Early rheumatoid arthritis: a medical emergency?

In this issue of The American Journal of Medicine, Lard et al. (1) report that early treatment (within 2 weeks of diagnosis) of patients with rheumatoid arthritis provides better outcomes at 2 years of disease than does delayed treatment, and they conclude that both patients and physicians should consider early-onset rheumatoid arthritis as a medical emergency. Their study corroborates previous reports on the benefit of early management of the disease (2– 4). If one accepts the argument that the acute and chronic consequences of rheumatoid arthritis (joint swelling, joint damage, and loss of function) are due to persistent, inadequately controlled inflammation, then control of the abnormal inflammatory process is the fundamental step in managing all patients with the disease. Clearly, a goal of early management is to eliminate symptoms while returning the patient to normal physical and vocational function with structurally normal joints. However, we can hope to achieve this objective only by treating at the onset of the disease, before irreversible cartilage damage has occurred. Long-term observational studies have confirmed the association between inadequately controlled chronic inflammation leading to joint destruction and progressive functional decline. The current treatment goals are to decrease the costs associated with joint arthroplasty, hospitalization, and disability, and to prevent the diminished quality of life and premature mortality. Before the early 1990s, a major reason for delaying the initiation of “second-line therapies,” or disease-modifying antirheumatic drugs (DMARDs), was the misconception that rheumatoid arthritis was a benign disease and that many DMARDs were prohibitively toxic. We now know that rheumatoid arthritis is not innocuous and that many DMARDs are well tolerated and not invariably associated with serious adverse events. In addition to its considerable associated morbidity and economic cost, rheumatoid arthritis leads to premature mortality (5), reducing average life expectancy by approximately 10 years. Furthermore, the indirect costs (primarily work-related disability) are at least twice as high as those of direct patient costs, leading to total disease-related losses of approximately $26 to $36 billion annually in the United States (6). Because rheumatoid arthritis is a chronic disease that often begins at a young age and persists for the lifetime of the patient, its management varies among patients depending on the aggressiveness of the disease; the specific joints involved; and the patient’s age and lifestyle, physical function level, work disability, and social and emotional support. Although compelling data are emerging that suggest that early treatment with DMARDs provides better short-term and perhaps better long-term outcomes (2– 4,7–9), several questions remain. Which patients should be treated early and aggressively? What is the best therapy in the early course of the disease? How can we encourage the referral of patients with earlyonset rheumatoid arthritis to rheumatologists who are experienced with recently approved state-of-the-art treatments? Signs that a marked change in treatment strategy might be warranted began with reports in the late 1980s and early 1990s on the increased mortality associated with rheumatoid arthritis. In the early 1990s, several clinical investigators in Europe developed early-arthritis clinics to establish the diagnosis of rheumatoid arthritis promptly, to optimize patient function as quickly as possible, to suppress acute inflammation, and to institute early therapy with DMARDs. These clinics have also served to establish important inception cohorts. Analysis of these cohorts after at least 10 to 15 years of follow-up may allow us to determine whether earlier, more aggressive care has made an impact on the morbidity and mortality associated with this disease. The article by Lard et al. (1) involves patients from one of these early-arthritis clinics. There are several options for treating a patient with early-onset rheumatoid arthritis who does not respond to nonsteroidal anti-inflammatory drugs (NSAIDs). These include traditional DMARDs such as hydroxychloroquine (or chloroquine), sulfasalazine (or salazopyrine), gold salts, and methotrexate, and newer agents such as leflunomide and the tumor necrosis factor inhibitors etanercept and infliximab. Recent data suggest that treatment with a combination of DMARDs is more effective than monotherapy (2,10). Leflunomide, etanercept, infliximab, cyclosporine, and sulfasalazine, used in combination with methotrexate, are more effective than methotrexate alone for patients initially treated with methotrexate but who had an incomplete response (11). Because of the lack of randomized controlled trials comparing these combination therapies, however, we have insufficient data to decide which agent might be most effective combined with methotrexate. Factors influencing choice of treatment are the patient’s disease activity, functional status (ability to perform activities of daily livAm J Med. 2001;111:498 –500. From the Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama. Requests for reprints should be addressed to Larry W. Moreland, MD, University of Alabama at Birmingham, 1717 6th Avenue South, SRC 068, Birmingham, Alabama 35294-7201.