through immunosuppressive therapy -- which is associated with toxicity, infectious complications, and mortality in this frail population of patients, explained Tiede and colleagues.

In a , Margaret V. Ragni, MD, MPH, of the University of Pittsburgh Medical Center and Hemophilia Center of Western Pennsylvania, said the strategy employed in the trial "will probably be practice-changing, and adopted into standard care, as it is safe and effective and improves the risk–benefit ratio."

Furthermore, noted Ragni, "none of the group developed thrombotic microangiopathy or drug-related thrombosis, and more importantly, by avoiding immunosuppression for 12 weeks, some patients had natural reduction in inhibitor titers, such that future immunosuppression was averted."

And, she pointed out, none of the four deaths during the study were due to infection.

The was conducted at 16 hemophilia centers in Germany and Austria. The median age of the study population was 76 years. Patients were eligible if they were diagnosed with acquired hemophilia A on the basis of a factor VIII activity of less than 50 IU/dL and a positive factor VIII inhibitor, were bleeding at the time of screening, and had not received immunosuppressive therapy.

Patients received and completed an accelerated high-dose emicizumab loading regimen in the first week (6 mg/kg and 3 mg/kg on days 1 and 2) in order to protect them from bleeds in the early weeks following diagnosis, with emicizumab maintenance dosing (1.5 mg/kg) continued after that until week 12.

Of the 47 patients enrolled, 33 had no bleeding events through 12 weeks, while seven patients (15%) had one bleed, six patients (13%) had two bleeds, and one patient (2%) had three bleeds.

The study was conducted during the pandemic (2021 to 2022), and the most frequently reported adverse events (AEs) reported during the 24-week study period were COVID-related (10 patients). AEs of grade 3 or worse included COVID in two patients, two cases of acute kidney injury, and one stroke.

Starting at week 12 or later, 29 of the patients began receiving immunosuppressive therapy; none had AEs related to immunosuppression, and 14 experienced remission.

Four patients died on study (two from bleeding, one from COVID, and one from cardiac arrest). None of the deaths were considered related to emicizumab.

Authors noted that randomization of emicizumab prophylaxis was not considered ethical due to the severity of the patients' illness and the increasing off-label use of the therapy in hemophilia A.

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