- |||||||||| Tecfidera (dimethyl fumarate) / Biogen, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Biomarker, Journal: HDL-cholesterol elevation associated with fingolimod and dimethyl fumarate therapies in multiple sclerosis. (Pubmed Central) - Oct 31, 2019 Fingolimod and DMF therapies are associated with a specific increase in HDL in PwMS. Further studies are required to validate these findings and their potential implication as biomarker of reduced inflammatory state and/or reduced risk of neurodegeneration or cardiovascular comorbidity.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: Neuropsychiatric Systemic Lupus Erythematosus Is Dependent on Sphingosine-1-Phosphate Signaling. (Pubmed Central) - Oct 29, 2019 Furthermore, despite a reduction in splenomegaly, lymphadenopathy, and circulating autoantibody titers, IgG deposition within the brain was unaffected by treatment. These findings suggest that fingolimod mediates attenuation of NPSLE through a mechanism that is not dependent on reduction of autoantibodies or cytokines, and highlight modulation of the S1P signaling pathway as a novel therapeutic target in lupus involving the central nervous system.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: SPHK1-S1PR1-RANKL axis regulates the interactions between macrophages and BMSCs in inflammatory bone loss. (Pubmed Central) - Oct 26, 2019 Applying a potent S1P-S1PR1 signaling modulator, Fingolimod (FTY720), in a Wistar rat apical periodontitis model effectively prevented bone lesions in vivo via down-regulation of RANKL production, osteoclastogenesis, and bone resorption. Our data unveiled the regulatory role of SPHK1-S1PR1-RANKL axis in inflammatory bone lesions and proposed a potential therapeutic intervention by targeting this cell-signaling pathway to prevent bone loss.
- |||||||||| Xeljanz (tofacitinib) / Pfizer
Journal: Oral small molecules for psoriasis. (Pubmed Central) - Oct 25, 2019 Long-term safety data for apremilast suggest that it has a tolerable safety profile and leads to significant improvement in patients with psoriasis; however, there are few head-to-head comparisons with other oral systemic medications. Tofacitinib and ponesimod have demonstrated clinical efficacy in treating psoriasis; however, further studies are required to understand the benefit-risk profile of these medications in psoriasis patients.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Preclinical, Journal: Fingolimod therapy is not effective in a mouse model of spontaneous autoimmune peripheral polyneuropathy. (Pubmed Central) - Oct 24, 2019 In addition, fingolimod did not influence the functional outcome of CD86NOD mice compared to vehicle treatment nor any of the electrophysiological characteristics. In summary, we show that fingolimod treatment has no beneficial effects in autoimmune polyneuropathy, which is in line with recent clinical data obtained in CIDP patients.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe, carbamazepine / Generic Mfg.
Clinical, PK/PD data, Journal: Pharmacokinetic Interaction Between Fingolimod and Carbamazepine in Healthy Subjects. (Pubmed Central) - Oct 24, 2019 Models linking fingolimod-P blood concentrations to lymphocyte count or annual relapse rate suggest that such a decrease would have a low impact on the treatment effect. However, in the absence of efficacy data of fingolimod at doses lower than the therapeutic dose, their coadministration should be used with caution.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes. (Pubmed Central) - Oct 24, 2019 Moreover, the second curve derived from the high amplitude group exhibited a greater decrease in lymphocyte number after fingolimod treatment than the low amplitude group (p < 0.001). We suggest that the degree of decreased lymphocytes after fingolimod treatment (main effect) may be predicted by estimating the influence of degree in heart rate (side effect).
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: FTY720 restores endothelial cell permeability induced by malaria sera. (Pubmed Central) - Oct 18, 2019 The permeability increase induced by complicated P. falciparum sera was significantly reversed and prevented by FTY720 in vitro. FTY720 may have clinical applications to protect against endothelial barrier dysfunction in severe P. falciparum malaria.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Clinical, Journal: FTY720 Decreases Tumorigenesis in Group 3 Medulloblastoma Patient-Derived Xenografts. (Pubmed Central) - Oct 18, 2019 FTY720 decreased viability, proliferation, and motility in Group 3 medulloblastoma PDX cells and significantly decreased tumor growth in vivo. These results suggest that FTY720 should be investigated further as a potential therapeutic agent for medulloblastoma.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Synaptic Resilience to Psychosis in Alzheimer's Disease (Grand Ballroom 2) - Oct 17, 2019 - Abstract #ACNP2019ACNP_561; Mechanisms affecting either gene expression or transport of synaptic proteins may contribute to synaptic proteome compensation and resilience to psychosis in AD, as may enhanced neuronal metabolic capacity. Unique Data The data on RNAseq in DLPFC from psychotic and non-psychotic Alzheimer's disease subjects and the data fingolimod treatment of APPswe/PSEN1dE9 mice is new and unpublished.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Biomarker, Clinical, Journal: Predicting therapeutic response to fingolimod treatment in multiple sclerosis patients. (Pubmed Central) - Oct 16, 2019 Unique Data The data on RNAseq in DLPFC from psychotic and non-psychotic Alzheimer's disease subjects and the data fingolimod treatment of APPswe/PSEN1dE9 mice is new and unpublished. The results support that immune-monitoring of lymphocyte subpopulations in peripheral blood is a promising tool to select RRMS candidate for fingolimod treatment.
- |||||||||| iscalimab (CFZ533) / Novartis, tacrolimus / Generic Mfg.
Anti-CD40 (Iscalimab) Treatment Results in Preserved Allograft Histology in Non-Human Kidney Transplantation Compared with Calcineurin Inhibitors (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3426; Further, recent clinical data indicated that the anti-CD40 mAb Iscalimab (CFZ533) demonstrated comparable efficacy and superior renal function versus tacrolimus in de novo calcineruin inhibitor (CNI)-free kidney transplantation...Methods To further examine this notion, allograft histology from baseline and up to one hundred days post-transplanted NHP kidney allografts from transplanted animals treated with Iscalimab, anti-CD154 mAb, Cyclosporine A, PKC inhibitors or FTY720 were reviewed and scored in a blinded fashion by a pathologist according to the Banff classification...Conclusion Collectively our data indicated that prevention of allograft rejection by Iscalimab appears to be associated with higher graft quality compared to other drugs, including CNIs. Funding Commercial Support
- |||||||||| Leustatin (cladribine) / J&J, Mavenclad (cladribine) / EMD Serono
Review, Journal: Progressive multiple sclerosis: latest therapeutic developments and future directions. (Pubmed Central) - Oct 11, 2019 Moreover, some therapeutic approaches in preclinical stages are under development. In this review, we will summarize the newest therapeutic development in the field of progressive MS of the last 3 years, and shed light on auspicious substances with similar mechanisms and new developments in the therapeutic pipeline, presumably supporting a bright future for progressive MS treatment.
- |||||||||| TASP0277308 / Taisho, Mayzent (siponimod) / Novartis
Journal: Sphingosine 1-phosphate receptor subtype 1 (S1PR1) as a therapeutic target for brain trauma. (Pubmed Central) - Oct 9, 2019 Moreover, our findings provide pre-clinical evidence for the use of low dose oral S1PR1 antagonists as neuroprotective strategies for TBI and broaden our understanding of the underlying S1PR1-driven neuroinflammatory processes in the pathophysiology of TBI. Altogether, our results showed that blocking the S1PR1 axis is an effective therapeutic strategy to mitigate neuropathological effects engaged in the CNS by TBI.
- |||||||||| Clinical, Review, Journal: Cancer Risk in Patients with Multiple Sclerosis: Potential Impact of Disease-Modifying Drugs. (Pubmed Central) - Oct 8, 2019
Because of their action on the immune system, and due to a lack of available long-term data, a special warning of the potential risk of cancer accompanies the use of recent IS such as cladribine, fingolimod, natalizumab or alemtuzumab...For fingolimod, natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide, daclizumab and ocrelizumab, risk management plans outlined by regulatory agencies are mandatory...We review the current evidence behind the increased risk of malignancy in MS patients receiving DMTs, and provide an overview of the DMTs that are currently in use and those in clinical trials. The known risks and benefits of these therapies will be considered.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Clinical, Journal: Improving Outcomes in Pediatric Multiple Sclerosis: Current and Emerging Treatments. (Pubmed Central) - Oct 8, 2019 In this review, we discuss current evidence for MS therapies in children including the treatment of acute relapses, disease-modifying therapies, and symptomatic management. We will also discuss evidence for emerging therapies, including remyelinating and neuroprotective agents.
- |||||||||| Stelara (ustekinumab) / J&J
Analysis of Lupus Nephritis Gene Expression Reveals Dysregulation of Pathogenic Pathways Activated Within Infiltrating Cells (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3017; Blood antibody-secreting cells, potentially involved in SLE pathogenesis, were increased in patients with SLE and reduced by cenerimod treatment in the phase 2 clinical trial. Bioinformatic analysis of LN gene expression highlights several dysregulated signaling pathways that can form the targets of novel therapeutic strategies, and further elucidation of these signatures may enhance clinical surveillance and diagnosis of LN to improve patient outcomes.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Persistent Synovial Resident Memory T Cells Mediate Arthritis Flares (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1734; Synovial TRM cells persist in arthritic joints and retain their capacity to trigger a site-specific flare after prolonged periods of remission. Our data suggest that synovial resident memory T cells can mediate joint-specific memory in inflammatory arthritis and trigger flares by recruiting circulating lymphocytes, suggesting local depletion of TRM cells as a potential therapeutic strategy.
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