Blockade of tumor necrosis factor superfamily members CD30 and OX40 abrogates disease activity in murine immune-mediated glomerulonephritis.

Abstract Background The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. Methods We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan–Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy. Results Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). Conclusions A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

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FRI0374 PLASMA LEVELS OF 14-3-3 PROTEIN, S100A8/S100A9-PROTEIN, INTERLEUKIN-6, INTERLEUKIN-18, INTERLEUKIN-4, INTERLEUKIN-17, INTERLEUKIN-1Β AND TUMOR NECROSIS FACTOR-Α IN CHRONIC NON-BACTERIAL OSTEOMYEILITIS AND NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6469 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 784.3-784

Author(s):

M. Kostik ◽

M. Makhova ◽

D. Kozlova ◽

D. Vasilyev ◽

L. Sorokina ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Plasma Levels ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Systemic Juvenile Idiopathic Arthritis ◽

Immune Mediated ◽

Factor Α ◽

Necrosis Factor

Background:Chronic non-bacterial osteomyelitis (CNO) is an immune-mediated disease associated with cytokine dysbalance.Objectives:The aim of our study was to evaluate the cytokines levels in CNO and compare to juvenile idiopathic arthritis (JIA) – disease with immune-mediated mechanism.Methods:The diagnosis of CNO made with criteria, proposed by Jansson (2007, 2009), after the exclusion of other causes of bone disease [1]. We included 42 patients with NBO, 28 patients with non-systemic juvenile idiopathic arthritis (JIA). We evaluated plasma levels of 14-3-3 protein, S100A8/S100A9-protein, interleukine-6 (IL-6), interleukine-18 (IL-18), interleukine-4 (IL-4), interleukine-17 (IL-17), interleukine-1β (IL-1 β) and tumor necrosis factor-α (TNFα) in 2 groups by the ELISA. Statistical analysis was carried out with Statistica 10.0 software. We utilized descriptive statistics (Me; IQR), Mann-Whitney tests.Results:We have found differences in the proinflammatory biomarkers between CNO, JIA. Patients with NBO had lower levels of studied cytokines, exclude14-3-3-protein, S100A8/S100A9 and interleukin-6 compare to JIA patients (table 1).Table 1.Comparison the cytokine levels between CNO, JIA NParameterNBO (n=42)JIA (n=28)pHemoglobin, g/l112 (104; 124)120 (114.5; 126.0)0.02WBC x 109/l7.9 (7.0; 10.5)8.0 (6.7; 10.0)0.86PLT x 109/l347 (259; 408)336.5 (274.0; 390.5)0.98ESR. mm/h25.0 (9.0; 46.0)8.5 (2.5; 13.0)0.013CRP, mg/l6.1 (0.6; 2.4)1.8 (0.4; 11.9)0.02714-3-3, ng/ml21.4 (18.5; 27.1)19.9 (18.0; 27.8)0.77S100A8/S100A9, ng/ml5.9 (5.2; 6.5)5.9 (5.0; 6.2)0.76IL-6, ng/ml126,2 (112.8; 137.5)132.4 (117.4; 142.9)0.16IL-18, ng/ml270.1 (200.1; 316.1)388.3 (373.9; 405.1)0.0000001IL-4, ng/ml15.3 (11.5; 18.2)18.7 (16.2; 20.2)0.003IL-17, ng/ml83.1 (71.1; 97.3)99.2 (87.3; 115.8)0.003IL-1b, ng/ml47.4 (42.0; 51.3)70.8 (65.3; 73.6)0.0000001TNFa, ng/ml19.4 (17.8; 21.3)23.1 (20.2; 25.9)0.0006Conclusion:Patients with CNO had less proinflammatory activity then JIA patients, besides IL-6 and S100A8/S100A9. Further investigations required for finding new more precise biomarkers and finding possible molecular targets for treatment.This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001)References:[1]Jansson AF, et al. Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheum. 2009;60(4):1152-9.Disclosure of Interests:None declared

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Determinants Associated with Work Participation in Patients with Established Rheumatoid Arthritis Taking Tumor Necrosis Factor Inhibitors

The Journal of Rheumatology ◽

10.3899/jrheum.130878 ◽

2014 ◽

Vol 41 (7) ◽

pp. 1263-1269 ◽

Cited By ~ 4

Author(s):

Sofie H.M. Manders ◽

Wietske Kievit ◽

Annemarie L.M.A. Braakman-Jansen ◽

Herman L.M. Brus ◽

Lidy Hendriks ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Functional Status ◽

Tumor Necrosis ◽

Work Participation ◽

P Value ◽

Retirement Pension ◽

Patient Reported ◽

Necrosis Factor

Objective.Reduced work participation (WP) is a common problem for patients with rheumatoid arthritis (RA) and generates high costs for society. Therefore, it is important to explore determinants of WP at the start of tumor necrosis factor inhibitor (TNFi) treatment, and for changes in WP after 2 years of TNFi treatment.Methods.Within the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic register, WP data were available from 508 patients with RA younger than 65 years and without an (early) retirement pension. WP was registered at start of TNFi treatment and after 2 years of followup and was measured by single patient-reported binary questions whether they had work, paid or voluntary, or had a disability allowance or a retirement pension. Determinants measured at baseline were age, sex, disease duration, functional status [through Health Assessment Questionnaire-Disability Index (HAQ-DI)], 28-joint Disease Activity Score (DAS28), rheumatoid factor, presence of erosions, number of previous disease-modifying antirheumatic drugs, and number of comorbidities. During the 2 years of followup, HAQ-DI response and European League Against Rheumatism response were measured. Univariate analyses (excluded if p value was > 0.2) and multivariate (excluded if p value was > 0.1) logistic regression analyses were used.Results.Determinants associated with WP at baseline were having a better HAQ-DI (OR 0.32, p = 0.000) and male sex (OR 0.65, p = 0.065). After 2 years of TNFi therapy, 11.8% (n = 60) started to work and 13.6% (n = 69) stopped working. Determinants associated with starting to work were better baseline HAQ-DI (OR 0.58), positive RF (OR 2.73), and young age (OR 0.96); and for stopping work, worse baseline HAQ-DI (OR 2.74), low HAQ-DI response (OR 0.31), and comorbidity (OR 2.67), all with p < 0.1.Conclusion.Young patients with RA and a high functional status without any comorbidity will have a better chance of working. This supports the main goal in the management of RA: to suppress disease activity as soon and as completely as possible to prevent irreversible destruction of the joints, and thus maintain a good functional status of the patient. Because of the low proportion of variance explained by the models in this study, other factors besides the ones studied are associated with WP.

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Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.080615 ◽

2009 ◽

Vol 36 (4) ◽

pp. 837-842 ◽

Cited By ~ 18

Author(s):

ANA FILIPA MOURÃO ◽

JOANA CAETANO-LOPES ◽

PAULA COSTA ◽

HELENA CANHÃO ◽

MARIA JOSÉ SANTOS ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Inflammatory Activity ◽

Serum Concentrations ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

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