Biologic therapies and systemic bone loss in rheumatoid arthritis

Dimitroulas, Theodoros; Nikas, Spyros N.; Trontzas, Panagiotis; Kitas, George D.

doi:10.1016/j.autrev.2013.03.015

Cited by 74 publications

(54 citation statements)

References 104 publications

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“…51 Most of the biological drugs approved for RA treatment have proinflammatory cytokines as targets, although these agents cannot be used over long time periods. 52 It has been demonstrated that MTX induces IL-6 secretion in human cell lines. 53 However, when PBMC from RA patients were stimulated with phytohemagglutinin and treated with MTX, an increase in Th2 cytokines and a decrease in Th1 cytokines was observed.…”

Section: Discussionmentioning

confidence: 99%

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Aira

Hernández

Prada³

et al. 2015

mAbs

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(2016) Immunological evaluation of rheumatoid arthritis patients treated with itolizumab, mAbs, 8:1, 187-195, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

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Section: Discussionmentioning

confidence: 99%

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Aira

Hernández

Prada³

et al. 2015

mAbs

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“…Reviews of the effects of biologic agents and steroids on bone loss have been performed (7)(8)(9); however, these were narrative reviews or included data from observational studies as well as randomized controlled trials (RCTs), potentially introducing bias. The purpose of this systematic review was to examine the effects of antirheumatic drugs on bone loss at various sites (hand, lumbar spine, and hip) in RA, ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis, based on evidence from RCTs.…”

Section: Introductionmentioning

confidence: 99%

Meta‐Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials

Siu

Haraoui

Bissonnette

et al. 2015

Arthritis Care & Research

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Objective. To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review. Methods. Electronic databases were systematically searched for randomized controlled trials. Studies were grouped based on disease, treatment, and site of BMD measurement. Change in BMD (DBMD) from baseline to end of study was recorded. Standardized mean difference (SMD) of DBMD between treatment and controls was standardized for meta-analyses and 95% confidence intervals (95% CIs) were calculated. Results. Treatment effects on BMD were not the primary outcomes of the trials. Thirteen studies were eligible (11 RA, 2 AS, 0 PsA, and 0 psoriasis). For RA, significantly less hand bone loss was seen with tumor necrosis factor inhibitors (TNFi; SMD DBMD 0.33 [95% CI 0.13, 0.53], P 5 0.001, I 2 5 0%) and glucocorticoids (SMD DBMD 0.51 [95% CI 0.20, 0.81], P 5 0.001, I 2 5 0%). TNFi had no significant effect on lumbar spine and hip BMD. Glucocorticoids were associated with a negative effect on lumbar spine (SMD DBMD 20.30 [95% CI 20.55,20.04], P 5 0.02, I 2 5 52%), but not hip BMD. For AS, a significant increase in BMD was seen with TNFi at the lumbar spine (SMD DBMD 0.96 [95% CI 0.64, 1.27], P < 0.001, I 2 5 16%) and hip (SMD DBMD 0.38 [95% CI 0.13, 0.62], P 5 0.003, I 2 5 0%). Data were insufficient to perform meta-analyses in PsA and psoriasis or for other antirheumatic drugs. Conclusion. In RA, TNFi and glucocorticoids appeared to attenuate hand bone loss. TNFi did not impact lumbar spine and hip BMD and glucocorticoids had negative effects on lumbar spine and no effect on hip BMD. In AS, TNFi was associated with improved lumbar spine and hip BMD.

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“…The role of pro-inflammatory cytokines have been underlined in the development of osteoporosis in RA, with evidence for the efficacy of biologic therapies targeting inflammatory cytokines protecting against bone degradation [82]. Heightened local and systemic inflammation resulting from SB in RA, may therefore also contribute towards increased risk of osteoporosis in these patients.…”

Section: Bone Massmentioning

confidence: 99%

Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health

et al. 2017

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Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterised by high gradeinflammation, and associated with elevated cardiovascular risk, rheumatoid-cachexia and functional impairment. Sedentary behaviour is linked to heightened inflammation, and is highly pervasive in RA -likely as a result of compromised physical function and persistent fatigue. This high sedentarity may exacerbate the inflammatory process in RA, and hold relevance for disease-related outcomes. The aim of this narrative review is to provide an overview of the definition, measurement and health relevance of sedentary behaviour in the context of RA. Contradictions are highlighted with regards to the manner in which sedentary behaviour is operationalized, and the significance of sedentary behaviour physiology for disease-outcomes in RA is outlined. The advantages and disadvantages of sedentary behaviour measurement approaches are also discussed. Against this background, we summarise studies that have reported sedentary behaviour and its health correlates in RA, and propose directions for future research.

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Biologic therapies and systemic bone loss in rheumatoid arthritis

Cited by 74 publications

References 104 publications

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Meta‐Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials

Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health

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