A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management

L A Valentino, V Mamonov, A Hellmann, D V Quon, A Chybicka, P Schroth, L Patrone, W-Y Wong, Prophylaxis Study Group, P W Collins, G Dolan, I Pabinger, L Nemes, A Nagy, Z Boda, R Jager, K Vezendi, A S Karafoulidou, O Katsarou, M Benedik Dolnicar, M Morfini, E Santgostino, M Penka, P Salaj, V Komrska, E Exster, M Reding, K Saxena, C Walsh, A Thompson, A Shapiro, M Recht, M Jacek Matysiak, A Skotnicki, A Dmoszynska, L Aledort, B Ewenstein, A Retzios, N Guzmán-Becerra, A Schneider, S Ott, C Thomasser, J Dyck-Jones, J Desmond, K Benamara, L A Valentino, V Mamonov, A Hellmann, D V Quon, A Chybicka, P Schroth, L Patrone, W-Y Wong, Prophylaxis Study Group, P W Collins, G Dolan, I Pabinger, L Nemes, A Nagy, Z Boda, R Jager, K Vezendi, A S Karafoulidou, O Katsarou, M Benedik Dolnicar, M Morfini, E Santgostino, M Penka, P Salaj, V Komrska, E Exster, M Reding, K Saxena, C Walsh, A Thompson, A Shapiro, M Recht, M Jacek Matysiak, A Skotnicki, A Dmoszynska, L Aledort, B Ewenstein, A Retzios, N Guzmán-Becerra, A Schneider, S Ott, C Thomasser, J Dyck-Jones, J Desmond, K Benamara

Abstract

Background: Prophylaxis with factor (F)VIII is considered the optimal treatment for managing hemophilia A patients without inhibitors.

Objectives: To compare the efficacy of two prophylaxis regimens (primary outcome) and of on-demand and prophylaxis treatments (secondary outcome), and to continue the evaluation of immunogenicity and overall safety of the ADVATE Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (rAHF-PFM).

Patients/methods: Previously on-demand-treated patients aged 7-59 years (n = 66) with FVIII levels ≤ 2% received 6 months of on-demand treatment and then were randomized to 12 months of either standard (20-40 IU kg(-1) every other day) or pharmacokinetic (PK)-tailored (20-80 IU kg(-1) every third day) prophylaxis, both regimens intended to maintain FVIII trough levels at or above 1%. Efficacy was evaluated in terms of annualized bleeding rates (ABRs). As subjects were first treated on-demand and then on prophylaxis, statistical comparisons between these treatments were paired.

Results: Twenty-two (33.3%) subjects on prophylaxis experienced no bleeding episodes, whereas none treated on-demand were free from an episode of bleeding. ABRs for the two prophylaxis regimens were comparable, whereas differences between on-demand and either prophylaxis were statistically significant (P < 0.0001): median (interquartile range [IQR]) ABRs were 43.9 (21.9), 1.0 (3.5), 2.0 (6.9) and 1.1 (4.9) during on-demand treatment, standard, PK-tailored and any prophylaxis, respectively. There were no differences in FVIII consumption or adverse event rates between prophylaxis regimens. No subject developed FVIII inhibitors.

Conclusions: The present study demonstrates comparable safety and effectiveness for two prophylaxis regimens and that prophylaxis significantly reduces bleeding compared with on-demand treatment. PK-tailored prophylaxis offers an alternative to standard prophylaxis for the prevention of bleeding.

Trial registration: ClinicalTrials.gov NCT00243386.

© 2011 International Society on Thrombosis and Haemostasis.

Figures

Fig 1
Fig 1
Study design.
Fig 2
Fig 2
Subject disposition flow diagram.
Fig 3
Fig 3
Comparison of annualized bleeding rates (ABRs). (A) Mean ABRs for each subject during treatment regimens (intention-to-treat [ITT] analysis set). (B) Median (interquartile range [IQR]) ABRs and percentage reductions during on-demand and any prophylaxis treatments. ND, not determined.

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Source: PubMed

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