Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study

Abstract

Objective. To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD.Methods. In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score.Results. A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P ‫؍‬ 0.50), 4 and 12 (P ‫؍‬ 0.005), and 11 and 24 (P ‫؍‬ 0.001), respectively.Conclusion. Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.Rheumatoid arthritis (RA) is a chronic, potentially disabling disease characterized by synovial inflammation, with subsequent cartilage and bone destruction leading to joint malalignment. An abundance of evidence indicates the benefits of early intervention with disease-modifying antirheumatic drugs (DMARDs) on the disease course and outcome (1). Some recent studies clearly show that treatment of early RA with combinations of DMARDs is well tolerated and provides better clinical response than treatment with DMARD monoSupported by the Finnish Office for Health Care Technology Assessment.

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

“…For individual patients, the clinical course in the first 2 years after diagnosis is clearly related to the clinical course in the following 3 years. Studies in rheumatoid arthritis show that reaching sustained remission early in the course of disease by using a more aggressive initial treatment is related to an improved radiographic outcome and less joint damage (15)(16)(17). This study shows that a lower percentage of active disease in the first 2 years is related to a mild course of disease afterward.…”

The good initial response to therapy with a combination of traditional disease‐modifying antirheumatic drugs is sustained over time: The eleven‐year results of the Finnish rheumatoid arthritis combination therapy trial

“…If it could be discontinued without losing remission, other DMARDs could be tapered down, 1 DMARD per year, by gradually reducing the dosage. If the RA was reactivated, the last medication and dosage at which remission was maintained was reinstituted (10).…”

“…Effective early therapy with combinations of conventional DMARDs has also been shown to retard the radiologic progression of joint damage in RA patients and, thus, to reduce the probability of chronic disability (9,10). However, the effects of the more aggressive therapy on the long-term prognosis of RA patients are unknown.…”

“…Furthermore, despite the change to an unrestricted treatment strategy after 2 years, less radiologic joint destruction was still present at 5 years (4,10). The good clinical response seen at 6 months in those receiving a combination of conventional DMARDs also translated into better maintenance of working capacity at 5 years (11,12).…”

The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies

“…joint disease (or, early polyarthritis [EPA]) because the more characteristic features, such as bone erosions in RA, appear relatively late in most patients (2)(3)(4)(5)(6). The current emphasis on early treatment of patients with EPA further complicates the issue by preventing or retarding the development of diagnostic features of a specific disease.…”