The availability of emicizumab (Hemlibra) means that prophylaxis can now be offered for previously untreated infants with severe haemophilia A (SHA) without inhibitors, according to haematologists in Queensland.
The monoclonal inhibitor product has been licensed for use in patients of all ages with SHA, but haematologists may have to make important treatment decisions for infants despite a dearth of evidence of its use in the younger age groups, according to an article by clinicians from the Queensland Haemophilia Centre, Royal Brisbane and Women’s Hospital.
Writing in the journal Haemophilia, Dr Jane Mason and Dr Guy Young say emicizumab’s subcutaneous administration and long half-life make it an attractive additional option for prophylaxis in infants with SHA. And until data from trials in infants become available, they have shared their experience of several real world cases where they have used emicizumab in different treatment scenarios, to help inform practice.
“These include emicizumab prophylaxis following initial treatment of an intracranial haemorrhage [ICH], early emicizumab to reduce the risk of ICH, emicizumab in lieu of standard primary prophylaxis with FVIII concentrates, or deferring emicizumab until a target number of FVIII concentrate exposure days is achieved,” they wrote.
In the first example, emicizumab was given to a 7-day old infant with SHA who had experienced a bilateral grade 2 intraventricular haemorrhage (IVH). The infant had been treated initially with FVIII but it was very difficult to maintain reliable peripheral intravenous access. After discussion with the parents, emic was started in an attempt to avoid the need for a central venous line, and FVIII infusion was ceased when the fourth attempt at a IV cannula was lost. Repeat cranial ultrasound at day 10 showed complete resolution of the IVH.
In a second and more challenging case, emicizumab was started in a five week old infant with SHA as prophylaxis, after parents insisted every possible measure must be taken to prevent ICH. The child subsequently had no bleeding events up to the age of 22 months.
In a similar scenario, some other parents opted against emicizumab for their infant initially, after discussing the lack of data for its use, but elected to start prophylaxis when their child reached 15 months of age, primarily as a means to avoid venipuncture or a CVAD.
And in a fourth case the parents of an infant with SHA agreed to initiate prophylaxis using an extended half-life FVIII concentrate every three days, but switched to emicizumab after 44 exposure days when venipuncture access became more challenging.
The authors of the article said that while there were still no phase 3 studies performed with emicizumab in previously untreated infant patients, emerging observational data and retrospective studies offered some reassurance that it appeared to be highly effective and safe in young children with and without inhibitors.
Advantages included the subcutaneous mode of administration to avoid venipuncture, they said, as well as allowing initiation in the early newborn period to treat or prevent ICH and also to prevent joint bleeding at an earlier age than currently feasible.
“The availability of emicizumab has dramatically altered the treatment landscape for patients of all ages with SHA. While a strong evidence base exists for older children and adolescents, there are limited [data] regarding the use of emicizumab in infants. Nonetheless there are undeniably potential advantages that emicizumab offers over FVIII concentrates in this younger patient population,” they concluded.