Enzyme therapy of XXXX : clinical and biochemical changes during production of and tolerization for neutralizing antibodies.

@entity1 @entity66 @entity786 @entity15675 @entity1120
The clinical impact of neutralizing antibodies directed against the therapeutic enzyme was investigated in @entity1 with @entity1120 . Two @entity1 with @entity1120 were followed for their clinical progression during antibody development and clinical changes during tolerization. @entity1 1 developed neutralizing antibodies to @entity15675 (GCase) at the 10th month of enzyme therapy. Tolerization was achieved within a 42-month period with a short course of @entity786 and then higher dose enzyme (60 IU/kg/week) alone. @entity1 1 continues to improve up to 100 months of enzyme therapy despite the presence of low level in vitro neutralizing antibodies. Patient 2 developed neutralizing antibodies to GCase at the 29th month of enzyme therapy that correlated with clinical deterioration. Clinical stabilization has been observed with increased enzyme therapy (60 IU/kg/week) even in the presence of the neutralizing antibodies. Patient 2 is the first to develop neutralizing antibodies after 12 months of enzyme therapy. Plasma chitotriosidase activities were not well correlated with the clinical course in either @entity1 . The presence of neutralizing antibodies should be suspected in @entity1120 @entity1 on enzyme therapy who experience diminished response or deterioration. The persistence of minimal amounts of in vitro neutralizing antibodies does not interfere with the therapeutic effectiveness. Chitotriosidase is not a sensitive marker for the severity of @entity66 progression.
