Use of laquinimod for treating crohn's disease patients who failed first-line anti-tnf therapy

Abstract

This application provides for a method of treating a human patient afflicted with anti-TNFα refractory Crohn's disease, of treating a human patient afflicted with non-fibrostenotic Crohn's disease, and of treating a human patient whose Crohn's disease had not been surgically treated, the method comprising periodically administering to the patient an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the patient. This application also provides for a method of inducing or maintaining clinical remission in a human patient afflicted with Crohn's disease comprising periodically administering to the patient an amount of laquinimod effective to induce or maintain clinical remission in the patient, which amount of laquinimod is less than 0.5 mg/day.

What is claimed is: 
     
         1 . A method of treating a human patient afflicted with anti-TNFα refractory Crohn's disease, the method comprising periodically administering to the patient an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the patient. 
     
     
         2 . The method of  claim 1 , wherein the Crohn's disease is non-fibrostenotic Crohn's disease. 
     
     
         3 . The method of  claim 2 , wherein the Crohn's disease is inflammatory Crohn's disease. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the Crohn's disease is steroid refractory Crohn's disease. 
     
     
         5 . The method of any one of  claims 1 - 3 , wherein the patient has been administered oral steroids at baseline. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the patient's Crohn's disease had not been surgically treated. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the Crohn's disease is refractory to anti-TNFα treatment using infliximab, adalimimab, certolizumab or natalizumab. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the patient is naïve to anti-TNFα treatment. 
     
     
         9 . A method of treating a human patient afflicted with non-fibrostenotic Crohn's disease, the method comprising periodically administering to the patient an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the patient. 
     
     
         10 . The method of  claim 9 , wherein the non-fibrostenotic Crohn's disease is inflammatory Crohn's disease. 
     
     
         11 . The method of  claim 9 , wherein the patient has been administered oral steroids at baseline. 
     
     
         12 . The method of  claim 10  or  11 , wherein the Crohn's disease is steroid refractory Crohn's disease. 
     
     
         13 . The method of any one of  claims 10 - 12 , wherein the patient's Crohn's disease had not been surgically treated. 
     
     
         14 . A method of treating a human patient afflicted with Crohn's disease, the method comprising periodically administering to the patient an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the patient, wherein the patient's Crohn's disease had not been surgically treated. 
     
     
         15 . The method of  claim 14 , wherein the Crohn's disease is steroid refractory Crohn's disease. 
     
     
         16 . The method of claim any one of  claims 1 - 15 , wherein the amount of laquinimod is effective to reduce a symptom of Crohn's disease in the subject, induce clinical response, induce or maintain clinical remission, inhibit disease progression, or inhibit a disease complication in the subject. 
     
     
         17 . The method of  claim 16 , wherein the amount of laquinimod is effective to induce clinical remission in the patient. 
     
     
         18 . The method of  claim 16 , wherein the amount of laquinimod is effective to maintain clinical remission in the patient. 
     
     
         19 . The method of  claim 16 , wherein the amount of laquinimod is effective to induce and maintain clinical remission in the patient. 
     
     
         20 . The method of claim any one of  claims 1 - 19 , wherein the pharmaceutically acceptable salt of laquinimod is laquinimod sodium. 
     
     
         21 . The method of claim any one of  claims 1 - 20 , wherein the periodic administration is oral. 
     
     
         22 . The method of claim any one of  claims 1 - 21 , wherein the amount is administered by a unit dose of 0.25 mg of laquinimod. 
     
     
         23 . The method of claim any one of  claims 1 - 21 , wherein the amount is administered by a unit dose of 0.5 mg of laquinimod. 
     
     
         24 . The method of claim any one of  claims 1 - 23 , wherein the periodic administration is daily administration. 
     
     
         25 . The method of  claim 24 , wherein the amount of laquinimod is 0.1-1.0 mg/day. 
     
     
         26 . The method of  claim 24  wherein the amount of laquinimod is 0.1-0.75 mg/day. 
     
     
         27 . The method of  claim 24 , wherein the amount of laquinimod is 0.3-0.7 mg/day. 
     
     
         28 . The method of  claim 24 , wherein the amount of laquinimod is 0.25 mg/day. 
     
     
         29 . The method of  claim 24 , wherein the amount of laquinimod is 0.5 mg/day. 
     
     
         30 . The method of  claim 24 , wherein the amount of laquinimod is 1.0 mg/day. 
     
     
         31 . The method of any one of  claims 1 - 30 , wherein the laquinimod is administered as adjunct therapy with an other Crohn's disease treatment. 
     
     
         32 . Use of laquinimod for treating a patient afflicted with anti-TNFα refractory Crohn's disease. 
     
     
         33 . A pharmaceutical composition comprising laquinimod for use in treating a patient afflicted with anti-TNFα refractory Crohn's disease. 
     
     
         34 . Use of laquinimod for treating a patient afflicted with non-fibrostenotic Crohn's disease. 
     
     
         35 . A pharmaceutical composition comprising laquinimod for use in treating a patient afflicted with non-fibrostenotic Crohn's disease. 
     
     
         36 . Use of laquinimod for treating a patient afflicted with Crohn's disease, wherein the Crohn's disease had not been surgically treated. 
     
     
         37 . A pharmaceutical composition comprising laquinimod for use in treating a patient afflicted Crohn's disease, wherein the Crohn's disease had not been surgically treated. 
     
     
         38 . A method of inducing or maintaining clinical remission in a human patient afflicted with Crohn's disease comprising periodically administering to the patient an amount of laquinimod effective to induce or maintain clinical remission in the patient, which amount of laquinimod is less than 0.5 mg/day. 
     
     
         39 . The method of  claim 38 , wherein the amount of laquinimod is effective to induce clinical remission in the patient. 
     
     
         40 . The method of  claim 38 , wherein the amount of laquinimod is effective to maintain clinical remission in the patient. 
     
     
         41 . The method of  claim 38 , wherein the amount of laquinimod is effective to induce and maintain clinical remission in the patient. 
     
     
         42 . The method of any one of  claim 38 - 41 , wherein the amount of laquinimod 0.1-0.45 mg/day. 
     
     
         43 . The method of  claim 42 , wherein the amount of laquinimod is 0.25 mg/day. 
     
     
         44 . Use of a daily dose of less than 0.5 mg/day laquinimod for inducing or maintaining clinical remission in a human patient afflicted with Crohn's disease. 
     
     
         45 . A pharmaceutical composition comprising a unit dose of less than 0.5 mg laquinimod for inducing or maintaining clinical remission in a human patient afflicted with Crohn's disease.