(PL-WE-MED 1.3) Normalization - why, how, what?

Chronic non-curable diseases are those with the major burden for affected people, their families, society and healthcare system for several different reasons. Persons living with hemophilia (PwH), if not properly treated, may suffer from recurrent bleeds which can be life-threatening and/or can lead to permanent disability with pain, anxiety and depression. Their quality of life may be severely impacted as well as their ability to participate in academic, working and social life as their non-hemophilic peers. The widespread use of regular prophylaxis since early childhood has dramatically changed the course of the disease with relevant impact on all those aspects. The main goal of prophylaxis is to provide effective protection against bleeds and their potential consequences. Throughout the last decades prophylaxis has evolved thanks to the increasing knowledge about the importance of maintaining high level of protection over time to abolish as many bleeds as possible, including subclinical bleeds. Thanks to clinical experience and observation it was clear that the traditional dogma of maintaining factor trough levels at 1-3% was insufficient to protect joints from the development of chronic arthropathy and achieve the goal of zero bleeds. Higher levels of protection are needed and gradually the bar has been raised towards trough levels in the mild hemophilia range. Nevertheless joint damage develop also in people with non-severe hemophilia on the long-term if recurrent (subclinical) bleeds are not properly prevented. At variance with other chronic conditions as diabetes or arterial hypertension, for decades in the field of hemophilia the compromise of reaching the minimum protection level and not the full restoration of normal levels of clotting factor activity has been widely accepted. This was due mainly to treatment feasibility, affordability and sustainability with old generation replacement therapy. Thanks to the advent of extended half-life products including the ultra long-acting factor VIII molecule, efanesoctocog alfa, non-replacement therapies and gene therapies, the way towards the achievement and maintenance of levels of protection in the non-hemophilia range is becoming more and more realistic. This could be the way towards optimized wellbeing for all PwH.