Category: Drugs and Disease

23 September 2015
Food allergies are growing in prevalence in developed countries, and 3% of children globally are allergic to cow’s milk. New research carried out on children with cow’s milk allergy has shown that structural differences in gut bacteria may be the reason why some children do not acquire tolerance.

Teams from the University of Chicago, IL, Argonne National Laboratory in Lemont, IL, and the University of Naples Federico II in Italy found that some infants gained tolerance to cow’s milk after being treated with probiotic formula, while others did not.

The Centers for Disease Control and Prevention (CDC) name allergies as the sixth leading cause of chronic illness in the US, affecting more than 50 million Americans and costing more than $18 billion annually in health care. In a study released by the CDC in 2013, food allergies among children increased by 18% from 1997 to 2007 and by 50% between 1997 and 2011.

The National Institute of Allergy and Infectious Diseases note that allergy to cow’s milk is common in infants and young children and can develop within days to months after birth. Symptoms include abdominal pain, hives and eczema, or colic and sleeplessness, as well as blood in the stool and poor growth, depending on the type of immune response involved.

It seems increasingly likely that modern environmental influences, including widespread antibiotic use, high-fat and low-fiber diets, reduced exposure to infectious diseases, Cesarean birth and formula feeding are factors.

These are believed to have altered the mutually beneficial relationship between humans and the bacteria that live in the gastrointestinal tract. This dysbiosis, or distorting of the structure of the microbial community, can cause allergies in those who are genetically prone to developing them.

In previous research, Roberto Berni Canani and colleagues from the University of Naples studied the reaction of infants with cow’s milk allergy to probiotic and nonprobiotic formula. One group was given a formula containing a form of the milk protein casein, supplemented with the probiotic bacterial species Lactobacillus rhamnosus GG (LGG). The other group was treated with a nonprobiotic formula.
Those who took the probiotic formula developed a higher level of tolerance, suggesting that probiotic formula is more helpful in overcoming cow’s milk allergy.

Dr. Nagler and her team identified a common class of mucus-associated gut bacteria that are instrumental in regulating how dietary allergens reach the bloodstream. They now believe that the way commensal bacteria regulate allergic responses to food may be different than what was previously thought.

The findings suggest that certain bacteria make children more likely to develop tolerance, and that tolerance is linked to the acquisition of specific strains of bacteria, including Blautia and Coprococcus, which produce butyrate.

Jack Gilbert, PhD, associate professor in the Department of Ecology & Evolution at the University of Chicago, group leader for microbial ecology at Argonne National Laboratory and co-author of the study, says:

“The ability to identify bacterial strains that could be developed as a way to therapeutics for treating food allergies is a fundamental advance. Translating these findings into clinical treatments is our next goal.”

27 August 2015
A test that identifies genetic information in the blood picks up sensitive amounts of DNA that can be used to shape decisions about cancer treatment.

One of the challenges of modern medicine is to know if and when a cancer patient will relapse. A new study shows that months before tumors are visible on hospital scans, a “mutation-tracking” blood test can pick up valuable signs of a cancer’s return.

The study, undertaken by researchers at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust – both in the UK – is an important step toward changing the way cancer is monitored in the clinic and informing treatment decisions.

The clue to identifying a return of cancer cells is to look at circulating tumor DNA present in the blood. These are cancer cells left behind that may seed new tumors even after treatment.

By monitoring patients with blood tests taken after surgery, the study says, and then every 6 months in follow-up, the researchers were able to predict very accurately who would experience a relapse.

The study involved 55 women who had been successfully treated for early-stage breast cancer.
It was found those who tested positive for circulating tumor DNA were at 12 times greater risk of relapse compared with those who tested negative. In addition, the blood test was able to detect cancer recurrence an average of 7.9 months before any visible signs appeared.

Explaining what the researchers are attempting to achieve with the blood test, Kat Arney, science information manager at Cancer Research UK, told BBC Radio:

“They are looking for ways to detect DNA that has been shed by tumor cells into the bloodstream and saying can we use this DNA as a way of monitoring if the cancer is coming back – how it is changing, how it is evolving in the body – and then could we use that to monitor cancer and pick up potentially when it has come back without having to give scans or biopsies.”

“There are still challenges in implementing this technology […] but the information that it provides could make a real difference to breast cancer patients, ” added Dr. Nicholas Turner, team leader in molecular oncology at ICR and consultant medical oncologist at The Royal Marsden.
Findings could be applied to all breast cancer subtypes

Because the researchers were searching for mutations common to various breast cancer types, they found the test could be applied to all subtypes of the disease.

“This test could help us stay a step ahead of cancer by monitoring the way it is changing and picking treatments that exploit the weakness of the particular tumor, ” says Prof. Paul Workman, chief executive at ICR.

The potential of this new test, Arney told BBC Radio, is to “separate those mutations that are driving the cancer from all the other genetic chaos that is going on in there, looking at how we can target these particular gene faults in this particular person, and those are the same faulty genes that are driving their relapse when the cancer comes back.”

September 21, 2015

Patients with diabetic peripheral neuropathy who used a capsaicin 8% patch (Qutenza, Astellas Pharma) had more relief from pain and better sleep quality than those who received a placebo patch, according to a phase 3 study reported at the European Association for the Study of Diabetes (EASD) 2015 Meeting.

The results were presented as the company announced the patch has just been approved in Europe for the additional indication of the treatment of adult diabetes patients with peripheral neuropathic pain, either alone or in combination with other medicinal products for pain.

The capsaicin patch is already approved for use in the European Union for neuropathic pain, but that license excluded patients with diabetes. Similarly, in the United States, the capsaicin patch is approved for the treatment of postherpetic neuralgia, but this label doesn’t include diabetes patients.

At the EASD meeting, Malcolm Stoker, PhD, global medical lead at Astellas Pharma Global Development, the Netherlands, presented the findings of the randomized, placebo-controlled, double-blind STEP trial assessed the efficacy and safety of the patch, a dermal delivery system containing 8% capsaicin, vs placebo, following patients for 12 weeks

“We found that capsaicin 8% patch provides a statistically significant improvement in pain relief and sleep quality compared with placebo in these patients,” said Dr Stoker. The capsaicin patch “was well-tolerated, and safety was consistent with previous studies in postherpetic neuralgia and HIV-associated neuropathy.”

“The most commonly reported treatment-emergent adverse events were burning sensation [14% capsaicin, 2.7% placebo]; unsurprisingly, pain in extremity [10.8% vs 5.5%]; and application-site pain. There were no serious adverse events or deaths in either group,” Dr Stoker reported.

In conclusion, he added that the study extends the range of peripheral neuropathic pain etiologies for which the capsaicin 8% patch shows efficacy and safety.

August 18, 2015

After a long and controversial process, the US Food and Drug Administration (FDA) has approved the first-ever drug aimed at boosting female libido.

“Today’s approval provides women distressed by their low sexual desire with an approved treatment option,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, in a statement.

Flibanserin (Addyi) — also known as “Female Viagra” or “Pink Viagra” — will be marketed by Sprout Pharmaceuticals. It is approved to treat premenopausal women. The nonhormonal therapy — a 5-hydroxytryptophan (HT)(1A) receptor agonist and 5-HT(2A) receptor antagonist — was approved for hypoactive sexual desire disorder (HSDD). The HSDD diagnosis appeared in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-4), but was subsumed into a larger category of Female Sexual Interest/Arousal Disorder in the latest edition, DSM-5.

The once-daily 100-milligram tablet is to be taken at bedtime, and alcohol use will be contraindicated due to common side effects including drowsiness and dizziness. The label will include a boxed warning about the potential for increased hypotension or syncope with alcohol. The FDA is requiring Sprout to conduct three postmarketing studies in patients to better understand the interaction between flibanserin and alcohol. Concomitant use with moderate-to-strong CYP3A4 inhibitors — such as antifungals — will also be contraindicated and included in the boxed warning.

“HSDD is a very real problem for women,” Leah Millheiser, MD, director of the female sexual medical program at Stanford University School of Medicine, told Medscape Medical News. Dr Millheiser said that the condition is caused by an imbalance in neurotransmitters, and that “there is absolutely a need for a drug that’s been shown to be safe and effective.”

September 04, 2015
The Advisory Committee on Immunization Practices (ACIP) has revised its interval recommendations for the pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) in older healthy adults.

Specifically, immunocompetent adults older than 65 years who have not previously been vaccinated with pneumococcal vaccine should receive a dose of PCV13, followed at least 1 year later by a dose of PPSV23, according to the updated guidelines, published in the September 4 issue of the Morbidity and Mortality Weekly Report. If PPSV23 is given earlier than the recommended interval, the dose need not be repeated, the guidelines specify.

“No clinical studies evaluating efficacy of the two vaccines given in series are available. Therefore, current recommendations are based on best available evidence from immunogenicity studies,” the authors write.

In its previous guidelines published in 2014, the ACIP recommended routine use of a dose of PCV13 followed 6 to 12 months later by a dose of PPSV23. The change harmonizes the vaccine interval in this patient population with that recommended for immunocompetent adults older than 65 years who already received a dose of PPSV23. For adults in the latter group, the guidelines are unchanged: They should receive a dose of PCV13 at least 1 year after receiving the PPSV23, according to the report.

The revision is supported by studies of PCV–PPSV23 sequence among immunocompetent adults suggesting that shorter between-dose intervals may be associated with increased local reactogenicity when compared with longer intervals, whereas intervals of at least 1 year may lead to an improved immune response against serotypes in both vaccines compared with a single dose of either, the authors write.

The vaccine interval recommendations for other patient populations remain unchanged from the existing guidelines. In particular, a dose of PPSV23 should be given at least 8 weeks after a dose of PCV13 in children and adults at high risk for pneumococcal disease, including those with an immunocompromising condition, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant.

“The currently recommended 8-week interval minimizes the risk window for invasive pneumococcal disease caused by serotypes unique to PPSV23 in these highly vulnerable groups,” the authors write.

Children with an immunocompromising condition or functional or anatomic asplenia should receive a second dose of PPSV23 5 years after the first PPSV23, according to the guidelines.

August 28, 2015
Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes may cause joint pain so intense it is disabling, the US Food and Drug Administration (FDA) warned today.

Fortunately, the pain goes away, usually in less than a month, once patients stop taking the medicine.

The agency said it identified 33 cases of severe arthralgia associated with DPP-4 inhibitors from October 16, 2006, through December 31, 2013, in its FDA Adverse Event Reporting System database. Twenty-eight of the cases involved sitagliptin (Januvia, Merck & Co, Inc). Sitagliptin accounts for more than 80% of all DPP-4 prescriptions in the country, according to a spokesperson for Merck.

Patients began experiencing joint pain anywhere from 1 day to years after they started taking the drugs. For 10 patients, disabling pain required hospitalization.

Clinicians prescribe DPP-4 inhibitors in conjunction with diet and exercise to reduce blood sugar levels in patients with type 2 diabetes. They are either combined with other diabetes drugs such as metformin or dispensed as stand-alone products.

The US Food and Drug Administration (FDA) yesterday approved a topical gel combination of adapalene 0.3% and benzoyl peroxide 2.5% (Epiduo Forte, Galderma) for the treatment of acne vulgaris, the company has announced.

The approval was based on a phase 3 randomized double-blind study involving 217 patients, all aged 12 years and older, with an average patient age of 20 years. In the study, Epiduo Forte gel was superior to vehicle control gel in the overall study population of patients with moderate to severe acne at week 12 for the Investigator’s Global Assessment Success Rate and for changes in inflammatory and noninflammatory lesion count, the company notes in a news release announcing the approval.

In addition, half of the patients had severe acne at baseline, and more than half of this group (50.5%) saw marked improvement during the study, with results seen as early as 1 week, with continued improvement through week 12, according to the company.

“Acne is a challenging condition to manage. It can vary greatly from patient to patient, can have a significant physical and psychosocial impact on sufferers, and patients can find treatment adherence difficult to maintain,” Jonathan Weiss, MD, a board-certified dermatologist at Gwinnett Dermatology, PC, and lead investigator on the study, said in the news release.

“For many patients, rapid results are especially important, and some acne treatments take time to show effect. We were very excited to see in the clinical trial that people using Epiduo Forte gel saw results as early as 1 week, with efficacy continually improving through week 12,” Dr Weiss added.

Erythema, scaling, dryness, stinging/burning, and irritant and allergic contact dermatitis may occur with Epiduo Forte, requiring discontinuation in some cases.

Patients using Epiduo Forte gel should avoid exposure to sunlight and sunlamps and wear sunscreen when sun exposure cannot be avoided, the company said.

Epiduo Forte gel will be available by prescription beginning in September.

The formulation of adapalene 0.1% and benzoyl peroxide 2.5% (Epiduo) was approved by the FDA in 2009 for use in patients 12 and older.

The U.S. Food and Drug Administration today approved Entresto (sacubitril/valsartan) tablets for the treatment of heart failure. The drug has been shown to reduce the rate of cardiovascular death and hospitalization related to heart failure.

Entresto was studied in a clinical trial of more than 8,000 adults and was shown to reduce the rate of cardiovascular death and hospitalizations related to heart failure compared to another drug, enalapril. Most patients were also receiving currently approved heart failure treatments, including beta-blockers, diuretics, and mineralocorticoid antagonists.

The most common side effects in clinical trial participants being treated with Entresto were low blood pressure (hypotension), high blood potassium levels (hyperkalemia), and poor function of the kidneys (renal impairment).

Angioedema (an allergic reaction usually appearing as swelling of the lips or face) was also reported with Entresto; black patients and patients with a prior history of angioedema have a higher risk. Patients should be advised to get emergency medical help right away if they have symptoms of angioedema or trouble breathing while on Entresto. Health care professionals should advise patients not to use Entresto with any drug from the angiotensin converting enzyme (ACE) inhibitor class because the risk of angioedema is increased. When switching between Entresto and an ACE inhibitor, use of the two drugs should be separated by 36 hours.

Health care professionals should counsel patients about the risk of harm to an unborn baby. If pregnancy is detected, use of Entresto should be discontinued as soon as possible.