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Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

ABSTRACT: To identify predictors of response to tumor necrosis factor (TNF) antagonists in ankylosing spondylitis (AS) and psoriatic arthritis (PsA).Systematic review and meta-analysis of clinical trials and observational studies based on a systematic search. Meta-analyses of similar observations were performed using random effects computing summary OR. Heterogeneity was tested using I(2), and risks of bias using funnel plots and the Egger test. Meta-regression was used to explore causes of heterogeneity.The electronic search captured 1340 references and 217 abstracts. 17 additional articles were identified after searching by hand. A total of 59 articles meet the purpose of the study and were reviewed. 37 articles (33 studies) included 6736 patients with AS and 23 articles (22 studies) included 4034 patients with PsA. 1 article included data on AS and PsA. Age (OR (95% CI) 0.91 (0.84 to 0.99), I(2)=84.1%), gender (1.57 (1.10 to 2.25), I(2)=0.0%), baseline BASDAI (1.31 (1.09 to 1.57), I(2)=0.0%), baseline BASFI (0.86 (0.79 to 0.93), I(2)=24.9%), baseline dichotomous C reactive protein (CRP) (2.14 (1.71 to 2.68), I(2)=22.3%) and human leucocyte antigen B27 (HLA-B27) (1.81 (1.35 to 2.42), I(2)=0.0%) predict BASDAI50 response in AS. No factor was identified as a source of heterogeneity. Only meta-analysis of baseline BASFI showed risk of publication bias (Egger test, p=0.004). Similar results were found for ASAS criteria response. No predictors of response were identified in PsA.Young age, male sex, high baseline BASDAI, low baseline BASFI, high baseline CRP and HLA-B27 predict better response to TNF antagonists in AS but not in PsA.

SUBMITTER: Maneiro JR

PROVIDER: S-EPMC4612701 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

Maneiro Jose Ramon JR Souto Alejandro A Salgado Eva E Mera Antonio A Gomez-Reino Juan J JJ

RMD open 20150218 1

<h4>Objective</h4>To identify predictors of response to tumor necrosis factor (TNF) antagonists in ankylosing spondylitis (AS) and psoriatic arthritis (PsA).<h4>Methods</h4>Systematic review and meta-analysis of clinical trials and observational studies based on a systematic search. Meta-analyses of similar observations were performed using random effects computing summary OR. Heterogeneity was tested using I(2), and risks of bias using funnel plots and the Egger test. Meta-regression was used t ...[more]

PMID: 26509050

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Project description:To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho = -0.37 and rho = -0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.

Project description:IntroductionThis article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.MethodsThis integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).ResultsMedian treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.ConclusionRates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.Trial registrationClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Dataset Information

Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

Publications

Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

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