The road forward: the scientific basis for tetracycline treatment of arthritic disorders.

The potential role of a collagenase inhibitor for treatment of arthritis was recognized almost immediately after the discovery of vertebrate collagenase. Yet despite vast efforts from the pharmaceutical industry, no such drug has been approved for such use by a regulatory agency. Although two semisynthetic antimicrobial tetracyclines, viz. minocycline and doxycycline, have been shown to have modest clinical benefits in over a dozen trials in rheumatoid arthritis, neither drug is in widespread use. The almost universal use of methotrexate and the rapid development of potent biologic agents have eclipsed the potential usage of TETs for RA. Ironically, it is in osteoarthritis, where there has only been one clinical trial which essentially failed, that the best potential exists for use of an MMP-inhibiting TET.