Background Major radiographic markers for joint damage in rheumatoid arthritis (RA) are erosions and joint space narrowing (JSN). JSN may also be a manifestation of (primary) osteoarthritis becoming more prominent with age. We hypothesize that JSN progression and predictors of JSN may differ between older and younger RA patients.
Objectives To compare and identify age-specific baseline risk factors for the development of JSN in RA.
Methods 10 year follow up data of the BeSt study, a randomized controlled treat-to-target trial in early RA (1987 criteria) were used. Missing data were accounted for using multiple imputation. JSN progression was defined as ≥0.5 points progression of narrowing part of the Sharp-van der Heijde score (SHS) during 10 years. Median age at baseline was 54.9 years. Three age subgroups were created: ≥55, ≥40<55 and <40 at baseline. Separate logistic regression analysis for each group were performed, with JSN progression as binary outcome. Potential predictors with a p-value <0.2 in the univariate analysis were entered in a multivariate logistic regression.
Results Both at baseline and after 10 years, SHS and JSN were higher in the patients ≥55 and JSN was found more often (table 1). After 10 years of treatment JSN progression occurred in 167/248 (67%), 117/187 (65%) and 48/81 (59%) of the older, younger and youngest groups. Median JSN progression was (IQR; mean ± SD) 1.8 (0.0-5.5; 5.4±1.8), 1.9 (0.0-7.5; 6.2±11.2) and 1.0 (0.0-5.0; 8.2±19.3) (p=0.352), respectively.
Univariate analysis showed that in the older subgroup, smoking (OR 2.46 (95% CI 1.22-4.96)) and the combined presence of rheumatoid factor and anti-citrullinated protein antibodies (RF+ ACPA+) (3.92 (1.82-8.42)) were associated with JSN progression. In the younger subgroup, baseline total swollen joint count (SJC) (0.94 (0.90-0.99)), ESR (1.02 (1.00-1.03)), and disease activity score (DAS) (3.67 (1.07-12.65)), and RF+ ACPA+ (4.68 (2.03-10.78)) were associated. In the group <40, none of the potential risk factors were significantly associated. All potential risk factors with p<0.2 (C-reactive protein (1.02 (1.00-1.03)) and swollen joint count (1.07 (0.98-1.18))) were entered in the multivariate analysis.
In the multivariate regression, in the older subgroup smoking (2.21 (1.01-4.84)) and RF+ ACPA+ (3.25 (1.44-7.30)) were significantly associated with JSN progression. In the younger subgroup, smoking was not associated, but RF+ ACPA+ (3.01 (1.21-7.48)) was. In the group <40 none of the potential risk factors were significantly associated, possibly due to small group size.
Conclusions At baseline, RA patients ≥55 years show more often and more JSN. After 10 years of treat-to-target DAS≤2.4 these patients don't show more progression than patients aged <55. RF+ ACPA+ is a risk factor for JSN progression in patients ≥40. In patients ≥55 smoking also presents a risk. In patients between 40 and 55 years, RF+ ACPA+, high ESR, low SJC and high DAS were associated with JSN progression. This suggests that JSN progression is related to (residual) rheumatoid inflammation, but in older patients may also represent occurrence of osteoarthritis.
Disclosure of Interest X. Matthijssen: None declared, G. Akdemir: None declared, I. Markusse: None declared, H. Ronday: None declared, K. Han: None declared, J. van Groenendael: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, C. Allaart Grant/research support from: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.