JAK1 pathway inhibitors for the treatment of chronic lung allograft dysfunction

A method of reducing the risk of bronchiolitis obliterans syndrome in a subject, said method comprising administering to the subject 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, or a pharmaceutically acceptable salt thereof.

A method of reducing the risk of lung re-transplantation in a subject, said method comprising administering to the subject 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, or a pharmaceutically acceptable salt thereof.

A method of reducing the risk of hospitalization in a subject, said method comprising administering to said subject an effective amount of 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-R1S)-2,2,2-trifluoro-1-methylethyljbenzamide, or a pharmaceutically acceptable salt thereof, wherein said subject is (a) diagnosed with bronchiolitis obliterans syndrome;

• (b) has had a lung transplantation within 1 to 5 years prior to administering the, 4 [3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, or a pharmaceutically acceptable salt thereof, and (c) does not have a decrease in FEVs attributable to a cause other than bronchiolitis obliterans syndrome.

A method of treating bronchiolitis obliterans syndrome in a subject, said method comprising administering to the subject a pharmaceutically acceptable salt of 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide.