Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis.

OBJECTIVE: There is increasing evidence that adipocytokines may exert proinflammatory and destructive effects in rheumatoid arthritis (RA). Hence, the authors investigated the relationship between adipocytokines and several features associated with RA (inflammation, joint destruction and cardiovascular disease), as well as the effect of treatment with a tumour necrosis factor inhibitor or glucocorticoids (GCs) hereupon. METHODS: Serum levels of adiponectin, leptin, resistin, visfatin, vaspin and lipids were determined in a well-defined cohort of patients with RA before and after 16 weeks of adalimumab treatment (adalimumab cohort). The same parameters were analysed in two other cohorts of patients with RA before and after 2 weeks of high-dose prednisolone (high GC cohort) and before and after 22 weeks of treatment with a combination regimen with tapered high-dose prednisolone (COBRA -GC cohort). Radiographs of hands and feet (adalimumab and COBRA-GC cohorts) were assessed at baseline and after treatment. RESULTS: Treatment with adalimumab or GC showed opposing effects on vaspin and visfatin levels. Lipid levels improved after several months of adalimumab or GC treatment; in the adalimumab cohort, this was related to reduced visfatin levels, independent of C reactive protein levels. After long-term adalimumab or GC treatment, resistin levels declined, which was associated with a decrease in inflammation markers. In the adalimumab cohort, baseline resistin levels were predictive of baseline radiological damage, independent of anticitrullinated peptide antibodies status or C reactive protein levels. CONCLUSION: Changes in serum adipocytokine levels were treatment specific, further strengthening the role of visfatin and resistin in several disease manifestations of RA.

Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimumab.

OBJECTIVES: The mechanism of action of treatment with tumour necrosis factor (TNF) blockers in rheumatoid arthritis (RA) is still not completely understood. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium. METHODS: A novel technique was used to analyse the migration of labelled autologous monocytes before and 14 days after initiation of adalimumab treatment using scintigraphy. CD14 monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labelled with technetium-99m-hexamethylpropylene-amino-oxime. Scintigraphic scans were made 1, 2 and 3 h after re-infusion. RESULTS: As early as 14 days after the start of treatment with adalimumab a significant decrease in disease activity score evaluated in 28 joints was shown. There was no significant decrease in the influx of monocytes into the joint at this time. CONCLUSIONS: This study indicates that adalimumab treatment does not reduce the influx of monocytes into the synovium early after initiation of treatment. As previous studies showed a rapid decrease in macrophage infiltration after TNF-antibody therapy, which could not be explained by increased cell death, this points to an important role for enhanced efflux of inflammatory cells from the synovium.

Work ability: a new outcome measure in rheumatoid arthritis?

OBJECTIVES: To assess the relationship between disease activity and work ability, quality of life (QoL), and fatigue in patients with RA during a 12-month course of the tumour necrosis factor (TNF)-blocking agent adalimumab. METHODS: RA patients in the working age category who started treatment with adalimumab were included consecutively and followed up for 12 months. Generalized estimating equation (GEE) analyses were used to study relationships between disease activity and the outcome variables work ability, QoL, and fatigue at baseline, 6 months, and 12 months. Disease activity was measured using the 28-joint Disease Activity Score (DAS28), quality of life was assessed with the Rheumatoid Arthritis-specific Quality of Life instrument (RAQoL), and fatigue was assessed using the Checklist Individual Strength (CIS) questionnaire and the Need for Recovery scale (NFR). RESULTS: After 1 year, markedly improvement was seen not only in the DAS28 (from 5.2 +/- 1.2 to 3.1 +/- 1.6) but also in work ability, RAQoL, and work-related fatigue, which improved by 50, 29, and 34%, respectively. At all three time points strong significant associations were observed between DAS28 and work ability, RAQoL, and work-related fatigue and this relationship remained strong after adjustment for confounders. CONCLUSIONS: Disease activity was associated with QoL, work-related fatigue, and work ability in a group of RA patients treated with adalimumab for 1 year. As improvement in these factors influences work participation positively and work ability measures more than health status, the current results suggest that simple tools such as work ability should be used more frequently as outcome measures in trials with RA patients.