Rheumatoid arthritis is a chronic and debilitating disease, affecting an estimated 1% of the population worldwide. The past decade has witnessed an explosion in our understanding of the pathophysiology of rheumatoid arthritis and therefore in our ability to more effectively target the disease process. Although a cure remains elusive, remission is an approachable goal. There has been a complete remodeling of the traditional pyramid by rheumatologists, who now treat rheumatoid arthritis earlier and more aggressively than ever before. Standard single therapy with disease-modifying antirheumatic drugs, which was previously the final step in treating rheumatoid arthritis, is now practically bypassed in the deluge of information suggesting that combinations of disease-modifying antirheumatic drugs or newer biologic therapy is more effective. It is difficult to assimilate all the data and develop a rational approach; however, the bottom line is often the deciding factor: the newer agents are tremendously expensive. The intent of this article is to review recent and relevant trials in the treatment of rheumatoid arthritis, suggest a treatment algorithm, and argue that traditional disease-modifying antirheumatic drugs continue to play a pivotal role.
Abbreviations:ACR American College of Rheumatology, DMARDs disease-modifying antirheumatic drugs, FDA Food and Drug Administration, HCQ hydroxychloroquine, RA rheumatoid arthritis, MTX methotrexate, NSAIDs nonsteroidal antiinflammatory drugs, SSZ sulfasalazine, TNF tumor necrosis factor, IL interleukin
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease of unknown cause, which leads to crippling disability, loss of function, and premature mortality [1]. An estimated 1% of the population is affected worldwide, and unfortunately there is no cure [2]. Therefore, the current goal is to achieve and maintain remission with disease-modifying antirheumatic drugs (DMARDs) before irreversible joint destruction occurs.
Although the trigger for RA remains elusive, the past decade has witnessed an explosion in the understanding of the pathophysiology of RA, leading to the development of novel therapeutic approaches [3•]. The efficacy of early initiation of DMARD therapy (eg, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) has gained almost universal acceptance; gone are the days of physician frustration with the traditional pyramid approach: giving NSAIDs and steroids until joint deformity or radiographic progression is evident, and then stepping up to DMARDs [4,5]. As recently as 1997, Benson et al. [6] proposed a novel therapeutic pyramid based on early rheumatologic evaluation and aggressive institution of DMARDs. Further studies have shown that combinations of DMARDs are more effective than monotherapy [7-10]. Most recently, the development of biologic response modifiers, targeting specific cytokines that play a major role in perpetuating the inflammation of RA-tumor necrosis factor-α (TNF-α) [etanercept, infliximab, and adalimumab]) and interleukin (IL)-1 (anakinra)-have been shown to be effective therapies [11-16]. Several other biologic products currently under investigation target other cytokines (IL-6), T cell activation (anti-CTLA4-Ig), and B cells (anti-CD20-Rituxumab) [17-19]. Once again, frustration reigns, but from a fundamentally different perspective: when one is faced with many viable options and a scarcity of data comparing them, which one should be chosen? The intent of this article is to provide a brief review of the relevant studies in the treatment of rheumatoid arthritis to date (Table 1) and to address the role of traditional DMARDs.