Polypeptides are provided directed against IL-6R at specific dose ranges and dosing schedules that result in a prolonged effect on IL-6 mediated signaling. In particular, the invention provides pharmacologically active agents, compositions, methods and/or dosing schedules that have certain advantages compared to the agents, compositions, methods and/or dosing schedules that are currently used and/or known in the art, including the ability to dose less frequently or to administer lower doses to obtain equivalent effects in inhibiting IL-6 mediated signaling.