Targeting the immune response: new therapies for rheumatoid arthritis

This review examines the use of new biologic drug treatments in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease, in which the immune system (the body’s defense against disease) begins attacking healthy tissue. This is a chronic (long-term and recurring) disease, therefore the main goal of treatment is remission (a time when the disease is not active and the joints are not being damaged).

 The first treatments used in rheumatoid arthritis include disease-modifying antirheumatic drugs such as methotrexate (Trexell) that block the immune response. Biologic disease-modifying antirheumatic drugs, such as tumor necrosis factor inhibitors, block the activity of proteins such as tumor necrosis factor that lead to inflammation. Both non-biologic and biologic disease-modifying antirheumatic drugs are often combined in rheumatoid arthritis therapy.

 However, roughly 30% of patients do not respond to the first biologic disease-modifying antirheumatic drug tried, or the response to the drug decreases over time. Therefore, efforts have been made to develop new biologic disease-modifying antirheumatic drugs that block other proteins or causes of rheumatoid arthritis. The current review focuses on new biologic disease-modifying antirheumatic drugs in rheumatoid arthritis treatment.

New biologic disease-modifying antirheumatic drugs focus on molecules or proteins other than the previously established targets that play a role in rheumatoid arthritis. For instance, granulocyte-macrophage colony stimulating factor (GM-CSF) receptor alpha, when activated, leads to an increase in white bloods cells, which play a large role in the immune response. Blocking this receptor could decrease the inflammation associated with rheumatoid arthritis. Mavrilimumab is a new treatment that blocks this receptor, and has already been found to be safe and effective. Recent clinical trials have shown that a dose of 100 mg decreased levels of C-reactive protein (a protein that is associated with inflammation). After 12 weeks of treatment with mavrilimumab, 69% of patients saw a 20% improvement in their symptoms versus 40% of patients taking a placebo (a substance that has no effect on the body used as a control). 18% of patients taking mavirilmumab saw a 70% improvement versus 4% of patients taking a placebo.

 As the goal of rheumatoid arthritis treatment is remission, other targets must be identified that can induce a larger response. However, not all immune response targets lead to improvements in rheumatoid arthritis symptoms. For instance, a second biologic disease-modifying antirheumatic drug, tabalumab, inhibits B cells, another important factor in the immune response. This treatment did not lead to significant symptom reduction at any dosage in clinical trials.

While determining new targets for treatment is essential, the optimum control of rheumatoid arthritis will require methods of determining which subset of patients would benefit most from a given treatment. With this type of treatment tailoring, patients will not have to undergo unnecessary therapy with a drug that will not be beneficial.

This review concludes that while new targets for rheumatoid arthritis are being identified, these are likely to represent modest steps forward. True progression will lie in earlier detection of the disease and speedy administration of therapy.