Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNF antagonists

González‐Álvaro, Isidoro; Ortiz, Ana M.; Tomero, Eva; Balsa, Alejandro; Orte, Javier; Laffón, A; García‐Vicuña, Rosario

doi:10.1136/ard.2007.071910

Cited by 53 publications

(41 citation statements)

References 14 publications

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“…Further research showed that 35 consecutive patients with RA with low serum COMP levels had improved clinical responses to adalimumab 61. Moreover, 75 patients with longstanding RA treated with adalimumab or infliximab who achieved remission (DAS28 <2.6) had lower receptor activator for nuclear factor-κB ligand (RANKL) and RANKL:osteoprotegerin ratio at baseline 62. The balance between osteoprotegerin and RANKL is a fundamental factor in controlling bone resorption and can be influenced by several hormones and cytokines, including TNF.…”

Section: Protein Biomarkersmentioning

confidence: 99%

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response

Emery

Dörner

2011

Annals of the Rheumatic Diseases

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Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.

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Section: Protein Biomarkersmentioning

confidence: 99%

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response

Emery

Dörner

2011

Annals of the Rheumatic Diseases

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“…b Number of RANKL-positive neutrophils (%) in joint extracts from healthy and CIOA mice. Data represent mean ± SD of 6 mice/group and were obtained within Ly-6/CD11b-positive neutrophils; Student's t-test; *P \ 0.05, **P \ 0.01, ***P \ 0.001 therapy [26]. In OA patients, serum concentrations of sRANKL correlated significantly with sRANKL level in the synovial fluid, while for OPG such relation has not been found [27].…”

Section: Discussionmentioning

confidence: 94%

“…Collagenase-induced osteoarthritis (CIOA) Experimental model of OA was induced according the method of Blom et al [26]. Mice received two intraarticular injections (i.a.)…”

Section: Methodsmentioning

confidence: 99%

Involvement of soluble receptor activator of nuclear factor-κB ligand (sRANKL) in collagenase-induced murine osteoarthritis and human osteoarthritis

Dimitrova¹,

Toncheva²,

Gyurkovska³

et al. 2011

Rheumatol Int

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Joint destruction and excessive bone formation are associated with high expression of soluble receptor activator of nuclear factor-κB ligand (sRANKL). This study was undertaken to investigate the role of sRANKL in collagenase-induced osteoarthritis (CIOA) in mice and in patients with osteoarthritis (OA). The initial phase of CIOA was associated with severe proteoglycan depletion, decreased collagen density, and up-regulation of bone morphogenetic protein (BMP)-2. At the late stage of CIOA, bone remodeling was related with increased BMP2 and RANKL expression in the joints, high sRANKL, and decreased number of activated neutrophils in synovium. CIOA mice showed elevated plasma level of sRANKL but low RANKL expression on blood neutrophils. The percentage of RANKL-positive blood neutrophils was higher in patients with OA than in healthy individuals. Our data indicate that increased local and systemic levels of soluble RANKL might be indicative for OA disorders in mouse and human.

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“…Mathematical models have been extensively and successfully used in different medical field to predict clinical response to different drugs [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α blockers therapy in rheumatoid arthritis

et al. 2010

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Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.

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Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNF antagonists

Abstract: These data suggest that in patients receiving a-TNF treatment, lower serum levels of RANKL and RANKL/OPG ratio may serve to predict remission.

Cited by 53 publications

References 14 publications

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response

Involvement of soluble receptor activator of nuclear factor-κB ligand (sRANKL) in collagenase-induced murine osteoarthritis and human osteoarthritis

A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α blockers therapy in rheumatoid arthritis

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