scholarly journals Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials

2021 ◽  
Vol 16 ◽  
Author(s):  
Alberto J Lorenzatti
Keyword(s):  
Clinical Trials ◽  
Arterial Wall ◽  
Plaque Formation ◽  
Phase Iii ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Phase Iii Clinical Trials ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. The results from the pivotal CANTOS trial show that targeting the pro-inflammatory cytokine IL-1β successfully reduces the incidence of secondary CV events. This review briefly assesses the role of inflammation in atherosclerosis, providing a picture of the multiple players involved in the process and offering a perspective on targeting inflammation to prevent atherosclerotic CV events, as well as focusing on the results of the latest Phase III clinical trials.

scholarly journals The role of data and safety monitoring boards in implementation trials: When are they justified?

2020 ◽  
Vol 4 (3) ◽  
pp. 229-232
Author(s):  
Kevin Fiscella ◽  
Mechelle Sanders ◽  
Tameir Holder ◽  
Jennifer K. Carroll ◽  
Amneris Luque ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Safety Monitoring ◽  
National Institutes Of Health ◽  
Phase Iii ◽  
Blood Institute ◽  
Phase Iii Clinical Trials ◽  
National Heart Lung ◽  
Cooperative Agreements ◽  
Monitor Data

AbstractThe National Institutes of Health requires data and safety monitoring boards (DSMBs) for all phase III clinical trials. The National Heart, Lung and Blood Institute requires DSMBs for all clinical trials involving more than one site and those involving cooperative agreements and contracts. These policies have resulted in the establishment of DSMBs for many implementation trials, with little consideration regarding the appropriateness of DSMBs and/or key adaptations needed by DSMBs to monitor data quality and participant safety. In this perspective, we review the unique features of implementation trials and reflect on key questions regarding the justification for DSMBs and their potential role and monitoring targets within implementation trials.

scholarly journals A perspective on targeting inflammation and cytokine actions in atherosclerosis

2020 ◽  
Author(s):  
Yee-Hung Chan ◽  
Dipak P Ramji
Keyword(s):  
Modern Society ◽  
Phase Iii ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Phase Iii Clinical Trials ◽  
Future Challenges ◽  
Recent Phase ◽  
Key Driver ◽  
Outcomes Study ◽  
Significant Health

Atherosclerosis, a chronic inflammatory disorder of the vasculature that results in cardiovascular disease, continues to pose a significant health and economic burden on modern society. Whilst inflammation has generally been accepted as the key driver of all stages of the disease, it was not until recently that inhibition of a specific proinflammatory cytokine (IL-1β) yielded successful results in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study trial. This article offers a perspective on targeting inflammation for atherosclerosis, focusing on results of recent Phase III clinical trials, and discusses other potential candidates together with future challenges and prospects.

scholarly journals Ustekinumab in psoriatic arthritis and related phenotypes

2018 ◽  
Vol 9 (10) ◽  
pp. 191-198 ◽  
Author(s):  
Isobel Dobbin-Sears ◽  
Janet Roberts ◽  
Darren D. O’Rielly ◽  
Proton Rahman
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Clinical Efficacy ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Clinical Trials ◽  
Th 17 ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs

Psoriatic arthritis (PsA) is an inflammatory arthritis that commonly occurs with psoriasis and is attributed to genetic, immunologic and environmental factors. The T-helper (Th)-17 pathway and the interleukin (IL)-23/IL-17 axis have become prominent players in PsA and considerably increased our understanding of disease pathogenesis. In this review article, we will focus on the emerging role of IL-12/23 and its blockade, in the pathogenesis and management of PsA as well as of psoriasis and inflammatory bowel disease. Ustekinumab, is a fully human monoclonal immunoglobulin (Ig)G1 antibody that binds specifically to the p40 subunit of IL-12 and IL-23, primarily inhibiting downstream Th-17 signalling pathways. Ustekinumab produced consistent and sustained clinical efficacy in two phase III clinical trials in PsA, PSUMMIT-1 and PSUMMIT-2, with data out to 52 weeks, and no new safety signals. PSUMMIT-1 included patients with active PsA despite conventional therapy who were all naïve to anti-tumour necrosis factor (TNF) agents, whereas PSUMMIT-2 also included anti-TNF experienced patients. Similarly, ustekinumab produced consistent clinical efficacy in two phase III clinical trials in psoriasis, PHOENIX-1 and PHOENIX-2, and in both induction and maintenance of moderate-to-severe Crohn’s disease, UNITI-1, UNITI-2 and IM-UNITI, without an increased safety signal. Currently, ustekinumab is used in the treatment of PsA following the failure of nonsteroidal anti-inflammatory drugs (NSAIDs) and conventional disease-modifying antirheumatic drugs (DMARDs), and as an alternative to, or after failure of an anti-TNF agent.

scholarly journals An Update on the Leading COVID-19 Vaccines

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Ahmed Eladely ◽  
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Vaccine Development ◽  
Vaccine Safety ◽  
Clinical Development ◽  
Phase Iii ◽  
Phase Iii Clinical Trials

We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy.

scholarly journals B-cell–targeted therapies in relapsing forms of MS

2017 ◽  
Vol 4 (6) ◽  
pp. e405 ◽  
Author(s):  
Divyanshu Dubey ◽  
Thomas Forsthuber ◽  
Eoin P. Flanagan ◽  
Sean J. Pittock ◽  
Olaf Stüve
Keyword(s):  
Clinical Trials ◽  
B Cells ◽  
B Cell ◽  
Therapeutic Strategies ◽  
Phase Iii ◽  
B Cell Depletion ◽  
Pathogenic Role ◽  
Phase Iii Clinical Trials ◽  
Anti Cd20

In recent years, there has been a significant increase in the therapeutic options available for the management of relapsing forms of MS. Therapies primarily targeting B cells, including therapeutic anti-CD20 monoclonal antibodies, have been evaluated in phase I, phase II, and phase III clinical trials. Results of these trials have shown their efficacy and relatively tolerable adverse effect profiles, suggesting a favorable benefit-to-risk ratio. In this review, we discuss the pathogenic role of B cells in MS and the rationale behind the utilization of B-cell depletion as a therapeutic cellular option. We also discuss the data of clinical trials for anti-CD20 antibodies in relapsing forms of MS and existing evidence for other B-cell–directed therapeutic strategies.

Rome I versus Rome II; Overlap in patients enrolled in tegaserod phase III clinical trials for irritable bowel syndrome (IBS)

2001 ◽  
Vol 120 (5) ◽  
pp. A284-A284
Author(s):  
B NAULT ◽  
S SUE ◽  
J HEGGLAND ◽  
S GOHARI ◽  
G LIGOZIO ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Irritable Bowel ◽  
Rome I

Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials

2001 ◽  
Vol 28 (6) ◽  
pp. 620-625 ◽  
Author(s):  
Pierre Falardeau ◽  
Pierre Champagne ◽  
Patrick Poyet ◽  
Claude Hariton ◽  
[Eacute]ric Dupont
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Naturally Occurring ◽  
Antiangiogenic Drug

scholarly journals Animal and Human Vaccines against West Nile Virus

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1073
Author(s):  
Juan-Carlos Saiz
Keyword(s):  
Clinical Trials ◽  
West Nile Virus ◽  
Vaccine Development ◽  
Phase Iii ◽  
West Nile ◽  
Specific Therapy ◽  
Phase Iii Clinical Trials ◽  
Neuroinvasive Disease ◽  
The Us ◽  
The Status

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.

scholarly journals The role of future treatments in the management of neovascular age-related macular degeneration in Europe

2021 ◽  
pp. 112067212110183
Author(s):  
Laurent Kodjikian ◽  
Carl Joe Mehanna ◽  
Salomon-Yves Cohen ◽  
François Devin ◽  
Sam Razavi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Real World Data ◽  
Phase Iii Clinical Trials ◽  
Age Related ◽  
Injection Frequency ◽  
Endothelial Growth Factor

Anti-vascular endothelial growth factor (VEGF) agents have transformed the management of patients with neovascular age-related macular degeneration (nAMD) over the past two decades. However, as more long-term real-world data become available, it is clear that treatment outcomes are inferior to those reported in large, controlled clinical trials. This is largely driven by undertreatment, that is, not maintaining a consistent injection frequency to achieve sustained VEGF suppression, whether due to patient non-compliance, an important injection burden, or non/incomplete anatomical response. Newer therapeutic advances under evaluation hold promise in achieving more, for less. We review the latest drugs currently in or having successfully finished phase III clinical trials, and determine their potential place in the management of patients with nAMD in Europe.

scholarly journals Matching comparisons of therapeutic efficacy suggest better clinical outcomes for patients treated with peginterferon beta-1a than with glatiramer acetate

2021 ◽  
Vol 14 ◽  
pp. 175628642097591
Author(s):  
Thomas F. Scott ◽  
Ray Su ◽  
Kuangnan Xiong ◽  
Arman Altincatal ◽  
Carmen Castrillo-Viguera ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Propensity Score ◽  
Clinical Outcomes ◽  
Glatiramer Acetate ◽  
Therapeutic Efficacy ◽  
Individual Patient Data ◽  
Patient Data ◽  
Phase Iii ◽  
Lower Probability ◽  
Phase Iii Clinical Trials

Background: Peginterferon beta-1a and glatiramer acetate (GA) are approved first-line therapies for the treatment of relapsing forms of multiple sclerosis, but their therapeutic efficacy has not been compared directly. Methods: Clinical outcomes at 2 years, including no evidence of disease activity (NEDA), for patients receiving peginterferon beta-1a 125 mcg every 2 weeks (Q2W) or GA 20 mg/ml once daily (QD) were compared by propensity score matching analysis using individual patient data from ADVANCE and CONFIRM phase III clinical trials. In addition, clinical outcomes at 1–3 years for patients receiving peginterferon beta-1a Q2W or GA 40 mg/ml three times a week (TIW) were evaluated using a matching-adjusted comparison analysis of individual patient data from ADVANCE and the ADVANCE extension study, ATTAIN, and aggregate patient data from the phase III GALA and the GALA extension studies. Results: Propensity-score-matched peginterferon beta-1a patients ( n = 336) had a significantly lower annualized relapse rate [ARR (0.204 versus 0.282); rate ratio = 0.724; p = 0.045], a significantly lower probability of 12-week confirmed disability worsening (10.0% versus 14.6%; hazard ratio = 0.625; p = 0.048), and a significantly higher rate of NEDA (20.3% versus 11.5%; p = 0.047) compared with GA 20 mg/ml QD patients after 2 years of treatment. Matching-adjusted peginterferon beta-1a patients (effective n = 276) demonstrated a similar ARR at 1 year (0.278 versus 0.318; p = 0.375) and significantly lower ARR at 2 years (0.0901 versus 0.203; p = 0.032) and 3 years (0.109 versus 0.209; p = 0.047) compared with GA 40 mg/ml TIW patients ( n = 834). Conclusion: Results from separate matching comparisons of phase III clinical trials and extension studies suggest that peginterferon beta-1a 125 mcg Q2W may provide better clinical outcomes than GA (20 mg/ml QD or 40 mg/ml TIW).

Sign in / Sign up

Export Citation Format

Share Document