Prophylaxis is not just for kids anymore. With the US Food and Drug Administration’s (FDA’s) approval of Kogenate®, Bayer HealthCare’s recombinant drug for routine prophylaxis, for adults on May 12, 2014, adult patients with hemophilia A and their hematologists have a new option for preventing bleeds.
FDA approval of Kogenate for adults was based on Secondary Prophylaxis in Adults, a Randomized Trial (SPINART), a clinical trial of 84 men ages 15–50 with severe hemophilia A (<1% factor VIII). Results of the study, published in the Journal of Thrombosis and Haemostasis in 2013, showed the significant difference in bleeding episodes between the men receiving prophylaxis three times weekly vs. those treating on demand (as needed). Men in the on-demand group experienced 15.2 times more bleeds than those in the prophylaxis group. Further, 22 of the 42 men on prophylaxis had no bleeds during the trial. The most frequent side effects were inhibitor formation in previously untreated and minimally treated patients, skin rash and itching, pain and inflammation at the infusion site. Infections in central venous access devices also occurred.
By now the advantages to prophylaxis are proven, at least in children. “I don’t think anyone would dispute that a benefit of being on prophylaxis is bleed frequency reduction,” says Nigel Key, MB, ChB, FRCP, director of the University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center. When to switch adults to a prophylaxis regimen varies by hemophilia treatment center (HTC), says Key. He considers development of a target joint or multiple bleeds into different joints or muscles as precursors to adult prophylaxis. “In my own practice, if bleeds are approaching one a month, I would recommend it,” he says.
The ability of prophylaxis to slow joint disease progression in adults, while presumed to be the case, has not been well documented in the literature, says Key. “There’s still room for additional research and having good end points of joint health that we all can agree on in adults,” he says.
Barriers to adult prophylaxis
Survey results from 71 HTCs, published in Haemophilia in 2012, showed that of the 2,232 adults (ages 18–65 and older) with severe hemophilia A, 17% were on primary prophylaxis. In contrast, 37% of children with severe hemophilia A in the study were on prophylaxis.
Men who treat bleeds after they occur, rather than preventively, sometimes would rather fight than switch. “I’m often struck by the patient’s own reluctance to go on prophylaxis, even when the usual issues that we deal with in my state, like insurance and so on, are not a barrier,” Key says. After popping the prophylaxis question at several clinic visits, the patient still may not change. “It can be a culture shift to say you’re going to have to do this two to three times a week to prevent bleeds.”
The Haemophilia study found that education can be a barrier, no matter the regimen. Nearly 80% of respondents didn’t understand the benefits of adherence; 67% denied or lacked acceptance of the consequences of not sticking to a treatment regimen. The study further documented that the older the patient, the greater the use of on-demand therapy.
Chronic joint pain from arthritis should not necessarily improve as a result of prophylaxis, but in some patients it does, says Key. “So, it’s not just the frequency of demonstrable bleeds that matters,” he says. These patient-reported outcomes need to be included in more studies, he says. “There’s an educational issue for patients, where really good data on adult prophylaxis would be nice.”
Support from adult hematologists is also vital for adult prophylaxis success. Some treaters are conservative in initiating prophylaxis in adults or following up with patients. “If they’re not committed, the patient isn’t going to do it,” Key says.