PROLONGED INHIBITION OF INTERLEUKIN-6 MEDIATED SIGNALING

摘要

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.

主权项

1. A method for inhibiting IL-6 mediated signaling in a subject comprising administering to the subject a polypeptide that specifically binds IL-6R, wherein the amount of the polypeptide administered is effective:
to increase total sIL-6R levels in serum to at least 400 ng/ml and to maintain total sIL-6R levels in serum at at least 400 ng/ml; to increase total IL-6 levels in serum to at least 40 pg/ml and to maintain total IL-6 levels in serum at at least 40 pg/ml; to reduce CRP levels in serum below 10 mg/l and to maintain CRP levels in serum below 10 mg/l; to reduce CRP levels in serum by 50% or more compared to baseline (i.e. pre-treatment or normal) levels and to maintain CRP levels in serum at 50% or more reduction compared to baseline levels; to reduce ESR levels in serum by 30% or more compared to baseline (i.e. pre-treatment or normal) levels and to maintain ESR levels in serum at 30% or more reduction compared to baseline levels; to reduce fibrinogen levels in serum by 30% or more compared to baseline (i.e. pre-treatment or normal) levels and to maintain fibrinogen levels in serum at 30% or more reduction compared to baseline levels; and/or to reduce serum amyloid A levels by 30% or more compared to baseline (i.e. pre-treatment or normal) levels and to maintain serum amyloid A levels at 30% or more reduction compared to baseline levels;for at least 4 weeks after administration.