Researchers Recommend Changes to Protocol in Novoseven/Feiba Combo Therapy

Combining the bypassing agents Novoseven and Feiba, with extended time between doses, could be a successful and cost-effective protocol to manage bleeding episodes in hemophilia A patients with inhibitors, according to a retrospective study.

The study, “Combination of Novoseven and Feiba in hemophiliac patients with inhibitors,” was published in Open Medicine.

Hemophilia A is a genetic disorder caused by a missing or defective clotting factor VIII (FVIII) in the blood. The lack of FVIII leads to bleeding episodes.

The first line of treatment is replacement therapy, in which a modified version (called recombinant) of FVIII is administered either as prophylaxis, to prevent bleeding episodes, or to control occurring bleeding episodes.

However, around 30 percent of patients with severe hemophilia A develop inhibitors — antibodies that attack the lab-made FVIII, rendering the replacement therapy ineffective.

Bypassing agents are the treatment of choice for patients with inhibitors because they achieve clotting using routes of healing that do not depend on FVIII, thus avoiding the necessity of the missing factor.

However, bypassing agents are costly and not as effective as replacement therapies, so protocols to manage the bleeding episodes that reduce costs without increasing the risks to the patient are needed.

A group of researchers at the Hacettepe Hematology Department in Turkey performed a retrospective study to evaluate the efficacy of two bypass agents to manage bleeding episodes in hemophilia A patients with inhibitors.

They evaluated the recombinant factor VIIa Novoseven (distributed by Novo Nordisk), the activated prothrombin complex concentrate Feiba (distributed by Shire, part of Takeda), and a combination of both.

Five patients who had 19 bleeding episodes between 2008 and 2016 were evaluated. The median age was 40 years old (ages 28-78). Four patients had severe hemophilia A and one had the mild form of the disease.

The bleeding episodes were caused by tooth extraction, surgeries, and hematomas in places such as knees and elbows.

Eleven bleeding episodes were treated with Feiba, five with Novoseven, and three with the combination. The treatments lasted between one and 14 days depending on the clinical condition and the level of bleeding, and were successful in all but one patient, who was later stabilized.

“We have evaluated our clinic’s data about hemophilia A patients with inhibitors, and we offer a different protocol in the management of bleeding episodes for these patients,” the authors wrote.

“We offer to use [Novoseven during the] first three days and then switching to [Feiba] with a different dosing protocol, which offers us a safer, cheaper, and flexible control of the bleeding.”

The use of Novoseven is recommended during the first three days because the half-life of Feiba is shorter and the risk of bleeding between doses at the beginning is high.

However, because Novoseven is more expensive, the authors recommend switching to Feiba after reducing the risk of bleeding. This way, the protocol cuts the cost of treatment without increasing the risk of bleeding.

The use of the two agents at the same time was more effective than the separate treatments, but it increased the risk of thrombosis and clots, so it is only recommended in cases of life-threatening bleeding.

The authors recommended that the time between doses of the agents be extended, as this would allow more flexibility in the treatment protocol.

“This modification lets us control the drug costs without facing extra complications or bleeding risks. To conclude, in this paper we have evaluated our clinic’s data about hemophilia A patients with inhibitors and we offer a different protocol in the management of bleeding episodes for these patients,” they stated.