METHODS OF TREATING SYSTEMIC LUPUS ERYTHEMATOSUS USING BTK INHIBITORS

1 . A method for treating systemic lupus erythematosus, the method comprising administering to a subject a therapeutically effective amount of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyrimidine-3-carboxamide (Compound 1) or a pharmaceutically acceptable salt thereof.

2 . A method for treating lupus nephritis, the method comprising administering to a subject a therapeutically effective amount of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyrimidine-3-carboxamide (Compound 1) or a pharmaceutically acceptable salt thereof,

3 . The method of claim 1 , wherein the lupus nephritis is active proliferative lupus nephritis.

4 . The method of any one of claims 1 to 3 , wherein the subject is a patient, who meet one of the inclusion criteria consisting of the following, Clinical diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics 2012 criteria;

a) ISN/RPS Class III/IV lupus nephritis [Type III (A), III (A+C), IV (A), and IV (A+C)], with or without Class V, as confirmed by a renal biopsy;

b) Positive antinuclear antibodies, positive anti-dsDNA autoantibody, and/or positive anti-Smith autoantibody at screening; and,

c) Having 24-hour urine protein excretion >1.0 g at screening.

5 . The method of any one claims 1 to 3 , wherein Compound 1 is administrated at a dose which achieve sustained BTK occupancy >90% in PBMCs and >70% in spleens.

6 . The method of any one of claims 1 to 3 , wherein Compound 1 is administered at a dose of 10 mg-640 mg per day, preferably 10 mg-320 mg per day, more preferably 40-320 mg per day, most preferably 80-320 mg per day.

7 . The method of any one of claims 1 to 3 , wherein Compound 1 is administered at a dose of 40 mg-160 mg per day, preferably 80 mg-160 mg per day.

8 . The method of any one of claims 1 to 3 , wherein Compound 1 is orally administrated at a dose of 5 mg-320 mg twice daily (BID), preferably 5 mg-160 mg BID, more preferably 20 mg-160 mg BID, most preferably 40 mg-160 mg BID.

9 . The method of any one of claims 1 to 3 , wherein Compound 1 is orally administrated at a dose of 10 mg-640 mg once daily (QD), preferably 10 mg-320 mg QD, more preferably 40 mg-320 mg QD, most preferably 40 mg-160 mg QD.

10 . The method of any one of claims 1-8 , wherein the subject shows an positive level of autoantibody including anti-dsDNA IgG in serum.

11 . The method of claim 1 , wherein systemic lupus erythematosus includes lupus nephritis, neuropsychiatric lupus, lupus pneumonia, lupus myocarditis and lupus hepatitis.

12 . The method of claim 2 , wherein lupus nephritis is any one of the following lupus nephritis:

Minimal mesangial lupus nephritis;

Mesangial proliferative lupus nephritis;

Focal lupus nephritis;

Diffuse segmental (IV-S) or global (IV-G) lupus nephritis;

Membranous lupus nephritis; or

Advanced sclerosing lupus nephritis.