Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids

Abstract

The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.

Abatacept Plus Methotrexate Provides Incremental Clinical Benefits Versus Methotrexate Alone in Methotrexate-naive Patients with Early Rheumatoid Arthritis Who Achieve Radiographic Nonprogression

“…The demonstration that only a portion of radiographic nonprogressors achieved clinical remission is consistent with the previously described dissociation between clinical and radiographic outcomes in patients treated with biologics or conventional DMARD 20,21,35,36 . Previous studies of combination therapy with TNF inhibitors and MTX in MTX-naive patients with early RA have shown a higher proportion of patients achieving radiographic nonprogression than those achieving clinical remission 20,21,35,36 .…”

“…Previous studies of combination therapy with TNF inhibitors and MTX in MTX-naive patients with early RA have shown a higher proportion of patients achieving radiographic nonprogression than those achieving clinical remission 20,21,35,36 . This implies that it is more difficult to achieve clinical remission than radiographic nonprogression, even with intensive early treatment with biologics.…”

Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis and Behcet's Disease

“…Positivity of RF, anti-CCP antibody and SE, disease duration and female gender are known as important predictors of radiographic progression in RA (Sanmarti et al 2007). In our study, modifi ed Larsen score of female gender was higher than that of male gender in both anti-CCP antibody-positive and -negative subgroups.…”

“…In several studies the diagnostic value of anti-CPP antibodies has been assessed and confi rmated that they are an indicator or predictor of the prognosis in RA (Lee and Schur 2003;Sanmarti et al 2007). However, as genetic differences and environmental factors may alter the anti-CCP antibody positivity (van Gaalen et al 2004;Furuya et al 2007;Kokkonen et al 2007;Verpoort et al 2007), the aims of the present study were directed to evaluate the frequency of anti-CCP antibody positivity in Turkish patients Stored sera were tested for anti-CCP antibodies by ELISA using a second-generation commercial assay kit (Euroimmun, Lubeck, Germany).…”

The Role of miRNA in Rheumatoid Arthritis

“…Once a diagnosis is established, some biomarkers provide prognostic information regarding disease progression and severity. For example, the combination of anti-CCP antibody positivity and the presence of the shared epitope defines a subset of patients with a severe form of RA (Kaltenhauser et al, 2007;Sanmarti et al, 2007), whereas the presence of specific autoantibodies define distinct subsets of inflammatory myopathies (Gunawardena et al, 2009). Other biomarkers are used to monitor the degree of immunologic activity or inflammation.…”