Mechanisms of cartilage destruction and novel nonsurgical therapeutic strategies to retard cartilage injury in rheumatoid arthritis.

Abstract:

:Although there are excellent rationales for the use of biologic agents, no published novel therapeutic strategy in patients with early or late rheumatoid arthritis has thus far been proven in controlled clinical studies to prevent or retard cartilage destruction. Although T-cell-specific therapies in chronic rheumatoid arthritis have some success, the percentage of patients responding and the degree of clinical improvement are disappointing, and cartilage injury can neither be prevented nor retarded. Similarly, attempts to interrupt the cytokine loops and inhibit adhesion molecules are only modestly successful. The alternative approach of solely controlling the effector side by direct or indirect metalloproteinase inhibition seems attractive because it would circumvent the cytokine networks while theoretically still preventing the final consequences of inflammation on cartilage. One therapeutic strategy that inhibits metalloproteinses-tetracyclines or chemically transformed tetracyclines-cannot be considered a breakthrough with respect to either reduction of disease activity or prevention or retardation of cartilage injury in rheumatoid arthritis. It is likely that combination therapy will be further developed in the future. The most promising agents today, such as the anti-tumor necrosis factor-alpha antibodies, must be combined with other current strategies as well as with newly developed disease-specific biologic agents. To affect multiple sites in the underlying inflammatory process and to target the delivery of the agents could be one of the goals. The efficacy and effectiveness of any new strategy depends on its ability to alter the function of the aggressive and transformed synovial fibroblasts within the pannus and to protect the articular chondrocytes and early cartilage injury.

journal_name

Curr Opin Rheumatol

authors

Häuselmann HJ

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

241-50

issue

3

eissn

1040-8711

issn

1531-6963

journal_volume

9

pub_type

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