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FDA Approves Lodoco, First Anti-Inflammatory Drug For Cardiovascular Disease. Here's Why It's A Big Deal
The Food and Drug Administration (FDA) has approved the first-ever anti-inflammatory drug for cardiovascular disease.
Called LODOCO (colchicine, 0.5mg), the recently approved medication has been shown to reduce cardiac event risk in adults with atherosclerotic cardiovascular disease (ASCVD) or with multiple risk factors for cardiovascular disease by an additional 31% compared to standard-of-care treatment. This means colchicine can be used in the prevention and treatment of cardiovascular disease.
The FDA-approval is supported by data from a multi-national, randomized, double-blind, placebo-controlled clinical trial including 5,522 people with chronic coronary disease taking guideline-directed medical care including high-intensity statins.
In the study's findings, LODOCO was shown to reduce risk of:
LODOCO can be used alone or in combination with cholesterol-lowering medications.
"We have known for a number of years about the role of inflammation in the development of plaque buildup in the arteries," says Dr. Brett Nowlan, a cardiologist with Hartford HealthCare Heart & Vascular Institute.
"Up until this new approval of colchicine, we did not have any medications in the cardiac field to specifically address this risk."
Nowlan also explains the anti-inflammatory mechanisms at work in colchicine are different from other medications such as steroids, or NSAIDs like aspirin.
"It is a pill intended to be taken once per day and is a long-term preventive medication. It would be added on to any other risk-reducing medications, such as aspirin or statins, and would not replace use of these," he notes.
"Although we have long suspected inflammation as playing a major role in the development of coronary disease, it was only in the last 10 years that major trials have come out which showed how useful an anti-inflammatory such as colchicine could be in reducing the cardiovascular risk in patients with heart disease," says Dr. Cheng-Han Chen, PhD, interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, California.
"The drug works through multiple pathways to decrease the activity of our different types of inflammatory cells. In doing so, it has been shown to reduce such serious risks as heart attack and stroke," says Chen.
"Interestingly, colchicine is not a new medication," says Chen.
"It has been used widely for different inflammatory conditions throughout the body such as gout and liver inflammation," says Dr. Chen. Nowlan adds it's also used for pericarditis or reducing inflammation of the fibrous sac lining around the heart.
"The reason this FDA approval is such a game changer is that we now believe it can be very useful in cardiovascular disease, specifically in patients we are already treating with our whole arsenal of efficacious heart medications such as statins," Chen tells Healthline.
"We now have a way to treat the disease through a different angle that we never used before, which is through attacking underlying inflammation," says Chen.
"With colchicine, we now have a unique way of lowering cardiovascular risk, which adds to and complements other medications that we currently use," says Nowlan. This treatment results from the study compare very well with other medications we use, he adds.
"As with all medications, colchicine is not right for everyone," says Nowlan. "The most common side effect with this medication is gastrointestinal upset."
"There are also uncommon but known effects of colchicine of lowering blood cell counts, and causing muscle weakness," he says.
"[Colchicine] can also interfere with levels of medications such as some antifungal and antibiotic drugs," Nowlan adds.
Common side effects reported in clinical studies according to the FDA:
Serious side effects, including death, are associated with taking more than the recommended dose. Colchicine overdose can lead to the following:
The FDA says to keep colchicine out of reach of children.
Nowlan tells Healthline the approval of colchicine also highlights the importance of inflammation as a risk factor for heart disease and should encourage everyone to make lifestyle choices that can help lower inflammation. He says these include:
When it comes to eating more whole and unprocessed foods or eating to reduce inflammation, the American Heart Association suggests the Mediterranean diet, which has been shown to lower the risk of heart disease and stroke.
The FDA recently approved the first anti-inflammatory drug for cardiovascular disease called LODOCO (colchicine).
The recently approved medication has been shown to reduce cardiac event risk in adults with atherosclerotic cardiovascular disease (ASCVD) or with multiple risk factors for cardiovascular disease by an additional 31% compared to standard-of-care treatment.
LODOCO can be used alone or in combination with cholesterol-lowering medications.
Anti-inflammatory Drugs May Hold Potential In Alzheimer's Treatment
To understand how blocking the production of p38 protein could help with Alzheimer's disease, the researchers conducted tests on an early-stage mouse model of Alzheimer's disease.
In this new study, published in PLOS ONE, the researchers used genetic techniques to stop the production of p38 in a specific type of immune cell found in the brain called microglia.
The researchers wanted to see if this intervention could change the way amyloid plaques, which are a key feature of Alzheimer's, develop in the brain.
The p38 alpha mitogen-activated protein kinase (p38-alpha) is a type of protein in our body that plays a role in our immune system's responses and is involved in both our immediate defense mechanisms and the more targeted responses of our immune system.
Scientists are studying this protein as a potential target for developing drugs to treat Alzheimer's disease and other conditions where there are problems with inflammation in the brain.
In animal studies, it has been observed that inhibiting or blocking p38-alpha can help protect against the damage associated with Alzheimer's disease. However, we still do not fully understand all the ways in which this happens.
The drugs that inhibit p38-alpha might be helpful because they can regulate the way certain brain cells called microglia respond to inflammation.
These microglia are involved in the inflammatory processes that contribute to the development of Alzheimer's disease.
Although the plaques themselves were not directly influenced by blocking p38, the researchers noticed that the number of microglia cells near these plaques decreased.
This suggests that when p38 production is suppressed in microglia, it may affect how these cells interact with the aspects of Alzheimer's disease pathology, including amyloid plaques.
Certain types of anti-inflammatory drugs, such as p38 inhibitors, are being developed as potential treatments for Alzheimer's disease. These drugs have shown promising results in recent clinical trials involving human participants.
However, there are still questions to be answered, for example, when exactly during the progression of Alzheimer's disease these p38 inhibitors should be administered to be most effective.
It would also be important to determine whether long-term suppression of p38 could have any negative effects on the body, although early results suggest that it does not seem to cause any noticeable harmful effects.
The findings from the research suggest that early use of p38 inhibitors may be able to change how immune cells in the brain interact with Alzheimer's disease-related changes.
Dr. Santosh Kesari, a neurologist at Providence Saint John's Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, not involved in this research, told Medical News Today that "inflammation is thought to play a role in neurodegenerative disorders and this article tested whether p38 protein in brain microglia is involved in Alzheimer's pathology in a mouse model."
"Microglia p38 modulates in immune responses in brain pathologies. The authors knocked out p38 in microglial specifically to see how it affected behavioral and pathological changes in [an] amyloid Alzheimer's model," Dr. Kesari explained.
"Interestingly, the p38 loss in microglia did not alter behavioral outcomes, information levels, or amyloid plaque levels despite increase in levels of [beta-amyloid-42] and distribution of microglial around plaques."
– Santosh Kesari
Dr. Raymond J. Tesi, CEO and chief medical officer at INmune Bio, also not involved in the study, also reviewed the findings for MNT, saying that his "conclusion is that blocking the p38a pathway in this animal model did not have any effect on cognitive function."
Dr. Kesari pointed out that "this is an early study exploring the role of microglial p38 in amyloid formation and dementia."
"While p38 loss shows subtle effects in brain pathology, more studies will need to be done to see how significant this protein is in Alzheimer's related pathology and if it represents a good target for future drug development to treat Alzheimer's and other related dementias," Dr. Kesari explained.
Dr. Tesi went further, saying that "INmune Bio does not believe amyloid plaques are a therapeutic drug target, but a biomarker of disease."
"Put in simple English, we are not surprised that cognition was not altered by plaque burden because it is not part of the pathophysiology of the disease."
"An implication for humans may be that amyloid plaques are not related to cognitive function. This is consistent with the observation that many people die with amyloid plaques in their brains and normal cognitive function."
– Dr. Raymond J. Tesi
Ultimately, more research is needed.
Commonly Used Gout Drug Found Effective Against COVID-19
An anti-inflammatory drug commonly used to treat gout could significantly improve outcomes in patients with mild-to-moderate COVID-19 infections, according to research by a team led by University of Georgia professor Ralph Tripp.
In a dose-range study of probenecid, a drug originally approved in 1951 to prevent the production of gout-causing uric acid, researchers showed significant improvements both in preventing the transmission of COVID-19 and the speed at which symptoms cleared in patients. In comparison to other FDA-approved drugs used to treat the virus, probenecid helped clear symptoms several days faster, Tripp said.
"This is a significant development," said Tripp, a professor in the College of Veterinary Medicine and a Georgia Research Alliance Eminent Scholar. "It shows improvement in both virus clearance and symptom reduction."
TrippBio, the biotechnology company co-founded by Tripp and colleagues, enrolled 75 non-hospitalized patients with mild-to-moderate COVID-19. The patients were divided into three groups: one receiving 500 milligrams of probenecid twice daily, another receiving 1,000 mg twice daily and a third receiving a placebo twice daily for five days. Symptoms were recorded incrementally over the course of 28 days to assess progress.
None of the 75 patients who completed the study were hospitalized, and the group receiving the twice-daily 500 mg treatment showed a two-day improvement (nine days compared to 11) in viral clearance over the placebo. Importantly, the 1,000 mg treatment doubled the clearance improvement to four days, resulting in an average recovery time of seven days. Patients treated with probenecid also showed improvements within three to five days after contracting the virus.
The most effective treatment, Tripp said, is for patients to take 1,000 mg tablets twice daily for approximately five days.
The study included patients aged 18-65 who experienced mild to moderate symptoms. Tripp classified "mild" as a patient who has tested positive for the infection using a PCR test and exhibited symptoms such as elevated body temperature, reduced oxygen saturation, decreased respiratory rate and other conditions outlined by the World Health Organization. The study demonstrated improvements in each of these areas.
Long used as a treatment for gout, probenecid has sparked interest in its potential to treat respiratory illnesses in both children and elderly patients. Development of oral tablets and syrup forms of the drug is being considered, and further testing is needed to determine whether a higher dosage or improved solubility could enhance results.
Tripp also suggested testing was needed to confirm the effectiveness of the drug against other respiratory viruses. The drug has shown strong activity against both influenza and respiratory syncytial virus (RSV) in laboratory and animal studies.
TrippBio, a company based on decades of research by Tripp, identifies new applications for existing drugs. The UGA Research Foundation is a major shareholder of the company.
The paper is published in the journal Viruses.
More information: David E. Martin et al, Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19, Viruses (2023). DOI: 10.3390/v15071508
Citation: Commonly used gout drug found effective against COVID-19 (2023, July 27) retrieved 30 July 2023 from https://medicalxpress.Com/news/2023-07-commonly-gout-drug-effective-covid-.Html
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