Treatment of ocular inflammatory diseases using laquinimod

Abstract

Disclosed is a method for treating an ocular inflammatory disease (OID), e.g., uveitis or conjunctivitis, comprising periodic administration of a therapeutically effective amount of laquinimod or a pharmaceutically acceptable salt thereof. Also provided is a pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof for use in treating a subject suffering from an OID, uveitis, bacterial conjunctivitis, viral conjunctivitis, an inflammation of the orbital tissue, the lacrimal apparatus, the eyelid, the cornea, the retina or the optic pathway. This application also provides a method for treating a subject suffering from an autoimmune disease-associated ocular inflammation comprising periodic ocular administration to the subject a therapeutically effective amount of laquinimod or a pharmaceutically acceptable salt, and an ocular pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof for use in treating an autoimmune disease-associated ocular inflammation.

What is claimed is: 
     
         1 . A method of treating a subject suffering from an ocular inflammatory disease, the method comprising periodic administration to the subject of a therapeutically effective amount of laquinimod or a pharmaceutically acceptable salt thereof effective to treat the subject. 
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount of laquinimod is effective to reduce a symptom of the ocular inflammatory disease in the subject, induce clinical response, induce or maintain clinical remission, inhibit disease progression, inhibit a disease complication, reduce intraocular inflammation or reduce retina tissue destruction in the subject. 
     
     
         3 . The method of  claim 1  or  2 , wherein the ocular inflammatory disease is uveitis, bacterial conjunctivitis, viral conjunctivitis, or an inflammation of the orbital tissue, the lacrimal apparatus, the eyelid, the cornea, the retina or the optic pathway. 
     
     
         4 . The method of  claim 3 , wherein the ocular inflammatory disease is conjunctivitis and the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce a symptom of conjunctivitis in the subject. 
     
     
         5 . The method of  claim 3 , wherein the ocular inflammatory disease is uveitis and the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce a symptom of uveitis in the subject. 
     
     
         6 . The method of  claim 5 , wherein the uveitis is anterior uveitis, intermediate uveitis, posterior uveitis, or diffuse uveitis. 
     
     
         7 . The method of  claim 3 , wherein the ocular inflammatory disease is an inflammation of the orbital tissue, the lacrimal apparatus, the eyelid, the cornea, the retina or the optic pathway and the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce a symptom of the inflammation in the subject. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the laquinimod or pharmaceutically acceptable salt thereof is administered in the form of a liquid or a gel. 
     
     
         9 . The method of  claim 8 , wherein the concentration of laquinimod or pharmaceutically acceptable salt thereof in the liquid or gel 5-100 mg/ml solution. 
     
     
         10 . The method of  claim 9 , wherein the concentration of laquinimod or pharmaceutically acceptable salt thereof is 10-15 mg/ml solution. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is 0.05-4.0 mg per administration. 
     
     
         12 . The method of  claim 11 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is 0.05-2.0 mg per administration. 
     
     
         13 . The method of  claim 12 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is about 0.1 mg per administration. 
     
     
         14 . The method of  claim 12 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is about 0.5 mg per administration. 
     
     
         15 . The method of  claim 1  or  2 , wherein the ocular inflammatory disease is allergic conjunctivitis or uveitis and wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is at least 0.2 mg/day. 
     
     
         16 . The method of  claim 15 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce a symptom of the allergic conjunctivitis or uveitis in the subject. 
     
     
         17 . The method of  claim 15  or  16 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to inhibit late ocular anaphylaxis in the subject 
     
     
         18 . The method of any one of  claims 15 - 17 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is effective to reduce eosinophil infiltration into the conjunctiva of the subject. 
     
     
         19 . The method of  claim 18 , wherein the eosinophil infiltration into the conjunctiva is measured by eosinophil density in the conjunctiva. 
     
     
         20 . The method of  claim 19 , wherein the eosinophil density is reduced by at least 40% as compared to a subject not administered laquinimod or pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 20 , wherein the eosinophil density is reduced by at least 60% as compared to a subject not administered laquinimod or pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of any one of  claims 15 - 21 , wherein the laquinimod or pharmaceutically acceptable salt thereof is administered in the form of a liquid or a gel. 
     
     
         23 . The method of  claim 22 , wherein the concentration of laquinimod or pharmaceutically acceptable salt thereof in the liquid or gel is 20-100 mg/ml solution. 
     
     
         24 . The method of  claim 23 , wherein the concentration of laquinimod or pharmaceutically acceptable salt thereof is 20-50 mg/ml solution. 
     
     
         25 . The method of any one of  claims 15 - 24 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is 0.2-4.0 mg per administration. 
     
     
         26 . The method of  claim 25 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is 0.2-2.0 mg per administration. 
     
     
         27 . The method of  claim 26 , wherein the therapeutically effective amount of laquinimod or pharmaceutically acceptable salt thereof is about 0.5 mg per administration. 
     
     
         28 . The method of any one of  claims 1 - 27 , wherein the periodic administration is once per day. 
     
     
         29 . The method of any one of  claims 1 - 28 , wherein the periodic administration is oral administration. 
     
     
         30 . The method of any one of  claims 1 - 29 , wherein the periodic administration is ocular administration. 
     
     
         31 . The method of any one of  claims 1 - 30 , wherein the pharmaceutically acceptable salt of laquinimod is laquinimod sodium. 
     
     
         32 . The method of any one of  claims 1 - 31 , wherein the subject is a human. 
     
     
         33 . A pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof for use in treating a subject suffering from an ocular inflammatory disease. 
     
     
         34 . A pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof for use in treating a subject suffering from uveitis, bacterial conjunctivitis, viral conjunctivitis, or an inflammation of the orbital tissue, the lacrimal apparatus, the eyelid, the cornea, the retina or the optic pathway. 
     
     
         35 . A pharmaceutical composition for use in treating a subject suffering from allergic conjunctivitis or uveitis comprising a unit dose of 10 μL of an aqueous pharmaceutical solution which contains in solution at least 0.2 mg laquinimod or a pharmaceutically acceptable salt thereof. 
     
     
         36 . A method of treating a subject suffering from an autoimmune disease-associated ocular inflammation, the method comprising periodic ocular administration to the subject of a therapeutically effective amount of laquinimod or a pharmaceutically acceptable salt thereof effective to treat the subject. 
     
     
         37 . An ocular pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof for use in treating an autoimmune disease-associated ocular inflammation.