Predictive factors for effective selection of Interleukin-6 inhibitor and tumor necrosis factor inhibitor in the treatment of rheumatoid arthritis

Hayashi, Shinya; Matsubara, Tsukasa; Fukuda, Katsunori; Funahashi, Koji; Hashimoto, Marowa; Maeda, Toshihisa; Kamenaga, Tomoyuki; Takashima, Yoshinori; Matsumoto, Tomoyuki; Niikura, Takahiro; Kuroda, Ryosuke

doi:10.1038/s41598-020-73968-3

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…In addition, the TNF-α signalization blockade has also been done by inhibiting the TNF-α binding to its receptor through etanercept, a fully human soluble TNF receptor Fc fusion protein, where a dimer of the extracellular domains of human TNFR2 is fused to the Fc portion of human IgG1. The effectiveness of this drug has been established for the early administration from diagnosis of RA [57,58]. A phase IV study recently assessed the real-world safety and effectiveness of biosimilar etanercept in patients with RA, ankylosing spondylitis or psoriatic arthritis and receiving biosimilar etanercept injections, either 25 mg twice weekly or 50 mg once weekly [59].…”

Section: Anti-il-1β and -Tnf-α Therapies: Effects And Side Effects Of The Conventional Allopathic Dosesmentioning

confidence: 99%

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

Jacques¹,

Floris²,

Lejeune³

2021

IJMS

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Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA). Significant advances in the treatment of this pathology have been made over the past ten years, partially through the development of anti-TNF and anti-IL-1 therapies. However, major side effects still persist and new alternative therapies should be considered. The formulation of the micro-immunotherapy medicine (MIM) 2LARTH® uses ultra-low doses (ULD) of TNF-α, IL-1β, and IL-2, in association with other immune factors, to gently restore the body’s homeostasis. The first part of this review aims at delineating the pivotal roles played by IL-1β and TNF-α in RA physiopathology, leading to the development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an emphasis will be made on explaining the rationale of using multiple therapeutic targets, including both IL-1β and TNF-α in 2LARTH® medicine. Particular attention will be paid to the ULD of those two main pro-inflammatory factors in order to counteract their overexpression through the lens of their molecular implication in RA pathogenesis.

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Section: Anti-il-1β and -Tnf-α Therapies: Effects And Side Effects Of The Conventional Allopathic Dosesmentioning

confidence: 99%

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

Jacques¹,

Floris²,

Lejeune³

2021

IJMS

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“…10 Hayashi S, et al, investigated biomarkers that help in selection of RA patients suitable for treatment with tocilizumab or etanercept and found that CRP, among other factors, positively correlated with improvement in clinical outcomes making it a suitable biomarker which helps the choice of patients for such therapy. 11 CRP/albumin ration (CAR) was studied by Sunar I, et al, who demonstrated that CAR was weakly associated with RA disease activity. 12 Furthermore, CAR was also reported by He Y et al, to be significantly increased in RA patients (p<0.01) and positively correlated with CRP (Spearman's correlation = 0.99) suggesting that it could be used as an indicator of RA inflammation.…”

Section: Resultsmentioning

confidence: 99%

“…10 In another study, CRP has also been found to be a useful prognostic marker for response to tocilizumab treatment. 11 However, this study was limited as 196 patients were divided into 4 smaller subgroups limiting its statistical power. CAR was shown to be correlated with disease activity.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

Abdelhafiz¹,

Baker²,

galscow³

2021

Preprint

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Background Rheumatoid Arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. Aim To systematically explore the role of the biomarkers: C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. Methods A systematic review of the English literature using four different databases was carried out. Results CRP>7.1 mg/L predicted poor conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity, but was associated with increased radiographic damage (r=0.46, p=0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. 14-3-3η significantly correlated with inflammation, bone remodelling and osteoporosis in RA patients (p<0.05). 14 3 3η positively correlated with RA duration (p=0.003), disease activity and positive RF (P=0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity, after 6 and 12 weeks of treatment (p<0.05). MBDA score was able to differentiate between small differences in disease activity and predicted remission over one year period. Conclusion The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area.

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“…This cytokine plays a critical role in both the pathogenesis of active RA as well as the secretion of hepcidin from hepatocytes. 28,29 Due to its actual release from muscle cells (myonectin), the value of ERFE in human diseases is not restricted to anemia. In addition to being elevated in β-thalassemia major patients and associated with iron overload, 30,31 it has also been studied in CKD where EPO is the main treatment modality.…”

Section: Discussionmentioning

confidence: 99%

“…This cytokine plays a critical role in both the pathogenesis of active RA as well as the secretion of hepcidin from hepatocytes. 28 , 29 …”

Section: Discussionmentioning

confidence: 99%

Erythroferrone Expression in Anemic Rheumatoid Arthritis Patients: Is It Disordered Iron Trafficking or Disease Activity?

Youssef

Hassan²,

Morad

et al. 2021

JIR

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Purpose: Erythroferrone (ERFE) is well acknowledged for its inhibitory function on hepcidin synthesis in the liver during stress erythropoiesis, thereby ensuring sufficient iron supply to bone marrow erythroblasts. Hepcidin plays an indispensable role in the pathogenesis of anemia of chronic disease (ACD). Thus, ERFE was suggested to protect against ACD in various diseases. Rheumatoid arthritis (RA) is commonly involved with ACD and high hepcidin levels, with a further increase of the latter in active states. The present study is a case-control study that aimed to determine the pattern of ERFE expression in RA patients with concomitant ACD and study its relationship with hepcidin, erythropoietin (EPO) and disease activity. Patients and Methods: Fifty-five RA patients with ACD were categorized into active and inactive RA using the disease activity score (DAS28); 15 healthy subjects were included as control subjects. ERFE was measured for patients and control subjects using quantitative real-time polymerase chain reaction, in addition to testing for CBC, ESR, CRP, iron profile parameters and hepcidin. EPO was assessed for patients of both active and inactive RA groups. Results: ERFE and hepcidin showed the highest levels in active RA; ERFE values were similar in control subjects and inactive RA patients, while hepcidin was significantly higher in inactive RA than control subjects. Patients with high ERFE levels had higher RBC, Hct, MCV, hepcidin and EPO levels. Stepwise regression analysis has identified DAS28 and disease duration as the best predictors of ERFE values, whereas ERFE and hepcidin were independent predictors of disease activity. Conclusion:We introduce ERFE as a novel marker of RA activity. Although the inhibitory effect of ERFE on hepcidin is not evident, our results still indicate that ERFE may have a beneficial erythropoietic effect in the context of ACD in RA disease activity.

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Predictive factors for effective selection of Interleukin-6 inhibitor and tumor necrosis factor inhibitor in the treatment of rheumatoid arthritis

Cited by 6 publications

References 44 publications

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

Erythroferrone Expression in Anemic Rheumatoid Arthritis Patients: Is It Disordered Iron Trafficking or Disease Activity?

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