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Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.

ABSTRACT: Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNF? Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA?+?MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA?+?MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.Clinicaltrials.gov NCT00195663. Registered 13 September 2005.

SUBMITTER: Landewe R

PROVIDER: S-EPMC4440309 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.

Landewé Robert R Smolen Josef S JS Florentinus Stefan S Chen Su S Guérette Benoît B van der Heijde Désirée D

Arthritis research & therapy 20150521

<h4>Introduction</h4>Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.<h4>Methods</h4>The Prospective Mul ...[more]

PMID: 25994819

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Project description:ObjectiveMusculoskeletal ultrasound real-time image acquisition and scoring are complex, and many factors affect reliability. Static image reliability does not guarantee real-time scoring. This study aimed to identify factors and solutions to improve real-time scoring reliability for the grey scale and power Doppler evaluation of synovitis. We also report on using a novel musculoskeletal ultrasound synovitis rule-based scoring atlas.MethodsIn four stages, we evaluated inter- and intra-reader reliability among three ultrasonographers (US1-3). Intra- and inter-reader reliability was calculated using weighted-kappa, intraclass correlation coefficient, and Spearman correlation. Reliability statistics were compared between stages using permutation tests to compute empirical distributions for differences in those statistics. At each stage, factors that diminished reliability were identified and addressed. After intensive reliability exercises, a RA MSUS atlas with in-depth scoring rules was generated to improve interpretive reliability.ResultsThe three ultrasonographers had good to excellent intra-reader reliability for real-time acquisition scoring over 2432 views (weighted kappa 0.52-0.80, intraclass correlation coefficient 0.59-0.86, and Spearman correlation 0.64-0.86). Inter-reader reliability was good to excellent between US1/US2 and US1/US3 (weighted kappa 0.51-0.66, intraclass correlation coefficient 0.66-0.75, Spearman correlation 0.59-0.73). US1 achieved significant improvement in intra-reader reliability from stage 1 to stage 2 (p<0.05, weighted-kappa 0.63 to 0.80, intraclass correlation coefficient 0.71 to 0.86, Spearman 0.67 to 0.86) with use of the atlas. Conclusion: This rheumatoid arthritis musculoskeletal ultrasound study addressed complex factors affecting musculoskeletal ultrasound acquisition-scoring reliability. Systematic identification and amelioration of many factors and using a novel rule-based scoring atlas significantly improved intra-reader reliability.

Project description:BackgroundAnti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment; however, a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating T helper 17 (Th17) cells, but the relationship to treatment response is unclear. To identify immune correlates of anti-TNF treatment response, we conducted a longitudinal study using clinical, ultrasound and T cell assessments.MethodsPatients with RA (n = 25) were studied at protocol visits during the initial 12 weeks of anti-TNF treatment. Improvement in the disease activity score of 28 joints (DAS28) >1.2 defined treatment responders (n = 16) and non-responders (n = 9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by grey scale and power Doppler ultrasound. The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).ResultsThe frequency of circulating IL17-producing cells increased significantly 12 weeks after anti-TNF initiation (Elispot median (range) specific spot forming cells (spSFC)/106 360 (280-645) vs 632 (367 - 1167), p = 0.003). The increase in CD4 + IL17+ cells at 12 weeks was confirmed by FACS (median (range) %, 0.7 (0.5-0.9) vs 1.05 (0.6-1.3); p = 0.01). The increase in circulating Th17 cells inversely correlated with reduction in synovial vascularity (r = -0.68, p = 0.007) and thickening (r = -0.39; p = 0.04). Higher frequencies of circulating Th17 cells at baseline were associated with poorer anti-TNF treatment response defined by ultrasonographic measures.ConclusionsThese results demonstrate a link between changes in circulating Th17 cells with resolution of ultrasonographic features of synovial inflammation and vascularity during anti-TNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints or TNF-driven regulation of Th17 cell production.Trial registrationClinicalTrials.gov: NCT01060098 . Registered 29 January 2010.

Dataset Information

Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.

Publications

Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.

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