The flexibility of the foundation system significantly affects the seismic and operational performance of Integral Abutment Bridges (IAB). The so-called pile isolation system can lead to higher flexibility in pile foundations. It consists in backfilling the pile hole with high-damping materials up to a certain depth from the surface level. This paper investigates the effectiveness of the pile isolation system by carrying out a multivariate sensitivity analysis of the seismic demand of a IAB structural archetype. The IAB archetype is modelled as a Winkler beam with a piece-wise definition of the subgrade stiffness and the equivalent viscous damping, simulating the responses of the soil and the high-damping particles. The multivariate sensitivity analysis of the seismic demand in terms of total shear force at the pile's head proves that the diameter and the earthquake scenario are the most sensitive parameters, compared to other geometrical characteristics of the pile, dynamics of the superstructure, and mechanical properties of the soil. Therefore, the paper proposes a probabilistic formulation for predicting the reduction of the seismic demand related to the pile isolation system. An extensive set of nonlinear dynamic analyses validates the proposed formulation for possible practical use in bridge engineering.