Objective:To explore the effects of anti-tumour necrosis factor (TNF)α antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA).Methods:A total of 50 patients with active RA (DAS28⩾3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (⩽10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment.Results:Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (−0.7%), (p = 0.015).Conclusion:In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects.
Objective. Oxidative stress contributes to the inflammatory properties of rheumatoid arthritis (RA) synovial T lymphocytes. This study was undertaken to investigate the mechanisms leading to production of reactive oxygen species (ROS) and oxidative stress in RA synovial T lymphocytes.Methods. ROS production in T lymphocytes from the peripheral blood (PB) of healthy donors and from the PB and synovial fluid (SF) of RA patients was measured by ROS-dependent fluorescence of 6-carboxy-2 ,7 -dichlorofluorescein. Rap1 GTPase activation was assessed by activation-specific probe precipitation. Proliferation of RA PB and SF T lymphocytes was assayed by 3 H-thymidine incorporation. In some experiments, RA PB T cells were preincubated with autologous SF or with PB or SF adherent cells. Experiments were performed in the absence or presence of transwell membranes or CTLA-4Ig fusion proteins. Short-and longterm stimulations of healthy donor PB T lymphocytes were performed with inflammatory cytokines, in the absence or presence of activating anti-CD28 antibodies. Conclusion. Cell-cell contact between T cells and RA synovial adherent cells mediates Rap1 inactivation and subsequent ROS production in T lymphocytes following exposure to inflammatory cytokines. This process can be blocked by CTLA4-Ig fusion protein.
Results. T lymphocyte ROS production and
In this short-term exploratory evaluation, a 6-month course of TNF inhibitors improved work ability and quality of life, and reduced fatigue in patients with established RA. These effects are associated with an increase in total healthcare costs, attributable to the costs of TNF inhibitors. Randomized controlled trials with a longer follow-up are needed to show a long-term effect on work disability and the potential cost-effectiveness of TNF inhibitors.
Background
Biological therapy has dramatically improved the treatment of rheumatoid arthritis (RA). One-third of patients however show a lack of clinical response to this treatment. The use of robust predictive markers of response to identify individuals who are likely to respond to biological treatments may provide guidance in optimizing treatment strategies and lead to lower costs.
Objectives
To test the ability of MRP8/14 serum complexes, a major granulocyte and monocyte protein associated with inflammation in patients with RA1, to differentiate between responders and non-responders to various biological treatments and to monitor disease activity in these RA patients.
Methods
170 RA patients were treated with adalimumab, infliximab or rituximab and were categorized into responders (n= 123) and non-responders (n = 47) according to the European League Against Rheumatism (EULAR) response criteria. Serum concentrations of MRP8/14 complexes were measured at baseline, week 4 and week 16 and divided in low and high MRP8/14 serum complexes level groups based on the median level for each treatment group. Non-parametric tests were used to analyse the data.
Results
Before initiation of adalimumab, infliximab or rituximab treatment, responders showed significantly higher levels of MRP8/14 serum complexes compared to non-responders. (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis showed that having a high level of MRP8/14 serum complexes at baseline increased the odds of being a responder by a factor of 3.3 till 55. MRP8/14 serum complexes levels decreased after 4 weeks with respectively 46% and 60% (respectively median delta changes Δ400;IQ 160-895 and 840;IQ170-1170) and 16 weeks with 61% and 68% (Δ730;IQ220-1120 and Δ970;IQ530-1830) of treatment in responders to adalimumab and infliximab, while MRP8/14 serum complexes levels were stable in non-responders. In patients treated with rituximab, MRP8/14 serum complexes decreased with 61% (Δ1670;IQ959.5-3520) after 16 weeks in responders (p = 0.0005) and increased with 89% (Δ960;IQ405-1135) after 16 weeks in non-responders to treatment (p = 0.0039).
Conclusions
MRP8/14 serum complexes can be used as a biomarker predictive of the response to biological therapy in RA patients.
References
Chen YS, Yan W, Geczy CL, Brown MA, Thomas R. Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis. Arthritis Res Ther 2009;11:R39.
Disclosure of Interest
None Declared
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.