From ATLANTA Medicine, 2014, Vol. 85, No. 3
Rheumatoid Arthritis (RA) is the prototypical autoimmune arthritis. It’s a rheumatologic illness with the most immune targeted therapies.
In the late 1990s, TNF inhibitors were introduced and marked the advent of targeted biologic therapy for RA. The evolution of therapy for rheumatoid arthritis has been from symptomatic treatment to relatively unfocused disease modifying anti-rheumatic (DMARD) therapy, and presently to biologic and small molecule therapies that target particular proteins important in the inflammatory process.
As understanding of the immune process has improved, so have the tools for treatment, diagnosis and monitoring. The 1987 American College of Rheumatology (ACR) criteria uses the Rheumatoid Factor (RF) and Erythrocyte Sedimentation Rate (ESR) lab tests to help diagnose RA. The 2010 EULAR/ACR Criteria added tests for C-reactive protein (CRP) and anticitrullinated peptide /protein antibodies.
Anticitrullinated peptides/protein antibodies can be present years before the onset of arthritis, and they have been demonstrated to have a high diagnostic specificity and a high positive predictive value for RA.(1) Understanding of citrulline immunity could ultimately lead to new therapies and possibly prevention of RA.(2)
Differences in immune response to stress may help in understanding rheumatologic conditions. For instance, patients with RA have been shown to have higher stress-induced levels of IL-1b and IL-2 compared to patients with psoriasis and healthy controls.(3) It has been shown that cell immunity associated with cytomegalovirus (CMV) exposure influences the clinical response to DMARD therapy in RA. The suggestion is that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly outcomes in RA.(4)
The advent of anti-TNF therapy brought on the renaissance of rheumatology; however, anti-TNF therapy can unexpectedly trigger the onset or exacerbate multiple sclerosis (MS). This is thought to be related to the balance of regulatory T-cells (Tregs) and effector T-cells (Teffs). A better understanding these differential effects of TNF on Teffs and Tregs may lead to safer and more effective anti-TNF therapies.(5)
RA is considered to be a complex genetic disease characterized by genetic factors with environmental triggers. New insights from DNA sequence-based analysis of gut microbial communities suggest a possible role for the microbiota in the pathogenesis of RA.(6) It has been proposed that the step beyond therapy is to induce immune tolerance in the treatment of rheumatoid arthritis.(7)
More confident diagnoses and better understanding of the immune process have led to more effective therapies and allowed the opportunity to tailor therapy in such a way as to achieve low disease activity, commonly referred to as Treat to Target. Years ago we referred to our therapies as remittive; however, they were more properly Disease Modifying. Clearly, our goal is to attain 100 percent improvement; however, until we can reach that goal, we will strive for the greatest improvement.
It is clear that immune modulation can in some cases place patients in a clinical remission; however, combined therapy with biologic response modifiers has resulted in unacceptable side effects. At this juncture a combination of a conventional DMARD therapy with a Biologic Response Modifier seems to give the best opportunity to preserve joint architecture in this chronic inflammatory erosive arthritis. It is exciting to be on the cusp of real understanding and meaningful therapies for one of the most disabling medical conditions.