Delayed-Release Glucocorticoid treatment of Rheumatoid Disease

Abstract

The present invention refers to the treatment of a rheumatic disease and/or osteoarthritis by administering a delayed-release dosage form of a glucocorticoid to a subject in need thereof.

1 . A method for the treatment of a patient suffering from signs and symptoms of an underlying rheumatic disease and/or osteoarthritis, which comprises administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks.  
     
     
         2 . The method of  claim 1 , wherein the treatment comprises administration of the glucocorticoid for at least about four weeks.  
     
     
         3 . The method of  claim 2 , wherein the treatment comprises administration of the glucocorticoid for at least about eight weeks.  
     
     
         4 . The method of  claim 3 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve weeks.  
     
     
         5 . The method of  claim 4 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve months.  
     
     
         6 . The method of  claim 1 , wherein the glucocorticoid dose is greater than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, at the initiation of the therapy.  
     
     
         7 . The method of  claim 1 , wherein the glucocorticoid dose is equal or less than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, for maintenance therapy.  
     
     
         8 . The method of  claim 1 , wherein the rheumatic disease is rheumatoid arthritis, ankylosating spondylitis and/or polymyalgia rheumatica.  
     
     
         9 . The method of  claim 1 , wherein said patient has not previously been treated with an oral immediate release glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         10 . The method of  claim 1 , wherein said patient has previously undergone treatment with an agent selected from a oral immediate release dosage form of a glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         11 . The method of  claim 10 , wherein said patient is refractory to said treatment with an oral immediate release dosage form of a glucocorticoid.  
     
     
         12 . The method of  claim 10 , wherein the immediate release dosage form of a glucocorticoid is replaced by the delayed release dosage form.  
     
     
         13 . The method of  claim 1 , which further comprises administering to said patient an effective amount of a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         14 . The method of  claim 1 , wherein said treatment consists essentially of administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks.  
     
     
         15 . The method of  claim 1 , wherein the delayed-release dosage form has a lag time of from about 2 hours to about 6 hours after administration.  
     
     
         16 . The method of  claim 1 , wherein the delayed-release dosage form has a lag time of from about 3 hours to about 5 hours after administration.  
     
     
         17 . The method of  claim 1 , wherein the delayed-release dosage form has a dissolution time of equal to or less than about 2 hours after the lag time is reached.  
     
     
         18 . The method of  claim 1 , wherein the delayed-release dosage form has a drug release behaviour which is independent of pH.  
     
     
         19 . The method of  claim 1 , wherein the delayed release dosage form is a tablet or a capsule.  
     
     
         20 . The method of  claim 1 , wherein the delayed-release dosage form comprises a non-soluble/non-swellable coating and a core comprising the active agent and a disintegrant and/or a swelling agent.  
     
     
         21 . The method of  claim 1 , wherein the glucocorticoid is cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, budesonide, dexamethasone, fludrocortisone, fluocortolone, cloprednole, deflazacort, triamcinolone, or the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         22 . The method of  claim 21 , wherein the glucocorticoid is prednisone, prednisolone, methylprednisolone, dexamethasone, fluocortolone, cloprednole, and deflazacort or the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         23 . The method of  claim 1 , wherein said delayed-release dosage form is effective at a lower dose of glucocorticoid as compared to the administration of said glucocorticoid in an immediate release dosage form.  
     
     
         24 . The method of  claim 1 , wherein said patient suffers from inflammation.  
     
     
         25 . The method of  claim 1 , wherein the glucocorticoid is administered in the evening.  
     
     
         26 . The method of  claim 25 , wherein the glucocorticoid is administered between about 9:00 pm and about 11:00 pm.  
     
     
         27 . A method for the treatment of a patient suffering from morning stiffness and pain due to an underlying rheumatic disease and/or osteoarthritis, which comprises administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks.  
     
     
         28 . The method of  claim 27 , wherein the treatment comprises administration of the glucocorticoid for at least about four weeks.  
     
     
         29 . The method of  claim 27 , wherein the treatment comprises administration of the glucocorticoid for at least about eight weeks.  
     
     
         30 . The method of  claim 27 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve weeks.  
     
     
         31 . The method of  claim 27 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve months.  
     
     
         32 . The method of  claim 27 , wherein the glucocorticoid dose is greater than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, at the initiation of the therapy.  
     
     
         33 . The method of  claim 27 , wherein the glucocorticoid dose is equal or less than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, for maintenance therapy.  
     
     
         34 . The method of  claim 27 , wherein the rheumatic disease is rheumatoid arthritis, ankylosating spondylitis and/or polymyalgia rheumatica.  
     
     
         35 . The method of  claim 27 , wherein said patient has not previously been treated with an oral immediate release glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         36 . The method of  claim 27 , wherein said patient has previously undergone treatment with an agent selected from a oral immediate release dosage form of a glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         37 . The method of  claim 36 , wherein said patient is refractory to said treatment with an oral immediate release dosage form of a glucocorticoid.  
     
     
         38 . The method of  claim 36 , wherein the immediate release dosage form of a glucocorticoid is replaced by the delayed release dosage form.  
     
     
         39 . The method of  claim 27 , which further comprises administering to said patient an effective amount of a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         40 . The method of  claim 27 , wherein said treatment consists essentially of administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks.  
     
     
         41 . The method of  claim 27 , wherein the delayed-release dosage form has a lag time of from about 2 hours to about 6 hours after administration.  
     
     
         42 . The method of  claim 27 , wherein the delayed-release dosage form has a lag time of from about 3 hours to about 5 hours after administration.  
     
     
         43 . The method of  claim 27 , wherein the delayed-release dosage form has a dissolution time of equal to or less than about 2 hours after the lag time is reached.  
     
     
         44 . The method of  claim 27 , wherein the delayed-release dosage form has a drug release behaviour which is independent of pH.  
     
     
         45 . The method of  claim 27 , wherein the delayed release dosage form is a tablet or a capsule.  
     
     
         46 . The method of  claim 27 , wherein the delayed-release dosage form comprises a non-soluble/non-swellable coating and a core comprising the active agent and a disintegrant and/or a swelling agent.  
     
     
         47 . The method of  claim 27 , wherein the glucocorticoid is cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, budesonide, dexamethasone, fludrocortisone, fluocortolone, cloprednole, deflazacort, triamcinolone, or the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         48 . The method of  claim 47 , wherein the glucocorticoid is prednisone, prednisolone, methylprednisolone, dexamethasone, fluocortolone, cloprednole, and deflazacort and the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         49 . The method of  claim 27 , wherein said delayed-release dosage form is effective at a lower dose of glucocorticoid as compared to the administration of said glucocorticoid in an immediate release dosage form.  
     
     
         50 . The method of  claim 27 , wherein said patient suffers from inflammation.  
     
     
         51 . The method of  claim 27 , wherein the glucocorticoid is administered in the evening.  
     
     
         52 . The method of  claim 51 , wherein the glucocorticoid is administered between about 9:00 pm and about 11:00 pm.  
     
     
         53 . A method for the treatment of a patient having circadian fluctuations in Interleukin 6 levels due to underlying inflammation, which comprises administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks, and wherein said treatment is administered such that the glucocorticoid is released at or before the time when the patient's Interleukin 6 level is at a daily peak.  
     
     
         54 . The method of  claim 53 , wherein said peak Interleukin 6 level occurs during the night.  
     
     
         55 . The method of  claim 53 , wherein the fluctuating Interleukin 6 levels are caused by a rheumatic disease or asthma.  
     
     
         56 . The method of  claim 55 , wherein the rheumatic disease is selected from the group consisting of rheumatoid arthritis, ankylosating spondylitis, polymyalgia rheumatica, asthma and combinations thereof.  
     
     
         57 . The method of  claim 53 , wherein the treatment comprises administration of the glucocorticoid for at least about four weeks.  
     
     
         58 . The method of  claim 53 , wherein the treatment comprises administration of the glucocorticoid for at least about eight weeks.  
     
     
         59 . The method of  claim 53 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve weeks.  
     
     
         60 . The method of  claim 53 , wherein the treatment comprises administration of the glucocorticoid for at least about twelve months.  
     
     
         61 . The method of  claim 53 , wherein the glucocorticoid dose is greater than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, at the initiation of the therapy.  
     
     
         62 . The method of  claim 53 , wherein the glucocorticoid dose is equal or less than about 10 mg/day of prednisone, or an equivalent amount of another glucocorticoid, for maintenance therapy.  
     
     
         63 . The method of  claim 53 , wherein said patient has not previously been treated with an oral immediate release glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         64 . The method of  claim 53 , wherein said patient has previously undergone treatment with an agent selected from a oral immediate release dosage form of a glucocorticoid, a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         65 . The method of  claim 64 , wherein said patient is refractory to said treatment with an oral immediate release dosage form of a glucocorticoid.  
     
     
         66 . The method of  claim 64 , wherein the immediate release dosage form of a glucocorticoid is replaced by the delayed release dosage form.  
     
     
         67 . The method of  claim 53 , which further comprises administering to said patient an effective amount of a NSAID, a DMARD, a TNFα inhibitor, an IL-1 inhibitor, an IL-6 inhibitor, an analgetic agent, or combinations thereof.  
     
     
         68 . The method of  claim 53 , wherein said treatment consists essentially of administering to said patient an effective amount of a glucocorticoid contained in a delayed-release dosage form, wherein said treatment is administered once daily for at least about two weeks.  
     
     
         69 . The method of  claim 53 , wherein the delayed-release dosage form has a lag time of from about 2 hours to about 6 hours after administration.  
     
     
         70 . The method of  claim 53 , wherein the delayed-release dosage form has a lag time of from about 3 hours to about 5 hours after administration.  
     
     
         71 . The method of  claim 53 , wherein the delayed-release dosage form has a dissolution time of equal to or less than about 2 hours after the lag time is reached.  
     
     
         72 . The method of  claim 53 , wherein the delayed-release dosage form has a drug release behaviour which is independent of pH.  
     
     
         73 . The method of  claim 53 , wherein the delayed release dosage form is a tablet or a capsule.  
     
     
         74 . The method of  claim 53 , wherein the delayed-release dosage form comprises a non-soluble/non-swellable coating and a core comprising the active agent and a disintegrant and/or a swelling agent.  
     
     
         75 . The method of  claim 53 , wherein the glucocorticoid is cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, budesonide, dexamethasone, fludrocortisone, fluocortolone, cloprednole, deflazacort, triamcinolone, or the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         76 . The method of  claim 75 , wherein the glucocorticoid is prednisone, prednisolone, methylprednisolone, dexamethasone, fluocortolone, cloprednole, and deflazacort or the corresponding pharmaceutically acceptable salts and/or esters thereof.  
     
     
         77 . The method of  claim 53 , wherein said delayed-release dosage form is effective at a lower dose of glucocorticoid as compared to the administration of said glucocorticoid in an immediate release dosage form.  
     
     
         78 . The method of  claim 53 , wherein the glucocorticoid is administered in the evening.  
     
     
         79 . The method of  claim 78 , wherein the glucocorticoid is administered between about 9:00 pm and about 11:00 pm.