Circulating complexes between tumour necrosis factor‐alpha and etanercept predict long‐term efficacy of etanercept in juvenile idiopathic arthritis

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders; Månsson, Bengt

doi:10.1111/apa.13319

Cited by 19 publications

(13 citation statements)

References 24 publications

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“…This was supported by recent findings that formation of complexes between TNF-a and ETN results in the accumulation of inactive TNF-a in the circulation of patients with JIA and may be associated with drug response. 46 However, the sample size of patients treated with ETN in our study was small, and a larger cohort of patients is needed to further evaluate the viability of TNF-a as a marker of ETN response.…”

Section: Discussionmentioning

confidence: 90%

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

2017

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Plasma cytokine levels were responsive to MTX therapy in patients with JIA, but only TNF-α and IL-6 levels were consistently associated with disease activity and therapeutic response. Increased TNF-α levels at baseline were associated with failure to respond to standard-dose MTX and the need for more aggressive drug therapy. Initiation of ETN resulted in increased TNF-α levels that corresponded with therapeutic response, suggesting a potential clinical benefit of monitoring TNF-α levels as a pharmacodynamic marker of etanercept activity.

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Section: Discussionmentioning

confidence: 90%

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

2017

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“…Quantification of TNF during anti-TNF treatment might provide insight in treatment efficacy and / or the role of TNF during treatment. Numerous studies have investigated TNF concentrations during anti-TNF treatment in patients (1)(2)(3)(4)(5). However, the quantification of TNF is challenging for a number of reasons.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay

et al. 2019

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Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.e., a “drug-tolerant” assay. In 193 consecutive adalimumab-treated patients with RA, we demonstrated that circulating TNF increased in average of >50-fold upon treatment and reached a stable concentration in time for most patients. A similar increase in TNF was found in 30 healthy volunteers after one dose of adalimumab. This implies that TNF in circulation during anti-TNF treatment is not primarily associated with disease activity. During treatment, TNF was in complex with adalimumab and could be recovered as inactive 3:1 adalimumab-TNF complexes. No quantitative association was found between TNF and adalimumab concentrations. Low TNF concentrations at week 4 were associated with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Also in healthy volunteers, early low TNF concentrations are associated with ADAs. In conclusion, longitudinal TNF concentrations are mostly stable during adalimumab treatment and may therefore not predict successful treatment discontinuation. However, early low TNF is strongly associated with ADA formation and may be used as timely predictor of nonresponse toward adalimumab treatment.

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“…Furthermore, in non‐sJIA patients that fail MTX and need anti‐TNF therapy, baseline MRP8/14 levels are also found to be higher in responders compared to non‐responders . After start of treatment the MRP8/14 levels decrease only in responders . Therefore, patients with low MRP8/14 levels at the start of anti‐TNF treatment might need closer monitoring of the treatment effect than the ones with higher levels.…”

Section: Biomarkers In the Other Subtypes Of Jiamentioning

confidence: 99%

“…Non‐sJIA patients with a high baseline MRP8/14 are more likely to respond favorably to the standard systemic therapy with methotrexate (MTX) . Furthermore, in non‐sJIA patients that fail MTX and need anti‐TNF therapy, baseline MRP8/14 levels are also found to be higher in responders compared to non‐responders . After start of treatment the MRP8/14 levels decrease only in responders .…”

Section: Biomarkers In the Other Subtypes Of Jiamentioning

confidence: 99%

Understanding inflammation in juvenile idiopathic arthritis: How immune biomarkers guide clinical strategies in the systemic onset subtype

2016

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The translation of basic insight in immunological mechanisms underlying inflammation into clinical practice of inflammatory diseases is still challenging. Here we describe how-through continuous dialogue between bench and bedside-immunological knowledge translates into tangible clinical use in a complex inflammatory disease, juvenile idiopathic arthritis (JIA). Systemic JIA (sJIA) is an autoinflammatory disease, leading to the very successful use of IL-1 antagonists. Further immunological studies identified new immune markers for diagnosis, prediction of complications, response to and successful withdrawal of therapy. Myeloid related protein (MRP)8, MRP14, S100A12, and Interleukin-18 are already used daily in clinic as markers for active sJIA. For non-sJIA subtypes, HLA-B27, antinuclear-antibodies, rheumatoid factor, erythrocyte sedimentation rate, and Creactive protein are still used for classification, prognosis or active disease. MRP8, MRP14, and S100A12 are now under study for clinical practice. We believe that with biomarkers, algorithms can soon be designed for the individual risk of disease, complications, damage, prediction of response to, and successful withdrawal of therapy. In that way, less time will be lost and less pain will be suffered by the patients. In this review, we describe the current status of immunological biomarkers used in diagnosis and treatment of JIA.Keywords: Biomarkers r Classification r Juvenile arthritis r Prognosis r Recurrence IntroductionJuvenile idiopathic arthritis (JIA) is the most common occurring chronic rheumatic disease in childhood with incidence rates varying from 1.6 to 23 and prevalence from 3.8 to 400 per 100 000 in the European population in 2010 [1]. JIA is a complex inflammatory disease with a multifactorial immune pathogenesis. Next to a certain genetic predisposition, environmental factors play a role leading to a chronic inflammatory response, which involves uncontrolled activation of both innate and adaptive immunities [2]. The resulting autoimmune assault targets primarily, though not excluCorrespondence: Dr. Joost F. Swart e-mail: jswart@umcutrecht.nl sively, synovial tissue, leading to chronic arthritis. The treatment for a patient with JIA nowadays still starts with low-dose or nonaggressive therapies and will only be escalated if it is failing after several months [3]. This leads to therapy failures of at least 50% in the first six months of treatment resulting in frustration, pain, and probably even damage to the treated tissue [4]. JIA patients would benefit from personalized treatment in which the individual prediction on therapy-response to certain drugs is taken into account in the choice of the anti-rheumatic therapy. As will be discussed below, over the past decade an increased understanding of the immunological mechanisms underlying JIA has led to the identification of immune biomarkers that can actually guide therapeutic strategies.Clinically, JIA therefore is defined as arthritis of unknown origin that starts before the age of 16, and persists...

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Circulating complexes between tumour necrosis factor‐alpha and etanercept predict long‐term efficacy of etanercept in juvenile idiopathic arthritis

Cited by 19 publications

References 24 publications

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay

Understanding inflammation in juvenile idiopathic arthritis: How immune biomarkers guide clinical strategies in the systemic onset subtype

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