Useful message in choosing optimal biological agents for patients with autoimmune arthritis

Lai, Jenn‐Haung; Ling, Xiao Chun; Ho, Ling‐Jun

doi:10.1016/j.bcp.2019.03.007

Cited by 11 publications

(9 citation statements)

References 105 publications

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“…Patients that may benefit from new therapeutics which address limitations of existing treatments include those with autoimmune and inflammation-based diseases such as rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease (Crohn's), inflammatory vascular diseases, stroke, myocardial infarction, unstable angina, heart failure, sepsis, diabetes, renal failure and central nervous system trauma [21][22][23][24][25]. Other targets could include allograft transplant rejection, which is associated with elevated inflammatory serine proteases, chemokines and cytokines together with complement activation in the circulating blood and affected organs [26].…”

Section: Introductionmentioning

confidence: 99%

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Yaron

Zhang

Guo

et al. 2020

JCM

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Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as natural sources for immune modulators remains in the early stages of development. Viruses have evolved complex, highly effective approaches for immune evasion. Originally developed for protection against host immune responses, viral immune-modulating proteins are extraordinarily potent, often functioning at picomolar concentrations. These complex viral intracellular parasites have “performed the R&D”, developing highly effective immune evasive strategies over millions of years. These proteins provide a new and natural source for immune-modulating therapeutics, similar in many ways to penicillin being developed from mold or streptokinase from bacteria. Virus-derived serine proteinase inhibitors (serpins), chemokine modulating proteins, complement control, inflammasome inhibition, growth factors (e.g., viral vascular endothelial growth factor) and cytokine mimics (e.g., viral interleukin 10) and/or inhibitors (e.g., tumor necrosis factor) have now been identified that target central immunological response pathways. We review here current development of virus-derived immune-modulating biologics with efficacy demonstrated in pre-clinical or clinical studies, focusing on pox and herpesviruses-derived immune-modulating therapeutics.

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Section: Introductionmentioning

confidence: 99%

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Yaron

Zhang

Guo

et al. 2020

JCM

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“…Although significant advancements have been made in drug development for autoimmune arthritis in recent years, some patients remain to show inadequate therapeutic responses to the currently available csDMARDs and bDMARDs. Furthermore, with many different coexisting medical conditions, some bDMARDs appear to be inappropriate for use in treating patients with specific medical needs [107]. Because both the activation of the CD154-mediated costimulatory pathway in T cells and the stimulation of the CD40-mediated signaling pathway in B cells are critical in the pathogenesis of autoimmune arthritis, the introduction of CD40-CD154 blockade provides a wonderful opportunity for therapeutics of these disorders.…”

Section: Perspectivesmentioning

confidence: 99%

Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis

Lai

Luo

2019

Cells

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Full activation of T lymphocytes requires signals from both T cell receptors and costimulatory molecules. In addition to CD28, several T cell molecules could deliver costimulatory signals, including CD154, which primarily interacts with CD40 on B-cells. CD40 is a critical molecule regulating several B-cell functions, such as antibody production, germinal center formation and cellular proliferation. Upregulated expression of CD40 and CD154 occurs in immune effector cells and non-immune cells in different autoimmune diseases. In addition, therapeutic benefits have been observed by blocking the CD40-CD154 interaction in animals with collagen-induced arthritis. Given the therapeutic success of the biologics abatacept, which blocks CD28 costimulation, and rituximab, which deletes B cells in the treatment of autoimmune arthritis, the inhibition of the CD40-CD154 axis has two advantages, namely, attenuating CD154-mediated T cell costimulation and suppressing CD40-mediated B-cell stimulation. Furthermore, blockade of the CD40-CD154 interaction drives the conversion of CD4+ T cells to regulatory T cells that mediate immunosuppression. Currently, several biological products targeting the CD40-CD154 axis have been developed and are undergoing early phase clinical trials with encouraging success in several autoimmune disorders, including autoimmune arthritis. This review addresses the roles of the CD40-CD154 axis in the pathogenesis of autoimmune arthritis and its potential as a therapeutic target.

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“…TCZ is recommended in addition to dexamethasone, which has been widely adopted as standard of care based on findings from the RECOVERY trial [18] . TCZ half life is dose-dependent and estimated at 8-14 days [19] ; some recommendations suggest a repeat dose after 12-24 hours if there has not been sufficient clinical improvement [20] . Due to small overall numbers of COVID patients treated, limited prospective follow-up, and lack of concordance in reported clinical outcomes, guidance recognises the low certainty of the evidence and the pressing need for more data [7,21] .…”

Section: Introductionmentioning

confidence: 99%

Risk of reactivation of hepatitis B virus (HBV) and tuberculosis (TB) and complications of hepatitis C virus (HCV) following Tocilizumab therapy: A systematic review to inform risk assessment in the COVID era

Campbell

Andersson

Ansari

et al. 2021

Preprint

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Tocilizumab (TCZ), an IL-6 receptor antagonist, is used in the treatment of COVID. However, this agent carries a 'black box' warning for infection complications, which may include reactivation of tuberculosis (TB) or hepatitis B virus (HBV), or worsening of hepatitis C virus (HCV). Due to the pace of clinical research during the COVID pandemic, prospective evaluation of these risks has not been possible. We undertook a systematic review, generating mean cumulative incidence estimates for reactivation of HBV and TB at 3.3% and 4.3%. We could not generate estimates for HCV. These data derive from heterogeneous studies pre-dating the COVID outbreak, with differing epidemiology and varied approaches to screening and prophylaxis. We underline the need for careful individual risk assessment prior to TCZ prescription, and present an algorithm for clinical stratification. There is an urgent need for ongoing collation of safety data as TCZ therapy is used in COVID.

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Useful message in choosing optimal biological agents for patients with autoimmune arthritis

Cited by 11 publications

References 105 publications

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis

Risk of reactivation of hepatitis B virus (HBV) and tuberculosis (TB) and complications of hepatitis C virus (HCV) following Tocilizumab therapy: A systematic review to inform risk assessment in the COVID era

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