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Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

ABSTRACT: Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA.Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months). Patients were categorized according to BMI: normal (BMI 18.5 to <25), overweight (BMI 25-30), and obese (BMI >30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued the TNFi were considered nonresponders. We controlled for age, sex, HLA-B27, axSpA type, BASDAI, BASMI, elevated C-reactive protein (CRP), current smoking, enthesitis, physical exercise, and co-medication with disease-modifying antirheumatic drugs, as well as with nonsteroidal anti-inflammatory drugs in multiple adjusted logistic regression analyses.A total of 624 axSpA patients starting a first TNFi were considered in the current study (332 patients of normal weight, 204 patients with overweight, and 88 obese patients). Obese individuals were older, had higher BASDAI levels, and had a more important impairment of physical function in comparison to patients of normal weight, while ASDAS and CRP levels were comparable between the three BMI groups. An ASAS40 response was reached by 44%, 34%, and 29% of patients of normal weight, overweight, and obesity, respectively (overall p?=?0.02). Significantly lower odds ratios (ORs) for achieving ASAS40 response were found in adjusted analyses in obese patients versus patients with normal BMI (OR 0.27, 95% confidence interval (CI) 0.09-0.70). The respective adjusted ASAS40 OR in overweight versus normal weight patients was 0.62 (95% CI 0.24-1.14). Comparable results were found for the other outcomes assessed.Obesity is associated with significantly lower response rates to TNFi in patients with axSpA.

SUBMITTER: Micheroli R

PROVIDER: S-EPMC5518107 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

Micheroli Raphael R Hebeisen Monika M Wildi Lukas M LM Exer Pascale P Tamborrini Giorgio G Bernhard Jürg J Möller Burkhard B Zufferey Pascal P Nissen Michael J MJ Scherer Almut A Ciurea Adrian A

Arthritis research & therapy 20170719 1

<h4>Background</h4>Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA.<h4>Methods</h4>Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment i ...[more]

PMID: 28724442

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Project description:OBJECTIVE:Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). METHODS:We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout. RESULTS:For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (? = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (? = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers ? = -0.1, 95% CI -0.5, 0.3; current smokers ? = -0.01, 95% CI -0.4, 0.4) at 3 months. CONCLUSION:TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.

Project description:Spondyloarthritis Research Consortium Canada (SPARCC) score is an effective magnetic resonance imaging (MRI) evaluation method for inflammation in axial spondyloarthritis. Previously published meta-analyses have shown tumor necrosis factor α inhibitors (TNFi) had great effectiveness on improving disease activity and function in axial spondyloarthritis. However, there still has no one that concentrates on the impact of TNFi on MRI inflammation. We conduct a meta-analysis to summarize the impact of TNFi on MRI inflammation in axial spondyloarthritis using SPARCC score. Comprehensive search was conducted in the databases of OVID Medline, OVID EMBASE, and Cochrane library on November 14, 2020. We investigated the differences in SPARCC score of sacroiliac joint and spine, before and after TNFi treatment in patients with axial spondyloarthritis. SPARCC score was further compared in the subgroup by diagnostic category and TNFi types. In addition, clinical assessment indicators including ankylosing spondylitis disease activity score, bath ankylosing spondylitis disease activity index, bath ankylosing spondylitis functional index, c-reactive protein were also analyzed. Data were pooled by mean differences (MD) with 95% confidence intervals (CI) and publication bias was assessed by Egger's test. Jadad scale was applied to assess the quality of included trials. Compared with control group, TNFi significantly improved SPARCC score of sacroiliac joints (n = 11, MD = 2.86, 95% CI 2.50, 3.23) and spine (n = 5, MD = 1.87,95%CI 1.27, 2.46). This effect was consistent among subgroups by different diagnostic category (ankylosing spondylitis, non-radiographic axial spondyloarthritis) and TNFi types (adalimumab, certolizumab pegol). Analysis of clinical assessment indicators also confirmed the therapeutic effect on axial spondyloarthritis. Egger's test suggested no possibility of publication bias. This meta-analysis shows that TNFi are effective to improve MRI inflammation in patients with axial spondyloarthritis and the treatment effectiveness is not affected by diagnostic category and TNFi types.

Project description:Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is an anti-inflammatory protein implicated in multiple autoimmune and rheumatologic conditions. We hypothesized that lower levels of TNFAIP3 contributes to excessive cytokine production in response to inflammatory stimuli in axial spondyloarthritis (AxSpA). A further aim was to determine the immune signaling and genetic variation regulating TNFAIP3 expression in individual subjects.Blood-derived macrophages from 50 AxSpA subjects and 30 healthy controls were assessed for TNFAIP3 expression. Cell lysates were also analyzed for NF-?B, mitogen-activated protein (MAP) kinase and STAT3 phosphorylation, and supernatants for cytokine production. Coding and regulatory regions in the TNFAIP3 gene and other auto-inflammation-implicated genes were sequenced by next-generation sequencing and variants identified.Mean TNFAIP3 was significantly lower in spondyloarthritis macrophages than controls (p?=?0.0085). Spondyloarthritis subject macrophages correspondingly produced more TNF-? in response to lipopolysaccharide (LPS, p?=?0.015). Subjects with the highest TNFAIP3 produced significantly less TNF-? in response to LPS (p?=?0.0023). Within AxSpA subjects, those on TNF blockers or with shorter duration of disease expressed lower levels of TNFAIP3 (p?=?0.0011 and 0.0030, respectively). TNFAIP3 expression correlated positively with phosphorylated I?B?, phosphorylated MAP kinases, and unstimulated phosphorylated STAT3, but negatively with LPS or TNF-?-stimulated fold induction of phosphorylated STAT3. Further, subjects with specific groups of variants within TNFAIP3 displayed differences in TNFAIP3 (p?=?0.03-0.004). Nominal pQTL associations with genetic variants outside TNFAIP3 were identified.Our results suggest that both immune functional and genetic variations contribute to the regulation of TNFAIP3 levels in individual subjects. Decreased expression of TNFAIP3 in AxSpA macrophages correlated with increased LPS-induced TNF-?, and thus, TNFAIP3 dysregulation may be a contributor to excessive inflammatory responses in spondyloarthritis subjects.

Dataset Information

Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

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Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

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