Careram (iguratimod) / Fujifilm Holdings, Eisai, R-Pharm - LARVOL DELTA

Refluxing Mature Compost to Replace Bulking Agents: A Low-Cost Solution for Suppressing Antibiotic Resistance Genes Rebound in Sewage Sludge Composting. (PubMed, Environ Res) - "Furthermore, MR reduced 97.36% of total MGEs including Tn916/1545, IS613, Tp614 and intI3, which alleviated ARGs horizontal transfer. Overall finding proposed mature compost reflux as bulking agent was a simple method to suppress ARGs rebound and horizontal transfer, improve ARGs removal and reduce composting plant cost."

Journal

Department-specific patterns of bacterial communities and antibiotic resistance in hospital indoor environments. (PubMed, Appl Microbiol Biotechnol) - "• The gynecology department emerged as a crucial source of bacteria, ARGs and MGEs within the hospital. Additionally, it was found to exhibit a significant correlation between bacterial communities and the presence of ARGs and MGEs."

Journal • Gene Therapies • Gynecology • Ophthalmology • Otorhinolaryngology

Iguratimod Alleviates Experimental Sjögren's Syndrome by Inhibiting NLRP3 Inflammasome Activation. (PubMed, Cell Biochem Biophys) - "In vitro, results corroborated that T-614 could protect HSG cells from IFN-α-induced cell apoptosis and inflammation by inhibiting NLRP3 inflammasome activation. Our results expounded that T-614 alleviated ESS by inhibiting NLRP3 inflammasome activation."

Journal • Immunology • Inflammation • Sjogren's Syndrome • IFNA1 • NLRP3

Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose. (PubMed, Mol Med) - "T-614 is an allosteric inhibitor of MIF that prevented death and decreased hepatic hydrogen peroxide concentrations when given prophylactically in a murine model of acetaminophen overdose. Further studies are needed to elucidate the mechanistic role of MIF in APAP toxicity."

Journal • Preclinical • Hepatology • Inflammation • Liver Failure • MIF

Prevalence of antibiotics, antibiotic resistance genes, and their associations in municipal wastewater treatment plants along the Yangtze River basin, China. (PubMed, Environ Pollut) - "Amoxicillin (AMO), ofloxacin (OFL), and pefloxacin (PEF) were predominant in influents, while AMO exhibited dominance with the highest concentration of 1409 ng/L in effluents...Remarkably, ecological risk assessment revealed high risks associated with AMO and ciprofloxacin (CIP) and medium risks linked to several antibiotics, notably including OFL, roxithromycin (ROX), clarithromycin (CLA), and tetracycline (TC)...Many antibiotics displayed lower correlations with corresponding ARGs, but exhibited higher correlations with other ARGs, suggesting complex selective pressures influencing ARG propagation. Overall, the incomplete elimination of antibiotics and ARGs in WWTPs is likely to pose adverse impacts on aquatic ecosystems in the Yangtze River Basin."

Journal

Transfer and accumulation of antibiotic resistance genes and bacterial pathogens in the mice gut due to consumption of organic foods. (PubMed, Sci Total Environ) - "A total of 8 types of major ARGs and 10 mobile genetic elements (MGEs) were detected in mice gut, including tetracycline, multidrug, sulfonamide, aminoglycoside, beta-lactamase, chloramphenicol, MLSB and vancomycin resistance genes...Importantly, feeding organic food increased the relative abundance of the potentially antibiotic-resistant pathogens, Bacteroides and Streptococcus. Our results confirm that there is an increasing risk of ARGs and ARB in the gut microbiome, which highlights the importance of organic food industries taking into account the potential accumulation and transmission of ARGs as a risk factor."

Journal • Preclinical • Gene Therapies

The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: Qilu Hospital of Shandong University | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jul 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment (clinicaltrials.gov) - P4 | N=400 | Completed | Sponsor: Qilu Hospital of Shandong University | Active, not recruiting ➔ Completed | N=200 ➔ 400 | Trial completion date: Dec 2025 ➔ Oct 2023 | Trial primary completion date: Dec 2025 ➔ Sep 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Characteristics and driving factors of antibiotic resistance genes in aquaculture products from freshwater ponds in China Yangtze River Delta. (PubMed, Environ Technol) - "MGEs, mostly int1, were more effective than bacteria in increasing the ARG abundance. This study could provide a better understanding of the transmission of ARGs in the aquaculture environment and improve the quality of aquaculture products and the ecology."

Journal • Gene Therapies

The Clinical Efficacy of Immunomodulators in RA Patients (clinicaltrials.gov) - P4 | N=400 | Recruiting | Sponsor: Qilu Hospital of Shandong University

New P4 trial • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment (clinicaltrials.gov) - P4 | N=200 | Active, not recruiting | Sponsor: Qilu Hospital of Shandong University | Trial completion date: Dec 2021 ➔ Dec 2025 | Trial primary completion date: Dec 2021 ➔ Dec 2025

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Removal of antibiotic resistance genes and mobile genetic elements in a three-stage pig manure management system: The implications of microbial community structure. (PubMed, J Environ Manage) - "The results elucidated the crucial roles of the related bacterial and fungal communities in the removal of ARGs/MGEs. The compound microbial agent assisted the temperature rise of composting, thereby changing the related microbial community structure and resulting in ARGs/MGEs removal."

Journal

Nano-AlO particles affect gut microbiome and resistome in an in vitro simulator of the human colon microbial ecosystem. (PubMed, J Hazard Mater) - "This is attributed to that low concentration of nano-AlO can promote horizontal transfer of ARGs by increasing cell membrane permeability and relative abundance of transposase (e.g. tnpA, IS613, and Tp614). Our findings confirmed the adverse effects of nano-AlO on the human gut resistome and emphasized the necessity to assess potential risks of nanomaterials on the human gut health."

Journal • Preclinical

Antibiotic resistome and its driving factors in an urban river in northern China. (PubMed, Sci Total Environ) - "Moreover, random forest algorithm explored that WT, Ni, DO, Co, and polyether and macrolide antibiotics were the main drivers (>10 %) of ARGs dissemination in water, whereas the transposase genes of Tp614, tnpA, and IS613 were the main drivers of ARGs dissemination in both water and sediment. This study provides a comprehensive understanding of the driving factors for the ARGs dissemination in an urban river, which is of great significance for risk management of antibiotic resistome."

Journal

Iguratimod Inhibits Skin Fibrosis by regulating TGF-β1/Smad Signaling Pathway in Systemic Sclerosis. (PubMed, Eur J Clin Invest) - "Our preliminary data indicated T614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF-β1/smad pathway in experimental SSc models and may be a promising therapeutic agent for SSc."

Journal • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • SMAD3 • TGFB1

Comparative analysis of antibiotic resistance genes on a pig farm and its neighboring fish ponds in a lakeside district. (PubMed, Environ Pollut) - "Based on network analysis, we found that total phosphorus and Tp614 were the most important WIs and MGEs affecting ARG abundance, respectively. Our findings provide fundamental data on farms in lakeside districts and provide insights into establishing standards for the discharge of aquaculture wastewater."

Journal

[VIRTUAL] Randomised, Double-blind, Placebo-controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis (ACR-CONVERGENCE 2021) - "Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good."

Clinical • Ankylosing Spondylitis • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • IL17A

Effect of cattle farm exposure on oropharyngeal and gut microbial communities and antibiotic resistance genes in workers. (PubMed, Sci Total Environ) - "Overall, our results indicated that farm exposure may have affected the microbial composition and increased ARG abundance of farmworkers. Transmission of some ARGs may have occurred among the environment, animals and humans via host bacteria, which might pose a potential threat to human health."

Journal

The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment (clinicaltrials.gov) - P4; N=200; Active, not recruiting; Sponsor: Qilu Hospital of Shandong University; Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Effectiveness of drug safety measures for reducing the incidence of adverse drug reactions: Post-hoc analysis of data from all-case surveillance of iguratimod using generalized estimating equations. (PubMed, PLoS One) - "After implementing precautions regarding co-administration with warfarin and liver dysfunction, the estimated mean incidence rate of adverse drug reactions (95% confidence interval) decreased significantly to 0.73 (0.59-0.90) and 0.72 (0.55-0.94), respectively. Accordingly, some of the implementation of safety measures significantly reduced adverse drug reactions. The effectiveness of safety measures implemented during the all-case surveillance of iguratimod was evaluated, revealing that early implementation of safety measures decreased the incidence of adverse drug reactions."

Adverse drug reaction • Clinical • Journal • Retrospective data • Hepatology • Liver Failure

The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA (clinicaltrials.gov) - P4; N=100; Recruiting; Sponsor: Qilu Hospital of Shandong University

New P4 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway. (PubMed, J Orthop Surg Res) - "Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage."

Journal • Immunology • Inflammation • Oncology • Osteoarthritis • Pain • Rheumatology • IL6 • MMP13 • TNFA

T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro. (PubMed, Vascular) - "In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA."

Journal • Preclinical • Immunology • Inflammation

Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-label extension of a randomized, double-blind, placebo-controlled trial. (PubMed) - "No deaths occurred. Efficacy and tolerance of iguratimod + MTX therapy was maintained to 52 weeks in patients with active RA with inadequate response to MTX."

Journal • Biosimilar • Immunology • Inflammation • Rheumatoid Arthritis

Iguratimod in Kidney Transplant Recepients (clinicaltrials.gov) - P=N/A; N=60; Recruiting; Sponsor: The First Affiliated Hospital with Nanjing Medical University; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Immunology