Predictors of joint damage in patients with early rheumatoid arthritis treated with high‐dose methotrexate with or without concomitant infliximab: Results from the ASPIRE trial

Abstract

Objective. To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX.Methods. Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54.Results. C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (>3 mg/dl) and ESR (>52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS >10.5) showed less progression with infliximab plus MTX compared with MTX alone (؊0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab.Conclusion. High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiv-

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…In general, the reduction in CRP and ESR levels correlate with a decrease in clinical disease activity (32) and less joint destruction (33), although this may be due, in part, to the direct systemic effect of TNFi on hepatic synthesis of acute-phase proteins rather than a true improvement in local synovitis. In fact, CRP level is an important biomarker of radiographic progression in RA patients receiving DMARDs (methotrexate), but this predictive value disappears when RA patients are treated with TNFi (34). Moreover, calprotectin serum levels significantly decrease after TNFi treatment and are independently associated with radiographic progression in RA (14,17).…”

Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti–tumor necrosis factor therapy in rheumatoid arthritis

“…The present study demonstrated that a simple cortisol and ACTH measurement can help to further guide anti-TNF antibody treatment. This is particularly relevant because important parameters such as CRP level, ESR, and swollen joint count are not predictive in RA patients treated with anti-TNF antibodies plus methotrexate (18). We suggest that inclusion of cortisol and ACTH and their respective molar ratio in the decision-making process can help to determine the appropriateness of anti-TNF therapy in patients with RA.…”

TNFα blockade in human diseases: An overview of efficacy and safety

“…Subsequent clinical trials evaluated whether the combination of a DMARD and an anti-TNFα agent was superior to either agent alone [11,12] or compared an anti-TNF agent with placebo [13,14]. Emboldened by the positive results of these trials, investigators probed a window of opportunity by asking whether treating patients with an anti-TNF agent in early stages (less than 3 years) of disease could 'wipe out' the disease and provide long-lasting remissions [12,[15][16][17].…”