Compositions and methods for treating granulomatosis with polyangiitis
The present specification disclose methods and uses for the treatment of a vasculitic syndrome. The disclosed methods comprise administering a composition comprising a Proteinase 3 (PR3) inhibitor to a patient in need thereof. Also disclosed are compositions comprising a PR3 inhibitor disclosed herein for use in the treatment of a vasculitic syndrome as well as use of a composition comprising a PR3 inhibitor disclosed herein in the treatment of a vasculitic syndrome. The present specification also discloses use of a composition comprising a PR3 inhibitor disclosed herein in the manufacture of a medicament for the treatment of a vasculitic syndrome.
1 . A method for treating Granulomatosis with Polyangiitis (GPA) in a patient in need thereof comprising administering a therapeutically effective amount of a Proteinase 3 (PR3) inhibitor to the patient, wherein administration inhibits a physiological function of PR3, thereby treating GPA, wherein the PR3 inhibitor is selected from elafin, Trappin-2, Eglin c, α-1 antichymotrypsin, and α-2 macroglobulin.
2 . The method according to claim 1 , wherein the PR3 inhibitor is administered weekly or bi-weekly.
3 . The method according to claim 1 , wherein the PR3 inhibitor is administered systemically.
4 . The method according to claim 1 , wherein the PR3 inhibitor is administered by inhalation, enterally or parenterally.
5 . The method according to claim 1 , wherein the PR3 inhibitor is administered intravenously, by inhalation, orally, intramuscularly, intraarterially, nasally, intracardiac, subcutaneously, or transmucosally.
6 . The method according to claim 1 , wherein the PR3 inhibitor is administered at one of the following doses: 1-1000 mg/kg, 1-500 mg/kg, 1-200 mg/kg, 1-100 mg/kg, 1-50 mg/kg, 10-500 mg/kg, 10-250 mg/kg, 10-200 mg/kg, 10-150 mg/kg, 10-100 mg/kg, 10-50 mg/kg, 50-1000 mg/kg, 50-500 mg/kg, 50-250 mg/kg, 50-200 mg/kg, 50-150 mg/kg, 50-100 mg/kg, 20-500 mg/kg, 20-250 mg/kg, 20-200 mg/kg, 20-150 mg/kg, 20-100 mg/kg, or 20-60 mg/kg.
7 . The method according to claim 6 , wherein the PR3 inhibitor is administered weekly at 50 to 500 mg/kg.
8 . The method according to claim 6 , wherein the PR3 inhibitor is administered weekly at 50 to 250 mg/kg.
9 . The method of claim 1 , wherein the administering comprises administering a loading dose and a maintenance dose of the PR3 inhibitor.
10 . The method of claim 9 , wherein the loading dose is administered weekly or bi-weekly.
11 . The method of claim 9 , wherein the loading dose is administered weekly at a dose of 50 to 150 mg/kg.
12 . The method of claim 9 , wherein the maintenance dose is administered weekly.
13 . The method of claim 9 , wherein the maintenance dose comprises 25% to 80% of the PR3 inhibitor of the loading dose.