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OBJECTIVE: Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years. METHODS: We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985-1990, 1990-1995, 1995-2000, 2000-2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts. RESULTS: The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease-modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy. CONCLUSION: The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response., Methods: We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation., Results: We detected a statistically significant association between Δ SJC and the RA score at the CD40 locus (p=0.0004) and an inverse association between Δ SJC and the score for expression of CD39 on CD4 T cells (p=0.00005). A previously reported association between CD39 expression on regulatory T cells and response to methotrexate was in the opposite direction. In stratified analysis by concomitant methotrexate treatment, the inverse association was stronger in the combination therapy group and dissipated in the TNFi monotherapy group. Overall, ability to predict TNFi response from genotypic scores was limited, with models explaining less than 1% of phenotypic variance., Conclusions: The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and CD40 pathways could be relevant for targeting drug therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)