Impact of immunosuppressive therapy on therapy‐neutralizing antibodies in transplanted patients with Fabry disease. (26th July 2017) - Lenders, M.
Abstract: Background: Inhibitory antibodies towards enzyme replacement therapy (ERT) are associated with disease progression and poor outcome in affected male patients with lysosomal disorders such as Fabry disease (FD). However, little is known about the impact of immunosuppressive therapy on ERT inhibition in these patients with FD. Methods: In this retrospective study, we investigated the effect of long‐term immunosuppression on ERT inhibition in male patients with FD ( n = 26) receiving immunosuppressive therapy due to kidney ( n = 24) or heart ( n = 2) transplantation. Results: No ERT‐naïve transplanted patient ( n = 8) developed antibodies within follow‐up (80 ±72 months) after ERT initiation. Seven (26.9%) patients were tested ERT inhibition positive prior to transplantation. No de novo ERT inhibition was observed after transplantation ( n = 18). In patients treated with high dosages of immunosuppressive medication such as prednisolone, tacrolimus and mycophenolate‐mofetil/mycophenolate acid, ERT inhibition decreased after transplantation ( n = 12; P = 0.0160). Tapering of immunosuppression (especially prednisolone) seemed to re‐increase ERT inhibition ( n = 4, median [range]: 16.6 [6.9; 36.9] %; P = 0.0972) over time. One ERT inhibition‐positive patient required interventions with steroid therapy and increased doses of tacrolimus, which also lowered ERT inhibition. Conclusion: We conclude that the immunosuppressive maintenance therapy after transplantations seems to be sufficient to prevent de novo ERT inhibition in ERT‐naïve patients. Intensified high dosages of immunosuppressive drugs are associated with decreased antibody titres and decreased ERT inhibition in affected patients, but did not result in long‐term protection. Future studies are needed to establish ERT inhibition‐specific immunosuppressive protocols with long‐term modulating properties to warrant an improved disease course in ERT inhibition‐positive males.