drug

Takeda Pharmaceutical’s dengue fever vaccine Qdenga expanded its approval to Europe after approval in Indonesia in August.

As Takeda continues to apply for vaccine licenses in dengue epidemic countries in Asia and Latin America, European approval is likely to have a positive effect on future approvals from other regulatory agencies.

Takeda announced on the 8th (local time) that the European Commission has approved the marketing of Qdenga in the European Union for the prevention of dengue fever in adults and children aged 4 years and older.

Qdenga is the only dengue vaccine available regardless of previous dengue exposure and should be used according to official recommendations.

Dengue fever was named as one of the top 10 threats to global health for 2019 by the World Health Organization (WHO) and is 30 times more prevalent than it was 50 years ago, covering more than 125 countries. Over the past 20 years, the worldwide incidence has increased eight-fold.

The approval follows the positive advisory opinion of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued last October.

The European Commission’s approval of Qdenga is based on the results of 19 phase 1, 2 and 3 clinical trials involving more than 28,000 children and adults. It includes four and a half years of follow-up data from the global pivotal phase 3 TIDES trial.

The TIDES trial met the primary endpoint of overall vaccine efficacy, showing that 80.2% of symptomatic dengue cases were prevented 12 months after two doses of the vaccine.

Qdenga also met key secondary endpoints, preventing 90.4% of hospitalizations after 18 months. Efficacy differed by serotype.

An exploratory analysis found that the vaccine prevented 84% of dengue hospitalizations and 61% of symptomatic dengue fever cases in the total population, including both seropositive and seronegative populations, over a 4.5-year follow-up period.

Vaccine tolerability was generally good, there was no evidence of disease enhancement in vaccinated persons, and no significant safety risks were found.

“European Commission approval is an important milestone for Qdenga, bringing us one step closer to achieving our aspiration to help reduce the global burden of dengue fever,” said Gary Durbin, President, Global Vaccines, Takeda.

Meanwhile, Qdenga was first approved in Indonesia in August of this year for the prevention of dengue against all serotypes for adults and children aged 6 to 45 years.

Research has shown that even professional and medical terminology that doctors use so commonly can lead to confusion in that many patients do not understand it.

Doctors or patients who have received some education have problems such as the fact that some patients perceive the content as completely opposite. Accordingly, it is the opinion of experts that standardized phrases are needed to narrow the gap.

On the 1st local time, the results of a large-scale study on the accuracy of patients’ understanding of medical terms were published in the Journal of the American Medical Association (JAMA) (10.1001/jamanetworkopen.2022.42972).

In actual clinical settings, the use of professional and medical terminology by doctors is accepted as an issue to be avoided. This is because confusion is inevitable in that there is a risk that the patient will not understand it properly.

However, in various studies, an unavoidable situation called ‘technical term oblivion’ has also been reported. This is when a doctor tries to avoid using specialized or medical terminology, but is unaware that the word itself is a technical term.

This is also the reason why a research team led by Professor Rachael Gotlieb of the University of Minnesota Medical School conducted a study on this gap. This is to find out whether real patients properly recognize these terms.

Accordingly, the research team showed 215 adults sentences using technical terms and sentences that did not, through short-answer and multiple-choice questions, and evaluated their level of understanding.

As a result, 96% of the patients who knew that it was not cancer for ‘Your cancer screening result was negative’ showed a higher understanding of positive and negative than expected.

However, only 79% of patients understood that the “tumor is progressing” explanation meant that the cancer was spreading. 21% didn’t think things were getting worse.

If you go a little more professionally, the level of understanding is greatly reduced. For example, only 80% of the phrase ‘there is no noticeable chest radiography result’ was recognized as positive news.

In particular, when asked to describe a chest radiograph as “impressive,” only 21% accepted the word as bad news. This means that 8 out of 10 people do not recognize it properly.

Likewise, only 41% of patients knew that being ‘neurologically sound’ was good news. Only 33% of respondents knew that their positive nodes had spread their cancer.

In that sense, the research team emphasized that the basis for the patient to better understand the doctor’s words is laid by paying very little attention.

For example, only 87% of patients understood the words ‘blood culture result is negative’, but 98% understood ‘blood test result is negative’.

Professor Rachel said, “It is meaningful in that it is the world’s first study to evaluate patients’ understanding of general professional and medical terminology,” and “It shows that doctors need to pay more attention to these areas.”

He continued, “For example, it is correct to use the word ‘don’t eat anything’ given that a quarter of patients do not understand the word ‘do not take oral intake’ properly.” It takes effort to think about phrases, etc.”

“In case of rheumatoid arthritis, early treatment is important as the future prognosis depends on the success of the initial 3-month treatment. As joint damage is an irreversible phenomenon, I want to emphasize proper treatment in the early stages of the disease before it loses function.”

Rheumatoid arthritis is a disease in which abnormally activated immune cells invade joints and cause inflammation and pain. If it is not detected early and is not treated appropriately, inflammation repeatedly occurs for a long time, resulting in deformation of the joint and loss of function.

Chungnam National University Hospital Rheumatology Professor Shim Seung-cheol emphasized treatment through early diagnosis to increase the treatment effect of rheumatoid arthritis.

Rheumatoid arthritis is one of the most common autoimmune diseases and occurs in less than 1% of the total population.

According to the statistics of the Health Insurance Review and Assessment Service, there were a total of 238,984 patients with rheumatoid arthritis in 2020, and when it was detailed, there were 180,076 women and 58,908 men, three times more female patients.

Professor Shim said, “An autoimmune disease is an abnormal reaction of immune cells that protect our body, which attacks various organs or tissues of the body. Among them, rheumatoid arthritis attacks joints as a target. Treatment is also based on these scientific phenomena. “We use treatments that suppress the immune system’s misdirection to attack,” he said.

Recently, the treatment of rheumatoid arthritis has been able to prevent joint damage with the development of various drugs, and in particular, the development of targeted therapies has improved the treatment effect.

However, as the number of weapons that can be used has increased compared to the past, Professor Shim explains that the question of which drug is best to use for which patient has deepened.

Professor Shim said, “If methotrexate is used, 70% of patients are effective, and if there is no response, 70% of them will improve if biological agents are used. About 10% of all patients were difficult to treat.” “However, unlike biological agents, the development of Janus kinase (JAK) inhibitors, which block inflammatory signals within cells, has made it possible to treat these patients, and we are gradually increasing the experience of using them,” he said.

However, it is also true that the approval of related drugs was changed as the cardiovascular safety issue of JAK inhibitors was raised.

Regarding this, Professor Shim explained, “Other drugs have gone through the same process in the past, but I believe that this barrier can be overcome if the appropriate patient group is selected and treated in consideration of safety.”

He continued, “I think it is right to give some authority to experts who treat patients in the field rather than limiting the use of drugs entirely by the government.” If it is found, it will be possible to set detailed treatment guidelines for it.”

At the same time, his view is that early diagnosis, which detects the disease as early as possible, is important in order to increase the treatment effect.

Professor Shim said, “Personally, joints and bones must be treated before they lose their function, and to do so, early diagnosis is important.” Patients with negative rheumatoid factor are diagnosed late and do not receive insurance benefits even after diagnosis, so I think that this part needs improvement,” he said.

“Rheumatoid arthritis has no diagnostic criteria yet and classification criteria are used, so it is difficult to diagnose early in clinical practice,” he advised.

Professor Shim also emphasized that patients’ efforts should be accompanied by expert treatment.

He said, “As with all chronic diseases, it is important for the patient to manage rheumatoid arthritis so that the disease does not worsen.” I would like to recommend the production of vitamin D, which has an effect.”

Lastly, Professor Shim said, “Recently, it has been reported that there is a network between immune cells and nerve cells. Substances secreted from abnormally activated immune cells stimulate nerve cells to cause pain, and conversely, substances secreted from nerve cells The fact that it stimulates these immune cells was experimentally discovered,” he added. “Since stress actually increases pain, psychological stability is also important.”

The older you get, the less activity and muscle mass you need to reduce the amount of calories consumed, but the elderly are physiological. It is easy to accompany malnutrition because the amount of food is significantly reduced due to social factors. In addition, the need for certain individual nutrients, such as vitamins and minerals, can increase with aging, which can lead to nutritional imbalance.

Indeed, weight loss in the elderly is very common and is observed as a form of systemic wasting syndrome, or cachexia. In most cases, generalized wasting syndrome occurs following anorexia, and it is called “senile anorexia-kakexia” or “senile anorexia-general wasting syndrome”. Geriatric anorexia-cachexia or generalized wasting syndrome increases the morbidity and mortality of infectious diseases such as pneumonia and pressure sores in the elderly.

Senile systemic wasting syndrome is characterized by a decrease in the elderly’s ability to cope with external stressful situations such as infection, surgery, injury, and depression, which can easily progress to severe symptoms and is difficult to recover from.

Weight loss associated with malnutrition acts as a factor that exacerbates cognitive decline and depression, lowering quality of life and causing an increase in medical expenses. Unlike weight loss that accompanies simple starvation, weight loss in the form of wasting cachexia is characterized by very rapid loss of body protein, and most (70-80%) of weight loss is loss of lean body mass, mainly muscle mass.

Sarcopenia refers to a decrease in muscle and lean mass and is a result of geriatric general wasting syndrome or cachexia. Muscle strength, power, and endurance are all reduced, resulting in deterioration of the function of various organs. This means loss of physical function or vitality. ‘It goes through ‘failure to thrive’, and ultimately leads to frailty.

Treatment and prevention of malnutrition in the elderly

Inhibiting the chronic inflammatory response by increasing intestinal immunity along with balanced nutrient administration is an important approach for the treatment of geriatric anorexia-cachexia. Generalized wasting syndrome accompanied by geriatric anorexia does not cause weight gain simply by increasing caloric intake. In order to solve malnutrition, it is necessary to supply balanced nutrients including micronutrients, and in particular, to solve sarcopenia, the supply of protein is sufficient up to 1.5 times that of normal healthy adults. In addition to supplying nutrients, it is necessary to suppress the inflammatory response to reduce the body wasting response due to increased catabolism and promote appetite. While catabolism is suppressed, anabolic drugs or inflammatory cytokine inhibitors can be tried, and exercise can be combined to reduce age-related weight loss.

Cyproheptadine has problems with dizziness or sedation, but it is most commonly used as a first-line because it can down-regulate inflammatory cytokines to promote appetite and increase weight.

Megestrol acetate, used as an appetite stimulant for cancer patients, is effective in promoting appetite and preventing weight loss, so it is recommended to use it for a short period of about 2 weeks when necessary.

Omega-3 fatty acids are involved in cyclooxygenase and lipooxygenase metabolism and can contribute to promoting appetite by inhibiting inflammatory cytokine production and activity. Colostrum, which is rich in growth factors, contributes to the enhancement of immunity in the intestinal mucosa and reduces endotoxemia and bacteremia caused by intestinal bacteria, so it can be safely tried for the elderly. Glutamine is an amino acid that is important for immunity, protein metabolism, and maintenance of the intestinal mucosa.

In case of acute treatment of malnutrition related to severe disease, hospitalization and short-term intensive nutrition treatment focusing on intravenous nutrition are effective. However, oral nutritional supplement (ONS) is a very effective approach to preventing the occurrence of geriatric systemic wasting syndrome due to malnutrition or for elderly patients who have already developed it but do not require hospitalization. As a result of comparing the group that provided ONS once a day for a long period of time in a certain area with the group that did not provide ONS for the elderly who live daily life without actually being hospitalized, the result showed that not only the morbidity of the disease but also the number of hospitalizations due to the disease and the number of days of hospitalization decreased. could observe. Oral nutritional supplements are packaged in small quantities with improved taste of enteral nutrition preparations. Various preparations are being developed for taste, package size, calorie content, and for specific diseases. As it is based on enteral nutritional formulations, it contains the three major nutrients, such as protein, carbohydrates and fat, as well as micronutrients such as vitamins and minerals, in an appropriate ratio, making it suitable for nutritional supplementation. In principle, the intake method is to supplement 150 to 200 mL 1 to 3 times a day in the form of snacks avoiding meal times, but depending on the individual, the amount can be adjusted or some meals can be substituted. Most commercial products are classified as food, but Encover is listed as a drug, so doctors can prescribe it and health insurance applies. It is very useful both in terms of effectiveness and economically for the purpose of treatment and prevention of malnutrition for cancer patients or senile systemic wasting syndrome patients.

[Reference]
1) The Korean Society of Geriatrics: Geriatrics. 3rd
2) Am J Clin Nutr 2002;75:944-7.
3) Korean Journal of Intravenous Enteral Nutrition, 2013, Vol. 5, No. 2
4) Ageing Res Rev 2012 ;11(2):278-96.
5) AGE 2015;37: 81
6) Clin Nutr 2019;38(1):10-47
7) Nutrients 2021;13:835
8) J Frailty Aging 2022;11(2):129-134