Therapeutic drug monitoring of infliximab in spondyloarthritis. A review of the literature

Lozano, María José Fobelo; Giménez, Reyes Serrano; Sánchez-Fidalgo, Susana

doi:10.1111/bcp.14062

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Immune cells (e.g., Th17 cells) and proinflammatory cytokines (e.g., IL-6, IL-17, and IL-1β) are important in the pathogenesis of AS ( 19 ). The inhibition of tumor necrosis factor-alpha (TNF-α) can relieve the symptoms of AS ( 20 – 22 ). The pathogenesis of AS is influenced by environmental factors including sex, age, smoking, infection, toxins, and pollutants ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Ezetimibe ameliorates clinical symptoms in a mouse model of ankylosing spondylitis associated with suppression of Th17 differentiation

Moon

Lee²,

Na³

et al. 2022

Front. Immunol.

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Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes spinal inflammation and fusion. Although the cause of AS is unknown, genetic factors (e.g., HLA-B27) and environmental factors (e.g., sex, age, and infection) increase the risk of AS. Current treatments for AS are to improve symptoms and suppress disease progression. There is no way to completely cure it. High blood cholesterol and lipid levels aggravate the symptoms of autoimmune diseases. We applied hyperlipidemia drugs ezetimibe and rosuvastatin to AS mice and to PBMCs from AS patients. Ezetimibe and rosuvastatin was administered for 11 weeks to AS model mice on the SKG background. Then, the tissues and cells of mice were performed using flow cytometry, computed tomography, immunohistochemistry, and immunofluorescence. Also, the normal mouse splenocytes were cultured in Th17 differentiation conditions for in vitro analysis such as flow cytometry, ELISA and RNA sequencing. The 10 AS patients’ PBMCs were treated with ezetimibe and rosuvastatin. The patients’ PBMC were analyzed by flow cytometry and ELISA for investigation of immune cell type modification. Ezetimibe caused substantial inhibition for AS. The present study showed that ezetimibe inhibits Th17 cell function, thereby slowing the progression of AS. It is well known that statins are more effective in reducing blood lipid concentrations than ezetimibe, however, our results that ezetimibe had a better anti-inflammatory effect than rosuvastatin in AS. This data suggests that ezetimibe has an independent anti-inflammatory effect independent of blood lipid reduction. To investigate whether ezetimibe has its anti-inflammatory effect through which signaling pathway, various in vitro experiments and RNA sequencing have proceeded. Here, this study suggests that ezetimibe can be an effective treatment for AS patients by inhibiting Th17 differentiation-related genes such as IL-23R and IL-1R. Thus, this study suggests that ezetimibe has therapeutic potential for AS through inhibition of Th17 differentiation and the production of pro-inflammatory cytokines.

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Section: Introductionmentioning

confidence: 99%

Ezetimibe ameliorates clinical symptoms in a mouse model of ankylosing spondylitis associated with suppression of Th17 differentiation

Moon

Lee²,

Na³

et al. 2022

Front. Immunol.

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Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis

Martínez‐Feito

Navarro-Compán

Hernández-Breijo

et al. 2021

Scandinavian Journal of Rheumatology

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Background: The aim of our study is to evaluate whether serum in iximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA).Methods: Longitudinal observational study involving 81 patients with axSpA recruited from the SpA-Paz cohort and monitored during in iximab therapy. Serum ITL were measured at baseline, week 2 (W2), W6 and W12 of treatment. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W54, and every 6 months thereafter until therapy failure. Nonclinically important improvement was de ned by ΔASDAS<1.1. The association between serum ITL levels at W12 and clinical outcomes (non-improvement at W52, drug survival and drop-out due to secondary ine cacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL.Results: Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/ml vs 7.1(4.3-11.3)µg/ml, respectively; p=0.007). A cut-off of ITL<6.7µg/mL at W12 was signi cantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3-3.9); ii) shorter drug survival (5.0 years (95% CI: 3.8-6.2) vs 7.6 years (95% CI: 4.8-6.9); p=0.04); and iii) higher drop-out rates due to secondary ine cacy (OR: 3.5; 95%CI: 1.2-10.2).Conclusions: Serum ITL<6.7 µg/mL at W12 were associated with long-term clinical failure in patients with axSpA, especially due to secondary ine cacy.

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Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review

et al. 2022

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Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.

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Therapeutic drug monitoring of infliximab in spondyloarthritis. A review of the literature

Cited by 3 publications

References 46 publications

Ezetimibe ameliorates clinical symptoms in a mouse model of ankylosing spondylitis associated with suppression of Th17 differentiation

Ezetimibe ameliorates clinical symptoms in a mouse model of ankylosing spondylitis associated with suppression of Th17 differentiation

Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis

Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review

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