Day: January 25, 2021

Categories : AgeingTags :

For Older IBD Patients, Vedolizumab is a Safer Option

On By ModernMedia

Vedolizumab appeared to be safer than tumour necrosis factor (TNF) inhibitors in older adults with inflammatory bowel disease (IBD), according to the results of a large retrospective study.

Vedolizumab is a fully humanised monoclonal antibody which targets α4β7 integrin, and prevents leukocyte movement from the blood into inflamed gut tissue.

At the virtual Crohn’s and Colitis Congress, Bharati Kochar, MD, of Massachusetts General Hospital in Boston, presented data showing that all-cause hospitalisation during the 12 months after initiating biologic treatment was lower in new users of vedolizumab than in those starting TNF inhibitors, with a hazard ratio of 0.81 (95% CI 0.68-0.96)

“The American population is rapidly aging, and the number of Americans 65 and older in 2060 will be more than double what it was in 2014,” Dr Kochar said. “The combination of increasing IBD incidence, improvements in disease treatment-related knowledge, and decreasing IBD mortality is resulting in a high prevalence of older adults with IBD,” she added.

It is estimated that a quarter of Americans over 65 have IBD, yet are less likely to receive adequate immunosuppression. Over 65s are underrepresented in IBD clinical trials, creating a lack of understanding over what medications work or not in this age group.

To answer this question, Dr Kochar and her team analysed a 20% sample of Medicare claims database. Patients were included if they were diagnosed with Crohn’s disease or ulcerative colitis and if they initiated treatment with vedolizumab, infliximab, adalimumab, golimumab, or certolizumab from 2014 to 2018 after being on Medicare for 12 months while not receiving any of those medications.

There were 488 new users of vedolizumab and 2213 initiators of TNF inhibitors in the analysis group, with an average age of 71. More than half were women and most were white, 44% had ulcerative colitis and over half of patients had Carlson Comorbidity Index scores of 2 or higher.

There was otherwise no significant difference between vedolizumab and TNF for IBD-related hospitalisation (HR 0.77, 95% Ci 0.53-1.12), IBD-related surgery: (HR 0.78, 95% CI 0.49-1.22), or new steroid prescription within 60 days of starting the biologic (HR 1.01, 95% CI 0.86-1.18).

In the 6-month period prior to biologic initiation, nearly one-third had a prescription for budesonide, 58% had a prescription for a systemic corticosteroid, and nearly one-third were being prescribed immunomodulators.

“In conclusion, I think it’s important to use your clinical judgment to treat the patient in front of you, and these data should simply help contextualise risk for older IBD patients newly initiating vedolizumab or TNF inhibitors,” said Dr Kochar.

“There is a vast need for additional large and robust comparative effectiveness and safety studies for older adults with IBD, with the rapid proliferation of new IBD medications,” she concluded.

Source: MedPage Today

Presentation information: Kochar B, et al “Comparative effectiveness and safety of vedolizumab and anti-tumor necrosis factor agents in older adults with inflammatory bowel diseases in Medicare administrative claims database” CCC 2021

Categories : COVID Immune SystemTags :

NSAIDs Suppress Antibodies in COVID Infections

On By ModernMedia

A new study has found that non-steroidal anti-inflammatory drugs (NSAIDs) suppress antibody counts as well as inflammatory levels in mice infected with the SARS-CoV-2 virus.

NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are needed for prostaglandin generation – lipid molecules involved in homeostasis and inflammation. The study used ibuprofen and meloxicam in mice infected with SARS-CoV-2. The researchers aimed to observe: viral infection through modified expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2, effects on viral replication and modulated response of the immune system. However, they did not observe altered viral infection or replication.

“NSAIDs are arguably the most commonly used anti-inflammatory medications,” said principal investigator Craig B Wilen, Assistant Professor of Laboratory Medicine and Immunology, Yale University School of Medicine.

As well as taking NSAIDs for chronic conditions, eg arthritis, people take them “for shorter periods of time during infections, and [during] acute inflammation as experienced with COVID-19, and for side effects from vaccination, such as soreness, fever, and malaise,” Dr Wilen explained.

“Our work suggests that the NSAID meloxicam dampens the immune response to SARS-CoV-2 infection. Taking NSAIDs during COVID-19 could be harmful or beneficial, depending on the timing of administration,” said Dr Wilen. Dexamethasone, a potent anti-inflammatory but not an NSAID, is detrimental when administered at early stages of COVID but beneficial at later stages. NSAIDs may similarly be detrimental at the early stage because they counteract beneficial inflammation.

An antibody reduction by NSAIDs might not be harmful, but it could also reduce the immune system’s ability to mount a defence early on, or even reduce the length or magnitude of immunity or vaccination protection, Dr Wilen said. Antipyretics such as paracetamol have also been observed to blunt immune system response to vaccination.  

According to Dr Wilen, the original motivation from the study “was a twitter thread, suggesting NSAIDs should not be used during COVID-19. This seemed suspicious to us, so we wanted to investigate.”

Dr Wilen and his team believed there would be no effect of NSAIDs on viral infection, which turned out to be correct. However, they also thought there would be no effect on antibody response.

“In fact, we initially didn’t even carefully look at the antibody response, because we didn’t expect it to be altered by NSAIDs. This turned out to be wrong,” commented Dr Wilen.

Source: Medical Xpress

Journal information: Jennifer S. Chen et al. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection, Journal of Virology (2021). DOI: 10.1128/JVI.00014-21

Categories : Expert Opinion Medical IndustryTags :

Like 60s Cars, Brand Drugs Have no Price Competition

On By ModernMedia

Brand name drugs, like American cars in the 1960s, are subject to broadly rising prices with little evidence of competing on cost.

Before the oil embargo by Arab countries in 1973 allowed competition from more affordable, fuel efficient cars that we take for granted today, the Big Three car manufacturers, Ford, Chrysler and General Motors, would annually announce price increases at about the same time. Any adjustment by one manufacturer, for example, in size, was quickly matched by competitors.New research analysed the prices for five classes of drugs, and found them to be increasing in lock-step from 2015 to 2020. These classes are direct-acting oral anticoagulants (DOACs), P2Y12 inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl dipeptidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein-2 (SGLT-2) inhibitors.

The study had limitations due to not taking into account measures such as rebates, which would affect the price for the patient. However, even if these were taken into consideration, the researchers believe the overall prices would still increase and have to be borne by some patients who would not benefit from certain rebates. “Rebates, list prices, and net prices have been growing for brand-name medications, and rebate growth has been shown to positively correlate with list price growth, thereby impacting costs faced by patients paying a percentage of (or the full) list price,” the researchers noted. “Therefore, the lock-step price increases of brand-name medications, without evidence of price competition, raise concerns and would be expected to adversely affect patient adherence to medications and thus clinical outcomes.”

Unlike the oil crisis which broke open the automobile market to foreign competitors, the solution with “Big Pharma” is less clear. The researchers recommend policies which would limit such lock-step price increases, reduced patent exclusivity periods, and quicker introduction of generic equivalents.

Source: MedPage Today

Journal information: Liu P, et al “Trends in Within-Class Changes in US Average Wholesale Prices for Brand-Name Medications for Common Conditions From 2015 to 2020” JAMA Netw Open 2021; DOI: 10.1001/jamanetworkopen.2020.35064.

Categories : Uncategorized

Exercise can Block Muscle Wasting from Chronic Inflammation

On By ModernMedia

In yet another discovery pointing to the benefits of physical activity, human muscle has been shown to stave off the destructive effects of chronic inflammation through exercise.

“Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person,” said Nenad Bursac, professor of biomedical engineering at Duke. “Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own.”

Inflammation can be beneficial, such as a low-level response which clears out debris and helps regeneration, or it can be detrimental, such as the lethal COVID cytokine storms. Chronic inflammation as in arthritis or sarcopenia can be damaging as it takes away the ability of muscle to contract, resulting in weakening.

One inflammatory molecule in particular, interferon gamma, has been shown to be associated in many different types of muscular wasting. Interferon gamma is primarily produced by T lymphocytes and natural killer (NK) cells.

“We know that chronic inflammatory diseases induce muscle atrophy, but we wanted to see if the same thing would happen to our engineered human muscles grown in a Petri dish,” said Zhaowei Chen, a postdoctoral researcher in Bursac’s laboratory and first author of the paper. “Not only did we confirm that interferon gamma primarily works through a specific signaling pathway, we showed that exercising muscle cells can directly counter this pro-inflammatory signaling independent of the presence of other cell types or tissues.”

To determine if interferon gamma was the true culprit, Berac and Chen grew contractile human muscle tissue in vitro, then flooded it with interferon gamma over seven days. As predicted, the muscle shrank and lost strength,

They then applied interferon gamma again, but this time electrically stimulating the muscle to contract. They expected the simulated exercise to result in some muscle regrowth as seen in their previous studies, but to their surprise, the muscle suffered almost no effect from the chronic inflammation.They demonstrated that exercise blocked a particular molecular pathway as used in a pair of drugs to treat rheumatoid arthritis, tofacitinib and baricitinib, which produce the same anti-inflammatory effect.

“When exercising, the muscle cells themselves were directly opposing the pro-inflammatory signal induced by interferon gamma, which we did not expect to happen,” Bursac said. “These results show just how valuable lab-grown human muscles might be in discovering new mechanisms of disease and potential treatments. There are notions out there that optimal levels and regimes of exercise could fight chronic inflammation while not overstressing the cells. Maybe with our engineered muscle, we can help find out if such notions are true,” Bursac concluded.

Source: Medical Xpress

Journal information: Z. Chen el al., “Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle,” Science Advances (2020). advances.sciencemag.org/lookup … .1126/sciadv.abd9502

Categories : COVID Immune SystemTags :

New “Double Antibodies” can Treat COVID Variants

On By ModernMedia

A new generation of “double antibodies” has been developed which can protect against all SARS-CoV-2 variants, as well as inhibiting mutations against the antibodies.

These “bispecific”  antibodies were created by the Institute for Research in Biomedicine (IRB; Bellinzona, Switzerland), which is affiliated to the Università della Svizzera italiana (USI).

While traditional antibody-based immunisation is able to offer protection against SARS-CoV-2, there is still a need to protect against variants which may achieve “vaccine escape”, as well as inhibiting mutations which give rise to resistance, as with antibiotic resistance in bacteria.

The researchers overcame these difficulties by splicing together a pair of antibodies to make a “bispecific” antibody that simultaneously targets two viral sites. The bispecific antibody treatment has proved effective in mouse models, which maintained body weight when infected with SARS-CoV-2, compared to infected controls, which lost 20-30% body weight before humane euthanisation. The paper is available on the bioRxiv preprint server.

Study author Luca Varani of USI explained: “We exploited our knowledge of the molecular structure and biochemical traits of the virus to fuse together two human antibodies, obtaining a single bispecific molecule simultaneously attacking the virus in two independent sites critical for infectivity. Supercomputing simulations allowed us to refine and validate the bispecific antibody design, which was later produced and tested in the laboratory. Although the virus can mutate and escape from the attack of a single first-generation antibody, we have shown that it cannot do so against the double action of the bispecific.

“A single injection of the bispecific antibody provides instantaneous protection against the disease in pre-clinical trials. The antibody effectively reduces viral burden in the lungs and mitigates inflammation typical of COVID-19”, said Daniel Ruzek from the Czech Academy of Sciences who led the antibody pre-clinical testing.

The effectiveness of the bispecific antibodies holds promise for human clinical trials, with the prospect of being both an effective prevention and treatment of COVID.

Source: News-Medical.Net

Journal information: Gasparo, R D., et al. (2020) Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease. bioRxiv.doi.org/10.1101/2021.01.22.427567.