Compositions and methods for treating inflammatory arthritis

Abstract

Methods for treating or preventing one or more symptoms of rheumatoid arthritis or other types of inflammatory arthritis involves administering a formulation containing an effective amount of arsenic trioxide to an affected patient. The arsenic trioxide formulation can be administered orally, for example, as a solution, suspension, syrup, emulsion, tablet, or capsule.

1 - 9 . (canceled) 
     
     
         10 . A pharmaceutical formulation for treating one or more symptoms of rheumatoid arthritis or other inflammatory arthritis in a subject comprising an effective amount of arsenic trioxide sufficient to cause degradation of IL-6 receptor by degrading the gp130 subunit without causing degradation of the IL-6 receptor a subunit of the IL-6 receptor expressed in fibroblast-like synoviocytes in the subject with arthritis, and, optionally, a pharmaceutically acceptable excipient. 
     
     
         11 . The pharmaceutical formulation of  claim 10 , wherein the arsenic trioxide is in a pharmaceutically acceptable carrier for oral administration. 
     
     
         12 . The pharmaceutical formulation of  claim 10 , wherein the arsenic trioxide is in a pharmaceutically acceptable carrier for local administration to a synovial joint. 
     
     
         13 . The pharmaceutical formulation of  claim 10 , wherein the arsenic trioxide is present in an amount from 1 mg to 10 mg. 
     
     
         14 . The pharmaceutical formulation of  claim 13 , wherein the arsenic trioxide is present in an amount from 5 mg to 10 mg. 
     
     
         15 . The pharmaceutical formulation of  claim 10  in a unit dosage form for oral administration, wherein the unit dosage form is selected from the group consisting of solutions, suspensions, emulsions, syrups, tablets and capsules. 45288370 6 UHK 00315 DIV 095225/00095 
     
     
         16 . The pharmaceutical formulation of  claim 10  further comprising a steroidal or non-steroidal anti-inflammatory agent. 
     
     
         17 . The pharmaceutical formulation of  claim 10 , wherein the amount of arsenic trioxide is sufficient to cause reduction of proliferation of fibroblast-like synoviocytes in the subject with arthritis by a caspase-independent pathway. 
     
     
         18 . The pharmaceutical formulation of  claim 10 , wherein the amount of arsenic trioxide is sufficient to cause the degradation of IL-6 receptor by degrading the gp130 subunit without causing degradation of the IL-6 receptor a subunit of the IL-6 receptor expressed in fibroblast-like synoviocytes in the subject with arthritis and reduction of proliferation of fibroblast-like synoviocytes in the subject with arthritis. 
     
     
         19 . The pharmaceutical formulation of  claim 10 , wherein the amount of arsenic trioxide is adjusted lower according to kidney function of the subject with arthritis. 
     
     
         20 . The pharmaceutical formulation of  claim 10 , wherein the degradation of the IL-6 receptor comprises degrading component gp130 of the IL-6 receptor by at least 20% when compared to the level of gp130 of the IL-6 receptor expressed in fibroblast-like synoviocytes of the subject with arthritis before administration of the oral dosage unit of arsenic trioxide. 
     
     
         21 . The pharmaceutical formulation of  claim 10 , wherein the degradation is via mono-ubiquitination of the gp130 subunit of the IL-6 receptor expressed in the fibroblast-like synoviocytes in the subject with arthritis. 
     
     
         22 . The pharmaceutical formulation of  claim 10 , wherein the amount of arsenic trioxide causes mono-ubiquitination of the gp130 subunit of the IL-6 receptor and its degradation via the lysosomal pathway in the fibroblast-like synoviocytes in the subject with arthritis. 
     
     
         23 . A pharmaceutical formulation for treating one or more symptoms of rheumatoid arthritis or other inflammatory arthritis in a subject comprising an effective amount of arsenic trioxide sufficient to cause reduction of proliferation of fibroblast-like synoviocytes in the subject with arthritis by a caspase-independent pathway. 
     
     
         24 . The pharmaceutical formulation of  claim 23 , wherein the amount of arsenic trioxide is effective to inhibit fibroblast-like synoviocyte cell proliferation via a caspase-independent and IL-6 receptor-dependent pathway.