Hemophilia Prophylaxis No Longer Just for Children without Inhibitors - Increasing Use of Prophylaxis in Other Groups (children with inhibitors and adults with and without inhibitors)
Authors: Carcao Manuel , Avila Maria L. , Blanchette Victor S. , Santagostino Elena , Escuriola-Ettingshausen Carmen , Leissinger Cindy A. , Lambert Thierry , Aledort Louis M. 
Published: October 2019

Background: Long-term prophylaxis is standard of care in children with severe hemophilia A (SHA) and B (SHB) without inhibitors. Studies have shown benefit from long-term prophylaxis in adults with SH and in both adults and children with SH and inhibitors. Yet there is little data on the prevalence of prophylaxis in these groups.

Aim/Methods: To understand the current use of long-term prophylaxis in these groups of patients in countries capable of underwriting the high cost of prophylaxis we surveyed (2013) hemophilia treatment centers (HTCs) in countries where long-term prophylaxis in children is routinely used.

Results: 134 HTC from 14 countries in North America, Australasia, and Western Europe reported on 4,763 adults with SH (4,011 SHA; 752 SHB) and on 751 children and adults with inhibitors. Prophylaxis use in these groups is shown in table 1:

Table 1. Prophylaxis use in adults with SH (without inhibitors). Adults without inhibitors Children and adults with inhibitors HA HB In ITI setting In non-ITI setting % on Prophylaxis 59 49 29 28 Most common regimen EOD 2 d/wk FEIBA EOD or 3 d/wk FEIBA EOD or 3 d/wk

EOD, every other day

Adults without inhibitors: A higher proportion of SHA (59%) vs SHB adults (49%) were on prophylaxis (Χ2 p<.001). This was particularly true in the age group of 18-30 y [74% (SHA) vs 60% (SHB)]. For SHA the use of prophylaxis was progressively less in older age groups: 31-40 y (55%), 41-50 y (47%), 51-70 y (39%) and >70 y (29%). There was little drop in the proportion of SHB adults on prophylaxis with increasing age. 67% of SHA adults on prophylaxis were receiving ≥3 infusions/wk while 80% of SHB adults on prophylaxis were receiving ≥2 infusions/wk. Once/wk prophylaxis was reported in 3% of SHA and by 19% of SHB patients on prophylaxis. Daily prophylaxis was rarely reported in both groups.

Children and adults with inhibitors: Data was available on 407 children and 344 adults with SH and inhibitors. Table 2 shows the proportion of children and adults on/not on Immune tolerance induction (ITI) and on/not on bypassing agent prophylaxis (BA-P). Most children (78%) were on either ITI (with or without BA-P) or on BA-P alone and as such were having some bleed protection. In contrast only 28% of adults were on either ITI (with or without BA-P) or on BA-P and as such most adults with inhibitors are not on any bleed protection.

Table 2. Use of ITI and of BA-P in children and adults with SH (+ inhibitors). 403 children 344 adults On ITI. Not on BA-P 43% 8% On ITI. On BA-P 17% 4% Not on ITI. Not on BA-P 23% 71% Not on ITI. On BA-P 18% 16%

In total, 185 patients had received FEIBA prophylaxis while 70 had received rFVIIa prophylaxis. FEIBA prophylaxis was particularly more common (vs. rFVIIa prophylaxis) in the non-ITI setting [FEIBA (n=107 pts) vs rFVIIa (n=33 pts)]. The most common prophylactic FEIBA regimen was EOD or 3/wk while the most common rFVIIa prophylaxis regimen was daily.

Conclusions: This survey captured data on 4,763 adults with SHA/SHB and on 751 adults and children with SH and inhibitors. This is the largest survey of prophylaxis in these 2 groups of patients. Given the benefits of prophylaxis in children it is reassuring to observe that prophylaxis in adults (without inhibitors) is more prevalent than previously reported. Use of BA-P in patients with inhibitors still however lags far behind the use of prophylaxis in non-inhibitor patients - particularly in adults. FEIBA is more commonly used for prophylaxis than rFVIIa. Our survey did not capture longterm patient outcome data; this needs evaluation.

Note: This abstract includes data presented as separate abstracts at the ISTH 2015 meeting. The data has been combined and analyzed in this abstract to show the increasing use of prophylaxis outside of children without inhibitors.

Disclosures

Blanchette: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Data Safety Monitoring Board; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Board, Research Funding. Santagostino:CSL Behring: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Biogen/Sobi: Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Kedrion: Speakers Bureau; Biotest: Speakers Bureau; Octapharma: Speakers Bureau; Roche: Speakers Bureau. Leissinger:Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Aledort:Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: DSMB Participation; Kedrion BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.