Objective. Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients.Methods. In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of <2.4).Results. Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P ‫؍‬ 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups.Conclusion. In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.Over the last 2 decades, the treatment of patients with rheumatoid arthritis (RA) has changed considerably. Currently, the goal of therapy is not only symptom

Currently available antirheumatic drugs can be highly effective in patients with early rheumatoid arthritis in a setting of tight disease control. Initial combination therapies seem to provide earlier clinical improvement and less progression of joint damage, but all treatment strategies eventually showed similar clinical improvements. In addition, combination therapy can be withdrawn successfully and less treatment adjustments are needed than with initial monotherapies.

The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice.

Objective. To determine associations of methotrexate (MTX) efficacy and toxicity with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway enzymes in patients with early rheumatoid arthritis (RA).Methods. Patients (n ‫؍‬ 205) with active RA received MTX at an initial dosage of 7.5 mg/week, which was increased to 15 mg/week and combined with folic acid (1 mg/day) after 4 weeks. If the Disease Activity Score in 44 joints (DAS44) was >2.4 at 3 months, MTX was increased to 25 mg/week. MTX efficacy was evaluated at 3 and 6 months and compared for genotypes in 3 analyses: patients with and without good response (DAS44 <2.4), patients with and without good improvement (⌬DAS44 >1.2), and patients with and without moderate improvement (⌬DAS44 >0.6). The association between MTX-related adverse drug events (ADEs) and genotype was evaluated by comparing genotypes between patients with and without ADEs, specifically pneumonitis, gastrointestinal ADEs, skin and mucosal ADEs, and elevated liver enzyme levels. The following SNPs were analyzed: methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, dihydrofolate reductase (DHFR) ؊473G>A, DHFR 35289G>A, and reduced folate carrier 80G>A. In case of significant differences, odds ratios (ORs) were calculated.Results. At 6 months, MTHFR 1298AA was associated with good improvement relative to 1298C (OR 2.3, 95% confidence interval [95% CI] 1.18-4.41), which increased with increased copies of the MTHFR 677CC haplotype. In contrast, MTHFR 1298C allele carriers developed more ADEs (OR 2.5, 95% CI 1.32-4.72).Conclusion. Patients with MTHFR 1298AA and MTHFR 677CC showed greater clinical improvement with MTX, whereas only the MTHFR 1298C allele was associated with toxicity. In the future, MTHFR genotypes may help determine which patients will benefit most from MTX treatment.Methotrexate (MTX) is the most widely used disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA), and has proven to reduce disease activity and delay or stabilize the development of bone erosions (1,2). However, only ϳ50% of the patients experience good clinical response, and 30% discontinue therapy due to side effects (3,4).

Objectives: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis (RA). Methods: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy (group 1); step-up combination therapy (group 2); initial combination therapy with tapered high-dose prednisone (group 3); or initial combination therapy with infliximab (group 4). Results: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (20.9 and 21.6%, 20.6 and 21.4%, 21.7 and 23.3%, and 22.6 and 23.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. Conclusions: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD loss.Erosions and hand and generalised bone mineral density (BMD) loss in rheumatoid arthritis (RA) [1][2][3] results in functional disability and increased risk of clinical fractures. [4][5][6] Recent studies suggest that pathophysiological mechanisms of focal erosions and hand and generalised BMD loss have common pathways mediated by osteoclasts, in particular by the receptor activator of nuclear factor-kb ligand. [7][8][9] Clinical studies evaluating BMD in the hands and generalised BMD in the hip and spine of patients with early RA showed associations between high BMD loss and disease severity, as measured by inflammation parameters, (progressive) joint damage and functional disability. [10][11][12][13][14] In patients with RA, corticosteroids decrease generalised BMD loss by suppression of inflammatory activity, but as a side-effect, also increase BMD loss.14-19 Treatment with tumour necrosis factor a antagonist (anti-TNFa) might protect against generalised BMD loss. [20][21][22] However, little is known about the effect of corticosteroids 23 and anti-TNFa 21 on hand BMD loss. While the efficacy of calcium and vitamin D supplements remains inconclusive, use of bisphosphonates has been shown to protect against, especially corticosteroid-induced, generalised BMD loss. [24][25][26][27][28] The influence of antireso...

ABSTRACT

Dutch College of Health Insurance Companies, Schering-Plough, and Janssen.

In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.