Treatment of lupus nephritis using laquinimod

Abstract

This invention provides a method of treating a subject afflicted with active lupus nephritis comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the subject. This invention also provides laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with active lupus nephritis. This invention further provides a pharmaceutical composition comprising an amount of laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with active lupus nephritis.

What is claimed is: 
     
         1 . A method of treating a subject afflicted with active lupus nephritis comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the subject. 
     
     
         2 . The method of  claim 1 , wherein the pharmaceutically acceptable salt of laquinimod is laquinimod sodium. 
     
     
         3 . The method of  claim 1  or  2 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof is effected orally. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the amount of laquinimod administered is 0.5-1.0 mg/day. 
     
     
         5 . The method of  claim 4 , wherein the amount of laquinimod administered is 0.5 mg/day. 
     
     
         6 . The method of  claim 4 , wherein the amount of laquinimod administered is 1.0 mg/day. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce a clinical symptom of active lupus nephritis in the subject. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof is effective to elicit at least a partial response by the subject by week 24. 
     
     
         9 . The method of  claim 8 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof is effective to elicit a complete response by the subject by week 24. 
     
     
         10 . The method of any one of  claims 1 - 9 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof reduces proteinuria in the subject. 
     
     
         11 . The method of  claim 10 , wherein proteinuria reduction is measured by 24 hour urine protein, 24 hour protein to creatinine ratio, spot protein to creatinine ratio, 24 hour urine albumin, 24 hour albumin to creatinine ratio, spot albumin to creatinine ratio, or by a urinary dipstick. 
     
     
         12 . The method of any one of  claims 1 - 11 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof reduces the subject's protein to creatinine ratio. 
     
     
         13 . The method of  claim 12 , wherein the subject's protein to creatinine ratio is reduced by at least 50% as compared to baseline. 
     
     
         14 . The method of  claim 12  or  13 , wherein the subject's protein to creatinine ratio is reduced to no more than 0.3. 
     
     
         15 . The method of  claim 12 , wherein the subject's protein to creatinine ratio is less than 3 and wherein the subject's serum creatinine level is either less than 1.3 mg/dL or did not increase by more than 10% relative to baseline. 
     
     
         16 . The method of  claim 12 , wherein the subject's protein to creatinine ratio is less than 0.5 and wherein the subject's serum creatinine level is either less than 1.3 mg/dL or decreased by at least 25% relative to baseline. 
     
     
         17 . The method of anyone of  claims 1 - 16 , wherein the period administration of laquinimod or pharmaceutically acceptable salt thereof eliminates urinary sediments. 
     
     
         18 . The method of any one of  claims 1 - 17 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof improves the subject's BILAG index 
     
     
         19 . The method of any one of  claims 1 - 18 , wherein the method further comprises administration of mycophenolate mofetil. 
     
     
         20 . The method of  claim 19 , wherein the periodic administration of mycophenolate mofetil is effected orally. 
     
     
         21 . The method of  claim 19  or  20 , wherein the amount of mycophenolate mofetil administered is 1-3 g/day. 
     
     
         22 . The method of  claim 21 , wherein the amount of mycophenolate mofetil administered is 2 g/day. 
     
     
         23 . The method of any one of  claims 1 - 22 , further comprising administering to the subject an amount of a steroid. 
     
     
         24 . The method of  claim 23 , wherein the administration of the steroid is periodic administration. 
     
     
         25 . The method of  claim 23  or  24 , wherein the administration of steroids is effected orally and/or intravenously. 
     
     
         26 . The method of any one of  claims 23 - 25 , wherein the amount of steroid administered is 500 mg/day methylprednisolone. 
     
     
         27 . The method of any one of  claims 23 - 25 , wherein the amount of steroid administered is 40 mg/day prednisolone and/or prednisone. 
     
     
         28 . The method of any one of  claims 1 - 27 , further comprising administration of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), antimalarials, statins, cyclophosphamide, azathioprine, 6-mercaptopurine, abatacept, rituximab, belimumab, cyclosporine or other calcineurin inhibitors. 
     
     
         29 . The method of any one of  claims 1 - 28 , wherein the periodic administration continues for at least 24 weeks. 
     
     
         30 . The method of any one of  claims 19 - 29 , wherein the amount of laquinimod or pharmaceutically acceptable salt thereof and the amount of mycophenolate mofetil together is effective to reduce a clinical symptom of active lupus nephritis in the subject. 
     
     
         31 . The method of any one of  claims 19 - 30 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil is effective to elicit at least a partial response by the subject by week 24. 
     
     
         32 . The method of  claim 31 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil is effective to elicit a complete response by the subject by week 24. 
     
     
         33 . The method of any one of  claims 19 - 32 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil reduces proteinuria in the subject. 
     
     
         34 . The method of  claim 33 , wherein proteinuria reduction is measured by 24 hour urine protein, 24 hour protein to creatinine ratio, spot protein to creatinine ratio, 24 hour urine albumin, 24 hour albumin to creatinine ratio, spot albumin to creatinine ratio, or by a urinary dipstick. 
     
     
         35 . The method of any one of  claims 19 - 34 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil reduces the subject's protein to creatinine ratio. 
     
     
         36 . The method of  claim 35 , wherein the subject's protein to creatinine ratio is reduced by at least 50% as compared to baseline. 
     
     
         37 . The method of  claim 35  or  36 , wherein the subject's protein to creatinine ratio is reduced to no more than 0.3. 
     
     
         38 . The method of  claim 35 , wherein the subject's protein to creatinine ratio is less than 3 and wherein the subject's serum creatinine level is either less than 1.3 mg/dL or did not increase by more than 10% relative to baseline. 
     
     
         39 . The method of  claim 35 , wherein the subject's protein to creatinine ratio is less than 0.5 and wherein the subject's serum creatinine level is either less than 1.3 mg/dL or decreased by at least 25% relative to baseline. 
     
     
         40 . The method of anyone of  claims 19 - 39 , wherein the period administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil eliminates urinary sediments. 
     
     
         41 . The method of any one of  claims 19 - 40 , wherein the periodic administration of laquinimod or pharmaceutically acceptable salt thereof and mycophenolate mofetil improves the subject's BILAG index. 
     
     
         42 . The method of any one of  claims 19 - 41 , wherein each of the amount of laquinimod or pharmaceutically acceptable salt when taken alone, and the amount of mycophenolate mofetil when taken alone is effective to treat the subject. 
     
     
         43 . The method of any one of  claims 19 - 41 , wherein either the amount of laquinimod or pharmaceutically acceptable salt when taken alone, the amount of mycophenolate mofetil when taken alone, or each such amount when taken alone is not effective to treat the subject. 
     
     
         44 . The method of any one of  claims 19 - 43 , wherein the subject is receiving mycophenolate mofetil therapy prior to initiating laquinimod therapy. 
     
     
         45 . The method of any one of  claims 1 - 44 , wherein the subject is human. 
     
     
         46 . Laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with active lupus nephritis. 
     
     
         47 . Laquinimod or pharmaceutically acceptable salt thereof for use in combination with mycophenolate mofetil for treating a subject afflicted with active lupus nephritis. 
     
     
         48 . A pharmaceutical composition comprising an amount of laquinimod or pharmaceutically acceptable salt thereof for use in treating a subject afflicted with active lupus nephritis. 
     
     
         49 . A pharmaceutical composition comprising an amount of laquinimod or pharmaceutically acceptable salt thereof and an amount of mycophenolate mofetil for use in treating a subject afflicted with active lupus nephritis.