T.P.19: Effects of antibody formation during enzyme replacement therapy in 73 adult patients with Pompe disease

Abstract

High sustained antibody titers against enzyme replacement therapy (ERT) with alglucosidase alfa adversely affect clinical outcome in classic-infantile Pompe disease. The long-term effects of antibody formation on therapeutic efficacy in non-classic Pompe disease are yet unknown. We studied whether the presence of anti-alglucosidase alfa antibodies has an impact on treatment outcome and occurrence of infusion-associated reactions (IARs) in a large cohort of adult patients. This prospective single-centre cohort study included 73 adult patients who were treated with 20 mg/kg alglucosidase alfa every other week and started to receive ERT at least 3 years ago. Antibody titers were measured at approximately 6, 12 and 36 months of ERT using ELISA and their effects on enzyme activity were measured in the medium and in cultured fibroblasts in vitro . Clinical parameters included muscle strength (MRC sumscore), pulmonary function (FVC in upright and supine positions), and IARs. 71 of the 73 (97%) patients developed antibodies against alglucosidase alfa. The mean titer peaked at 6 months to 1:1259 and thereafter declined to 1:270 at 36 months of treatment. Individual titers and titer courses varied, but in the majority (93%) of patients titers decreased or stabilized with continued ERT. Patients with high peak titers showed moderate to high levels of in vitro enzyme inhibition. An increased risk for IARs was found in patients with higher antibody peak titers as 7 (44%) of 16 patients with high titers (⩾1:31,250) experienced IARs, 5 (19%) of 27 patients with intermediate titers (1:1250 to p = 0.001). No relation was found with antibody titer and poorer clinical outcome for MRC sumscore and FVC in upright and supine positions after a 36 months treatment period. Antibody formation to alglucosidase alfa in non-classic Pompe patients increases the risk for infusion-associated reactions, but is not associated with unfavorable clinical outcome during 3 years of treatment.