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Treatment of early rheumatoid arthritis

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Abstract

Increasing attention has focused on the early treatment of rheumatoid arthritis (RA) because of the short time lag that can exist between the onset of synovitis and the development of joint damage and loss of function. For optimal benefit, treatment may need to begin in a theoretical ‘window of opportunity’ that exists within the first few weeks or months of disease onset. Current evidence suggests that early introduction of therapy with disease-modifying antirheumatic drugs (DMARDs) can slow the progression of joint damage and improve long-term outcomes. Moreover, results of several studies suggest that early treatment with two- and three-DMARD combinations can produce superior benefits compared with DMARD monotherapy. Although early DMARD therapy has proven ability to slow the pace of joint destruction, individual treatment decisions are problematic because of the difficulty in accurately predicting individual prognosis and differential responses to therapy. Controlled trials are needed in early disease to investigate these questions and to identify treatment strategies that can effectively induce sustained remission and prevent joint damage.

Section snippets

Rationale for aggressive therapy

Rheumatoid arthritis (RA) is a significant cause of disability, functional loss1 and increased mortality.2., 3. However, many clinicians believe the prognosis is improving with the growing repertoire of disease-modifying antirheumatic drugs (DMARDs) and more aggressive approaches to therapy. The new DMARDs expand treatment options. The approval of leflunomide, the tumour necrosis factor (TNF)-α blockers (etanercept, infliximab, adalimumab), and the interleukin-1 (IL-1) receptor antagonist,

Finding the best DMARD strategy: prospects for early intervention

Finding the best DMARD treatment for early RA is a multi-faceted issue. The appropriate timing of early treatment is uncertain and the so-called ‘window of opportunity’ remains only a theoretical concept.13 Diagnostic and prognostic uncertainties in the early symptomatic stages of RA must be appropriately balanced with the potential damaging consequences of delaying therapy. If urgency is critical to effective management of early RA, then patients with recent-onset arthritis must gain ready

Definition of early RA

While the 1987 American College of Rheumatology (ACR) classification criteria for RA16 allow for a uniform definition of established disease, they do not serve the same purpose in the early symptomatic stages. Classification criteria currently do not exist for early RA, and with a disease duration of <12 months, the current ACR criteria are relatively insensitive for identifying patients who ultimately will develop persistent, erosive disease.17 Inflammatory arthritis that cannot be classified

Early versus delayed DMARD therapy

Only a few studies have been specifically designed to compare the potential benefits of early DMARD therapy with a more deliberate, or delayed, approach (see Table 1). To this end, van der Heide et al performed a 12-month open randomized trial comparing the outcomes of patients who began treatment with a non-steroidal anti-inflammatory drug (NSAID) with those who were initially treated with a DMARD.19 The study included 238 patients with RA whose duration of disease was less than 12 months and

Head-to-head comparisons: Is any DMARD better than another?

Although the evidence calls for prompt initiation of DMARD therapy in the early stages of RA, uncertainty remains about the best DMARD or combination to use in this situation. In clinical practice, methotrexate is often the DMARD of first choice for patients with moderate-to-severe disease. Sulphasalazine is another frequently chosen agent. Hydroxychloroquine may be considered for initial treatment of patients with mild disease. However, which DMARD, if any, to use in the individual patient is

Combination DMARD therapy

Mounting evidence indicates that combination DMARD therapy can produce greater clinical efficacy than DMARD monotherapy without substantially increasing toxicity.37., 38., 39., 40., 41., 42., 43. A few studies have investigated the potential value of combination therapy in early disease (see Table 2). In the FIN-RACo (Finish Rheumatoid Arthritis Combination Therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomized to receive a combination of sulphasalazine,

Corticosteroids

Daily oral corticosteroids in doses of 5–10 mg/day have been used primarily for symptomatic control of RA. In a meta-analysis, Saag et al found that treatment with low doses of oral corticosteroids improves various measures of disease activity.49 The extent of clinical efficacy was nearly equivalent to that of some of the conventional DMARDS, such as methotrexate and sulphasalazine. Thus, low doses of oral corticosteroids can control synovitis to a clinically significant degree and are useful

Whom do we treat aggressively?

Although physicians may agree about the value of starting DMARD therapy in the early stages of RA, they would probably debate the urgency of intervention and the question of which patient, if any, should be treated aggressively at the outset of disease. By the time a patient reaches a rheumatologist, many already have persistent synovitis and are functioning suboptimally in their home or work environment. The course of the disease shows considerable variability. Some patients with RA may have

Recommendations

Questions about the best DMARD therapy for early RA cannot be resolved with the current evidence. Some consensus has been reached on the positive value of early introduction of DMARD therapy, and increasing evidence suggests that combination therapy at this stage can produce long-lasting benefits on radiological outcomes. However, well-designed studies have not clarified the relative value of beginning with single or combination DMARD therapy. Presently, most patients with early RA who have

Summary

Effective early treatment of RA depends on prompt diagnostic evaluation and initiation of appropriate DMARD therapy. Treatment decisions are made with the knowledge that early inflammatory arthritis can spontaneously remit or persist with or without a destructive component. Importantly, the disease evolves rapidly to a destructive phenotype in a substantial proportion of patients with RA, providing much of the rationale for early aggressive therapy. However, prognostic information is not

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