Autoimmune Rheumatic diseases
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin and disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate have been the mainstay treatments for rheumatoid arthritis for decades. In the past few years, anti-TNF-α (tumor necrosis factor-α) biopharmaceuticals have sparked a revolution. More drugs targeting the inflammation pathway are in the works.
There are a large number of diseases involving inappropriate activation of the immune system. These are often classified as immune-mediated diseases and include autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis, and type I diabetes mellitus, allergic diseases such as asthma, and immune-mediated graft/organ rejection. RA is a chronic systemic inflammatory disease involving the destruction of articular cartilage and bone in joints.
Despite the advances in our understanding of RA, the cause remains elusive. It is now recognized that there are two arms to the disease, namely an inflammatory arm and a destructive arm. The inflammation causes many of the symptoms of pain and swelling whereas the joint destruction is the major cause of long term disability associated with this disease. It is clear that the joint destruction occurs early in the course of the disease and mediators, such as cytokines (non-antibody proteins that act as intracellular mediators), are important in this process.
Since the birth of the modern pharmaceutical industry just over 100 years ago, with the synthesis of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay treatment of RA. It is generally accepted that NSAIDs relieve the symptoms, such as pain and swelling, without changing the course of the underlying disease. There have been considerable efforts to develop drugs, which will modify the disease progress. These so-called disease-modifying anti-rheumatic drugs (DMARDs) have met with variable success. DMARDs such as cyclosporine or methotrexate, while effective, can have major adverse effects. Furthermore, continued DMARD therapy is generally required as there is the significant risk of a disease flare if treatment is stopped.
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