New Drug Shows Promise Against Tough-to-Manage Asthma

Dennis Thompson wrote . . . . . . . . .

An experimental injectable drug appears more versatile than existing medications in treating people with different forms of severe, hard-to-control asthma, clinical trial results show.

There are many different types of asthma brought on by many different triggers, and a number of monoclonal antibody medications — called “biologics” — have been crafted to target distinct asthma triggers.

This new drug, tezepelumab, is yet another monoclonal antibody, but it targets an inflammatory protein thought to play an early role in many different types of asthma, said researcher Dr. Andrew Menzies-Gow, director of the lung division at Royal Brompton Hospital in London, England.

A phase 3 clinical trial found that tezepelumab is effective in quelling severe asthma among patients who had widely varying causes of their shortness of breath, according to a report published May 13 in the New England Journal of Medicine. Phase 3 is the final stage required for U.S. Food and Drug Administration approval.

“Managing severe asthma is challenging, with multiple inflammatory pathways often contributing to the complexity of a patient’s disease,” Menzies-Gow said. He added that the results of this clinical trial “underscore the potential of tezepelumab to transform treatment for a broad population of severe asthma patients, regardless of their type of inflammation.”

For example, patients benefited from the drug whether or not they suffer seasonal allergies, the results showed.

Asthma is a common lung problem. Between 5% and 10% of people with asthma suffer from severe symptoms and frequent asthma attacks even though they are on the maximum available treatment, Menzies-Gow said.

Tezepelumab blocks a protein called thymic stromal lymphopoietin (TSLP) that promotes multiple inflammatory processes that have all been linked to asthma attacks, the study authors said in background notes.

The researchers tested tezepelumab in more than 1,000 people, with about half randomly assigned to receive an inactive placebo and the other half receiving monthly 210 mg injections of the drug.

The trial participants were chosen to reflect the different causes of severe asthma. For example, about half had elevated levels of eosinophil, a type of white blood cell that promotes swelling throughout the entire respiratory system rather than just the airways.

Dr. James Li, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., who was not involved with the research, said, “In this particular study, the subjects had to have had two asthma exacerbations in the previous 12 months — so, uncontrolled asthma. It’s for the worst cases, so to speak.”

After a year’s treatment, patients on tezepelumab experienced fewer asthma attacks and better lung function, asthma control, and health-related quality of life than those on placebo, the researchers reported.

Further, the patients improved regardless of the specific problem causing their asthma:

People with a low eosinophil count had a 41% reduced rate of asthma attacks, while those with a high count had a 70% reduction.
People affected by seasonal allergies had a 58% reduction in asthma attacks, while asthmatics not sensitive to allergens had a 51% reduction.
“The current biologic treatments that we have are used in subsets of severe asthma,” Li said. “This particular medication showed effectiveness regardless of eosinophil count or allergy status.”

This drug will add to the arsenal of biologic drugs available to treat people with severe asthma, said Dr. Richard Lockey, an allergy specialist in Tampa, Fla., and past president of the World Allergy Organization.

“Most of the drugs that we already have available show this kind of efficacy, but this may interfere with more inflammatory pathways,” Lockey said, saying it could prove the first choice in treating some forms of asthma and a back-up option for others.

Tezepelumab also proved safe, with no significant side effects, the experts noted.

The FDA granted tezepelumab its Breakthrough Therapy Designation in 2018, which is intended to expedite the development and regulatory review of promising new drugs.

Source: HealthDay

Opioids After Dental Work May Be Dangerous

Getting a prescription for an opioid painkiller from your dentist could put you or your family at risk for an overdose, a new study warns.

The finding is based on an analysis of data from 8.5 million Americans who had teeth pulled or 119 other types of dental work between 2011 and 2018. All had Medicaid or private dental insurance.

“Our paper shows that when patients fill dental opioid prescriptions, the risk of opioid overdose increases both for themselves and their family members,” said study leader Dr. Kao-Ping Chua of the University of Michigan, in Ann Arbor.

“This underscores the importance of avoiding dental opioid prescribing when non-opioids like ibuprofen [Motrin] and acetaminophen [Tylenol] are effective options for pain control, as is the case for the majority of dental procedures,” Chua added in a university news release.

Nonetheless, nearly 27% of teens and adults filled a prescription for an opioid painkiller, such as hydrocodone or oxycodone, and 2,700 opioid overdoses occurred within 90 days of the dental procedures, the study found.

The overall rate of opioid overdoses was about three for every 10,000 dental procedures, according to the report. But the rate was 2.5 times higher among patients who filled an opioid prescription within three days of their procedure than among those who did not (5.8 versus 2.2 per 10,000).

In 2016 alone, U.S. dentists wrote 11.4 million opioid prescriptions, so the findings suggest that 1,700 overdoses a year could be associated with dental opioid prescriptions, the study authors said.

Family members of dental patients who receive opioid prescriptions are also at risk for overdoses, the findings showed.

The researchers examined data from 3.5 million privately insured dental patients and found that 400 of their family members were treated for opioid overdoses in the 90 days after the patient’s procedure.

The rate was 1.7 per 10,000 procedures among family members of privately insured patients who filled opioid prescriptions, compared with 1 per 10,000 procedures among those who did not. Patients’ children accounted for 42% of the family overdoses, spouses for 25%, and the rest occurred in siblings and parents.

“Our finding of increased overdose risk in family members also shows the importance of emphasizing safe storage and disposal when prescribing opioids to dental patients,” said Chua, a pediatrician at Michigan Medicine and health care researcher at the Susan B. Meister Child Health Evaluation Research Center in Ann Arbor.

Senior study author Dr. Romesh Nalliah, associate dean for patient services at the University of Michigan School of Dentistry, said this is one of the most powerful truths the team unlocked in their “big data” study of dental opioid prescribing. “That when a dentist, like me, prescribes an opioid to a patient I am putting their entire family at risk of overdose,” he said. “Dentists should consider, if the family concerned was yours, would you take that risk?”

The study was published online in the American Journal of Preventive Medicine.

Source: HealthDay

New Drug May Be Better Psoriasis Treatment

Dennis Thompson wrote . . . . . . . . .

A breakthrough psoriasis drug is better at treating the itchy and painful skin disease than medicines already on the market, according to results from two clinical trials.

There was a “night and day difference” in the results from bimekizumab compared against two established psoriasis drugs, secukinumab (Cosentyx) and adalimumab (Humira), said Dr. Mark Lebwohl, a co-researcher in one of the clinical trials.

“We’ve never had a drug which in its phase 3 trials had more than 50% of patients achieve” a 100% reduction in their psoriasis symptoms, said Lebwohl, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai in New York City.

“We’re now at a point where we can clear the vast majority of psoriasis patients with medications that are very effective and very safe,” he added.

Based on these results, Lebwohl expects the Belgian pharmaceutical company UCB Pharma to pursue quick approval of bimekizumab with the U.S. Food and Drug Administration.

“I would hope it would be on the market this summer,” he said.

Psoriasis affects more than 8 million people in the United States, according to the National Psoriasis Foundation.

It’s an autoimmune disease that speeds up skin cell growth, causing cells to pile up on the surface of the skin and form plaques that itch, burn and sting. These plaques can appear on any part of the body, but are most often found on the elbows, knees and scalp.

A pro-inflammatory biochemical called interleukin-17 (IL-17) has been implicated in the development of psoriasis, Lebwohl said. Secukinumab and adalimumab work by blocking the chemical’s most potent form, called IL-17A.

Bimekizumab blocks both IL-17A and another form of the chemical called IL-17F, Lebwohl said. The injectable drug is administered once a month.

“The biology [of the two forms of IL-17] is overlapping — 17A is more potent but 17F is more abundant,” Lebwohl said. “Even though 17A is stronger at causing psoriasis, there is more of 17F. By blocking both, you get the full effect.”

After 48 weeks of treatment, about 67% of bimekizumab patients had complete clearing of their psoriasis plaques, compared with 46% of patients receiving secukinumab, according to results of the trial that Lebwohl co-authored. A total 743 patients participated.

The other clinical trial, involving 478 patients, offered similar results. After 16 weeks, 86% of patients on bimekizumab had experienced a 90% reduction in their psoriasis plaques, nearly double the 47% who achieved the same response with adalimumab.

“They block IL-17A, while this blocks both IL-17A and IL-17F,” Lebwohl said. “That’s probably why it’s so effective. Blocking that extra little bit of IL-17 actually gets you the added effectiveness.”

Bimekizumab also has been shown to effectively treat psoriatic arthritis, a condition that affects 1 in 3 people with psoriasis, Lebwohl said.

People taking bimekizumab were four to 10 times more likely to have a reduction in their arthritis symptoms than a placebo group, with the response growing with the size of the dose, according to results published in The Lancet.

Blocking IL-17 does cause a greater risk of yeast infections, and the risk is stronger with bimekizumab than the other two drugs, results showed.

“Nature has done an experiment for us by giving us people who are deficient in IL-17, and they get awful yeast infections,” Lebwohl said. “We anticipated before the study is that the only side effect we’d see was yeast infections, and that’s what happened.”

The mild to moderate cases of yeast infection that occurred in the clinical trials were “easily treated with fluconazole,” an oral anti-fungal drug, Lebwohl said.

Dr. Michele Green, a dermatologist with Lenox Hill Hospital in New York City, reviewed the findings.

“This is an impressive study showing significant results using an interleukin-17 inhibitor to treat plaque psoriasis,” she said.

However, Green sounded a note of caution, urging further study of the drug.

“A larger sample size needs to be used since in addition to candidiasis, interleukin inhibitors have been associated with higher rates of other opportunistic infections, severe infections and cancer,” Green said.

The clinical trial results were published in the New England Journal of Medicine, and also were presented at an online meeting of the American Academy of Dermatology.

Source: HealthDay

Anti-aging Compound Improves Muscle Glucose Metabolism

Jim Dryden wrote . . . . . . . . .

In the first clinical trial of nicotinamide mononucleotide (NMN), researchers at Washington University School of Medicine in St. Louis have found that the compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice also has clinically relevant effects in people.

A natural compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice has clinically relevant effects in people, according to new research at Washington University School of Medicine in St. Louis.

A small clinical trial of postmenopausal women with prediabetes shows that the compound NMN (nicotinamide mononucleotide) improved the ability of insulin to increase glucose uptake in skeletal muscle, which often is abnormal in people with obesity, prediabetes or Type 2 diabetes. NMN also improved expression of genes that are involved in muscle structure and remodeling. However, the treatment did not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as seen in mice.

The study, published online in the journal Science, is the first randomized clinical trial to look at the metabolic effects of NMN administration in people.

Among the women in the study, 13 received 250 mg of NMN orally every day for 10 weeks, and 12 were given an inactive placebo every day over the same period.

“Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said senior investigator Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvements in other markers of metabolic health, which we did not detect in our study participants.”

The remarkable beneficial effects of NMN in rodents have led several companies in Japan, China and in the U.S. to market the compound as a dietary supplement or a neutraceutical. The U.S. Food and Drug Administration is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, and many people in the U.S. and around the world now take NMN despite the lack of evidence to show clinical benefits in people.

The researchers studied 25 postmenopausal women who had prediabetes, meaning they had higher than normal blood sugar levels, but the levels were not high enough to be diagnosed as having diabetes. Women were enrolled in this trial because mouse studies showed NMN had the greatest effects in female mice.

NMN is involved in producing an important compound in all cells, called nicotinamide adenine dinucleotide (NAD). NAD plays a vital role in keeping animals healthy. Levels of NAD decline with age in a broad range of animals, including humans, and the compound has been shown to contribute to a variety of aging-associated problems, including insulin resistance in studies conducted in mice. Supplementing animals with NMN slows and ameliorates age-related decline in the function of many tissues in the body.

Co-investigator Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine who has been studying NMN for almost two decades and first reported on its benefits in mice said, “This is one step toward the development of an anti-aging intervention, though more research is needed to fully understand the cellular mechanisms responsible for the effects observed in skeletal muscle in people.”

Insulin enhances glucose uptake and storage in muscle, so people who are resistant to insulin are at increased risk for developing Type 2 diabetes. But the researchers caution that more studies are needed to determine whether NMN has beneficial effects in the prevention or management of prediabetes or diabetes in people. Klein and Imai are continuing to evaluate NMN in another trial involving men as well as women.

Source: Washington University in St. Louis

Doctors’ Group Says Antibiotics Can Be Taken for Shorter Periods

Amy Norton wrote . . . . . . . . .

Millions of Americans have at some point in their lives gotten a long course of antibiotics to treat a bacterial infection. But according to new recommendations from a major U.S. doctors’ group, some of the most common bacterial infections can now be treated with shorter courses of the drugs.

The advice, from the American College of Physicians (ACP), says that for several types of infections, shorter courses of antibiotics do the job — and even do it more safely.

The conditions include straightforward cases of pneumonia, skin infection and urinary tract infection (UTI), meaning they are not complicated by other medical conditions.

In general, the ACP says, they can be managed with five to seven days of antibiotics, or even three days in certain cases, instead of the traditional 10 days or more.

Many patients are accustomed to long courses, but their use was largely based on “conventional wisdom,” said ACP president Dr. Jacqueline Fincher.

In recent years, she said, clinical trials have shown that shorter courses are just as effective at “eradicating” many infections.

It’s a safer approach, too, Fincher explained: Shorter courses lessen the chance of side effects like nausea and diarrhea. They may also help battle the widespread problem of antibiotic resistance — where bacteria that are exposed to an antibiotic mutate in an attempt to thwart the drug.

Antibiotics, especially long courses, can also kill “good” bacteria that normally dwell in the body and help keep its various systems running smoothly, Fincher said.

Yeast infections, she noted, are one example of how that balance can be upset: When women take an antibiotic for a UTI, that can diminish the good bacteria that normally keep yeast growth in check.

One particular concern, Fincher said, are potentially fatal gut infections caused by antibiotic-resistant C. difficile bacteria. Those infections often arise after a person has had antibiotic treatment that destroyed many of the good bacteria in the gut.

The new ACP recommendations advise shorter antibiotic courses for four groups of infection:

  • Acute bronchitis in people with chronic obstructive pulmonary disease. COPD is an umbrella term for two serious lung conditions: emphysema and chronic bronchitis. When COPD patients develop worsening symptoms (acute bronchitis) and the cause is likely a bacterial infection, the ACP advises antibiotic treatment for a maximum of five days. (In previous advice, the ACP has said that people without COPD do not need antibiotics for acute bronchitis — unless they may have pneumonia.)
  • Pneumonia. When people develop uncomplicated pneumonia, antibiotics should be given for a minimum of five days, and possibly longer depending on symptoms.
  • UTIs. Treatment can often be five to seven days, or even shorter. Women may be able to take the antibiotic combination trimethoprim-sulfamethoxazole for three days, or a newer antibiotic called fosfomycin as a single dose.
  • Cellulitis. This is a common skin infection that often affects the limbs. As long as the infection does not involve pus (such as an abscess), it can be treated with antibiotics for five to six days.

Fincher said the advice focused on those four groups, in part, because they are so common. But shorter courses could also be appropriate for other less serious infections, she added.

Some conditions will still need longer courses, Fincher said — including “deep” infections like osteomyelitis, where there is inflammation of the bone. Longer treatment may also be better for certain patients, like those with diabetes or compromised immune systems, she noted.

“Antibiotics can be lifesaving, but like any medication, they have side effects,” said Dr. Helen Boucher, a member of the Infectious Diseases Society of America’s Board of Directors.

First, it’s important for patients to be sure they really need an antibiotic, said Boucher, who also heads the infectious diseases division at Tufts Medical Center in Boston.

An estimated 30% of antibiotic prescriptions in the United States are unnecessary, she noted.

“Ask your doctor, ‘Do I really need this?'” Boucher advised. The next question, she said, can be about duration: If the prescription is for 10 days — the “default” for many doctors, the ACP says — patients can again ask why.

Why are shorter courses being advocated now? It was only in recent years that clinical trials began testing shorter versus longer antibiotic treatment, Boucher explained. (Drug companies do not have much incentive to study less treatment, she noted.)

It was the problem of antibiotic resistance, Boucher said, that spurred researchers to see whether shorter courses could be just as effective.

The recommendations were published in the ACP journal Annals of Internal Medicine.

Source: HealthDay