Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints
The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of: i) an inhibitor of a pro-inflammatory interleukin; ii) an inhibitor of TNF-α synthesis; iii) an inhibitor of membrane-bound TNF-α; iv) an inhibitor of a natural receptor of TNF-α; v) an inhibitor of NO synthase, vi) an inhibitor of PLA 2 enzyme; vii) an anti-proliferative agent; viii) an anti-oxidant; ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, and x) an inhibitor of MMPs; and xi) an inhibitor of p38 kinase.
1. A method of treating an inflamed orthopedic joint, said joint comprising i) opposing hyaline cartilage articular surfaces, ii) a peripheral collagenous capsule defining a central joint space and iii) synovial fluid contained within the joint space, comprising trans-capsularly administering into the joint space a formulation comprising an effective amount of an anti-TNF-α monoclonal antibody or antigen-binding fragment thereof such that the inflamed orthopedic joint is treated, the method further comprising providing a therapeutically effective amount of a Growth Differentiation Factor (GDF) to the joint.
2. The method of claim 1 , wherein the joint is a knee joint.
3. The method of claim 1 , wherein the joint is a hip joint.
4. The method of claim 1 , wherein the joint is a spinal facet joint.
5. The method of claim 1 , wherein the formulation further comprises a therapeutically effective amount of at least one growth factor.
6. The method of claim 1 , wherein the formulation further comprises a liposomal delivery system.
7. The method of claim 1 , wherein the formulation is administered in an amount of less than 1 cc.
8. The method of claim 1 , wherein the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is present in the formulation in an amount of at least 100 mg/ml.
9. The method of claim 1 , wherein the formulation is provided with a sustained release device.
10. The method of claim 9 , wherein the sustained release device comprises a hydrogel.
11. The method of claim 9 , wherein the sustained release device provides controlled release.
12. The method of claim 9 , wherein the sustained release device provides continuous release.
13. The method of claim 9 , wherein the sustained release device provides intermittent release.
14. The method of claim 9 , wherein the sustained release device comprises microspheres having a plurality of degradation rates.
15. The method of claim 9 , wherein the sustained release device maintains the administered anti-TNF-α monoclonal antibody or antigen-binding fragment thereof at a therapeutically effective level.
16. The method of claim 1 , wherein the formulation is provided closely adjacent to the outer wall of the capsule.
17. The method of claim 1 , wherein the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is present in the formulation in a maximum amount of 0.5 mg.
18. The method of claim 1 , wherein the formulation further comprises a growth factor, which is provided by platelet concentrate.
19. The method of claim 1 , wherein the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof therapeutically inhibits the production of a cytokine.
20. The method of claim 1 , wherein the formulation further comprises viable mesenchymal stem cells.
21. The method of claim 1 , wherein the formulation is injected into the synovial fluid.
22. The method of claim 1 , wherein the formulation includes a viscosupplement.
23. The method of claim 1 , wherein a portion of the synovial fluid is removed prior to administration of the-anti-TNF-α monoclonal antibody or antigen-binding fragment thereof.
24. The method of claim 1 , wherein the administration is performed through a needle.
25. The method of claim 1 , wherein the formulation is administered through a drug pump.
26. The method of claim 1 , wherein the formulation is administered in a volume of between 0.03 ml and 0.3 ml.
27. The method of claim 1 , wherein the administration comprises providing the formulation in a patch attached to an outer wall of the capsule.
28. The method of claim 1 , wherein the administration comprises providing the formulation in a depot at a location closely adjacent an outer wall of the capsule.
29. The method of claim 1 , wherein the administration comprises providing the formulation in a depot at a location closely adjacent to an endplate of an adjacent bony body.
30. The method of claim 1 , wherein the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is predominantly released from the formulation by diffusion of the high specificity antagonist through a sustained delivery device.
31. The method of claim 30 , wherein the sustained delivery device is a polymer.
32. The method of claim 1 , wherein the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is predominantly released from the formulation by biodegradation of a sustained delivery device.
33. The method of claim 1 , wherein the formulation further comprises BMP-1, BMP-3, BMP-2, OP-1, BMP-2A, BMP-2B, or BMP-7.
34. The method of claim 1 , wherein the formulation further comprises TGF-β.
35. The method of claim 1 , wherein said anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is adalimumab.
36. The method of claim 1 , wherein said anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is CDP-571.
37. The method of claim 1 , wherein said anti-TNF-α monoclonal antibody or antigen-binding fragment thereof is CDP-870.
38. A method of treating an inflamed orthopedic joint, said joint comprising i) opposing hyaline cartilage articular surfaces, ii) a peripheral collagenous capsule defining a central joint space and iii) synovial fluid contained within the joint space, comprising trans-capsularly administering into the joint space a formulation comprising an effective amount of infliximab, such that the inflamed orthopedic joint is treated, the method further comprising providing a therapeutically effective amount of a Growth Differentiation Factor (GDF) to the joint.
39. The method of claim 1 , wherein the GDF is provided to the joint simultaneously with the TNF-α antibody or antigen binding fragment thereof.
40. The method of claim 39 , wherein the GDF is provided in the formulation comprising the TNF-α antibody or antigen binding fragment thereof.
41. The method of claim 1 , wherein the GDF is provided to the joint separately from the anti-TNF-α monoclonal antibody or antigen-binding fragment thereof.
42. The method of claim 1 , wherein the joint is in a mammalian subject with ankylosing spondylitis.