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Early Rheumatoid Arthritis

Authors: Kate L. Mitchell, MD ; David S. Pisetsky, MDFaculty and Disclosures


Abstract and Introduction


Purpose of Review: Rheumatoid arthritis is a chronic inflammatory disease in which early aggressive therapy with disease-modifying antirheumatic drugs can improve outcome and prevent joint damage. While such therapy is effective, its application can be limited by diagnostic uncertainty in patients with early inflammatory arthritis and concerns about treatment of patients whose disease would remit spontaneously. The purpose of current research is therefore to identify prognostic markers of early disease and to determine the role of aggressive treatment strategies in inducing remission in such patients.
Recent Findings: Recent research has provided new information on genetic markers predicting rapid progression of joint destruction; the role of serology, in particularly, antibodies to citrullinated peptides in diagnosing rheumatoid arthritis; the utility of radiographic techniques in detecting both early synovitis and bone erosion; and the value of combination therapy in controlling signs, symptoms and radiographic progression. Recent clinical studies support the efficacy of a combination of methotrexate with a biological agent, especially a tumor-necrosis-factor blocker, in reducing disease activity.
Summary: While current treatment approaches can produce significant benefits in patients with early arthritis, future investigation is needed to target therapy more selectively and to determine which patients respond best to various agents or combinations.


Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation and destruction in association with serological evidence of autoreactivity. This disease affects approximately 1% of the population and causes significant morbidity and mortality, with accelerated atherosclerosis impairing life expectancy. In the past two decades, the therapy of RA has undergone revolutionary change, reflecting a paradigm shift in treatment approach as well as the introduction of new disease-modifying antirheumatic drugs (DMARDs), most prominently the biological agents, including the tumor-necrosis-factor (TNF) blockers.[1,2]

At the heart of the paradigm shift has been the replacement of gradualism in therapy with an aggressive approach based on the rapid institution of DMARDs (alone or in combination) to achieve a remission or at least a state of low disease activity. As shown in several studies, the outcome of RA can be significantly improved by treatments to reduce disease activity, with early treatment leading to greater benefits.[3-7] Given the efficacy of the new agents and the potency of combination therapy, investigators have questioned whether the induction of long-term remission can be achieved by starting DMARD therapy soon after symptom onset, indeed, as soon as the patient is first evaluated and the diagnosis established. These ideas have been codified into the so-called window-of-opportunity hypothesis which posits that, early in its course, RA displays a unique phenotype in which immunoregulatory disturbances can be decisively or permanently blocked.[8] This review will consider recent studies related to this important topic in the diagnosis and treatment of RA.

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