Figure 2.

Potential detrimental effects of ADAs against biologicals

(A) ADAs against biologicals can impair effectiveness of treatment by directly neutralizing the drug, rendering it incapable to perform its function. Neutralizing antibodies work immediately and are most strongly linked to reduced treatment efficacy. (B) Non-neutralizing antibodies can impact the pharmacokinetic profile of a drug by increasing clearance from the circulation, though its effect on treatment efficacy is more variable. It is presumed that with increased circulatory half-life, the relative importance of these non-neutralizing ADAs increases. (C) In addition to the effect on treatment efficacy, ADAs can induce infusion reactions. Classical infusion reactions are common in male patients with classical FD and are characterized by a sudden onset of fever, cold chills, nausea, and general malaise, which recover quickly after stopping the infusion. (D) Finally, it has been described for biologicals other than ERT for Fabry disease that ADA-drug aggregates can accumulate in the vascular wall or in the kidney, causing vasculitis, thrombosis, and renal failure. Although rare, the occurrence of this complication should be monitored for every new biological.