Presumably, inhibitors will form in some patients upon exposure t

Presumably, inhibitors will form in some patients upon exposure to the deficient factor independent of

any co-existent pro-inflammatory signals, whereas in others these signals will be significant modifiers. In some subjects, only minor inflammatory signals will be needed, whereas in others a more pronounced pro-inflammatory state will be required. A third group of patients will, presumably, never develop inhibitors despite how, when, and with what replacement product they are treated, as long as the agent itself is not immunogenic. One approach is to avoid the deficient factor at start of treatment, since without this exposure antibodies will not be formed. This approach has been tested, but so far without success. Rivard and colleagues evaluated the use of recombinant Ivacaftor factor VIIa to postpone exposure to FVIII until after the age of 2 years, Autophagy pathway inhibitors but succeeded in only 3 of 11 children treated a mean

of 5.5 months (median 4, range 0–12) [28]. Therefore, to use this approach other treatment options than currently available will probably be needed. Another emerging method is the use of low dose prophylaxis in the absence of any tissue damage. This includes very small doses, such as 5–10 IU/kg body weight, as these doses may not only protect against bleeding in a cost-effective manner, but also sensitize the immune system and thereby minimize the risk for inhibitors in the event of a major trauma and bleed. Although, in the context of inhibitors, prophylaxis will be neither required nor of benefit for all, its use should continue to be the state-of-the-art treatment for all patients. In summary, there has been major progress during the last decade in the understanding of how and why patients develop inhibitory antibodies to the deficient factor. However,

a substantial number of issues remain to be resolved including how to better identify patients at high risk before start of treatment using a genetic risk score. New treatment options in the pipeline may emerge in the near future and be offered to patients who are at high risk. Gene therapy may provide another attractive approach. However, from logistic and health-economic selleck compound perspectives, this potentially curative option will likely not be widely available. New – less expensive – therapeutic options need to be continually evaluated and the resources available must be used in the most optimal way. On the basis of current knowledge, this includes low dose prophylaxis initiated prior to the onset of bleeds. Studies to evaluate doses even lower than those currently utilized should be performed in countries in which this treatment modality is not currently available. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “

Comments are closed.