Rheumatoid arthritis (RA) is a chronic, progressive, systemic, autoimmune disease characterized by joint inflammation and destruction, progressive disability and adverse psychological effects.
This condition places significant health, psychological, emotional, and socioeconomic burdens on both the patient as well as society. There is currently no cure for RA. The purpose of therapy is to control disease activity, reduce signs and symptoms, maintain physical function, optimize quality of life, reduce the rate of joint damage, and, if possible, induce complete remission.
Disease modifying anti rheumatic drugs (DMARDS) partly achieve these goals, but often are inadequate for preventing progressive joint damage, improving quality of life, or intervening with the adverse effects of the disease on internal organs.
In addition, there are often significant problems associated with tolerability and safety.
Newer biologic drugs, such as TNF inhibitors, are more effective, work faster, and halt or slow joint damage. The use of these drugs has revolutionized our approach to therapy and has actually produced sustained remission in many patients.
In patients for whom TNF inhibitors fail to work or stop working, second line biologic therapies are used.
Unfortunately, use of biologic therapies is limited by the inconvenience of required subcutaneous or intravenous routes of administration and loss of efficacy with continued use in a significant number of patients.
Therefore, there has been great interest in the development of drug treatments that are more effective than the current biologic drugs, but have less toxicity than the older DMARDS, while being able to be given via the oral route.
The target that has excited biotech scientists are protein kinases. These are proteins that have an effect on signaling of cytokines. Cytokines are messenger proteins that are important for the activation, growth, and multiplication of cells called lymphocytes, that govern immune response. In essence, if you block protein kinases you also block the cytokine pathway that permits signaling from the surface of the cell to the nucleus.
In particular, during chronic inflammatory disease states, protein kinases are the major means of communication for cytokines within cells.
By blocking these messengers, various drugs termed “protein kinase inhibitors” are able to produce excellent clinical response in patients with RA. The two major targets that are being evaluated currently are JAK kinase and Syk kinase.
These protein kinases inhibit multiple cytokine pathways and are a rational target as a treatment for diseases where lymphocyte activation and multiplication play a major role.
Besides rheumatoid arthritis, protein kinase inhibitors are being evaluated in organ transplantation, inflammatory bowel disease, and psoriasis. Other conditions are under study as well.
The data so far in clinical trials is encouraging with response scores similar to that found with TNF inhibitors.
The question then becomes when do you use these medicines? Other questions also need to be answered. Do you use them alone or with methotrexate? What happens if you use them with biologics? When is the best time to use these medicines? Is it possible to cure RA with these drugs?
Hopefully the answers to these questions will be answered shortly.
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