To investigate this, Jiménez-Yuste et al. carried out a retrospective study to identify cases and analyse the efficacy, cost and safety of bypassing agents (aPCC and rFVIIa) as prophylaxis for patients with haemophilia and inhibitors . In total, 10 patients with severe haemophilia A and inhibitors [median age 4 years (range 1–31 years)] treated with aPCC [50 U kg−1 every 2 days or 3 days week−1
(n = 5)] or rFVIIa [90–100 μg kg−1 daily (n = 5)] for a median duration of 12 months (range 6–24 months) were identified for analysis. The aim of prophylaxis was to prevent or reduce bleeding complications and slow or prevent joint damage. Patients who were under consideration for ITI received rFVIIa. Pifithrin �� In eight of 10 EPZ-6438 patients (four out of five for both treatment groups), a reduction in bleeding episodes was observed during prophylaxis compared with preprophylaxis [median bleeding episodes per patient was 8.5 (range 3–19) pre-prophylaxis and 3 (0–10) during prophylaxis] (see Table 2). In terms of adverse events, no thromboembolic complications were detected in any patient, but three patients (one aPCC-treated
and two administered rFVIIa) developed CVAD infections. Two patients in the aPCC group also showed an increase in their inhibitor titre after beginning prophylaxis, whereas none of the rFVIIa-treated patients developed anamnesis. The investigators highlight that the aim of prophylaxis in the patients treated with aPCC was to reduce or prevent bleeding complications where ITI had failed or in whom ITI was not considered. Moreover, the individuals (three children and two adults) in the aPCC group were much older than the rFVIIa group, and three aPCC-treated patients had already developed target joints. In contrast, the aim of prophylaxis in the rFVIIa-treated group was to prevent or reduce bleeding complications in patients who were candidates for ITI. In this group, none of the patients had experienced more than one previous haemarthrosis and thus prophylaxis in these patients was considered to be primary prophylaxis.
Irrespective of the different ages and frequency of prior bleeding episodes in the two treatment groups, the investigators concluded that both aPCC and rFVIIa were similar in terms of efficacy and safety in decreasing the frequency of bleeding episodes. The investigators, however, did express concern that triclocarban aPCC can induce an anamnestic response in some patients, which could be an issue while awaiting a decline in inhibitor titres before initiating ITI. Therefore, rFVIIa would be the preferred option for prophylaxis in these usually young patients (while also enabling patients to begin ITI with a low number of haemarthrosis) . Two very different products are potentially available for prophylaxis in haemophilic patients who have developed inhibitors –aPCC and rFVIIa – each with their own proposed advantages and disadvantages (see Table 3) (Carcao, MD.