Scientists Spot Unexpected Player in Fibromyalgia

Fibromyalgia is a mysterious and misunderstood illness, but researchers may have uncovered at least one key to the disease’s origin: insulin resistance.

The new research compared a small group of people with fibromyalgia to two groups of healthy people and noted that a long-term measure of blood sugar levels was higher in the people with fibromyalgia. Insulin resistance develops when the body starts to struggle with breaking down sugar.

To see if treating those higher blood sugar levels might help, the researchers gave people who had blood sugar levels in the pre-diabetic range or higher a diabetes medication called metformin. People taking metformin reported significantly lower pain scores, according to the study.

“We combined metformin with standard drugs used for fibromyalgia and saw a much greater degree of pain relief,” said study author Dr. Miguel Pappolla. He is a professor of neurology at the University of Texas Medical Branch at Galveston.

In fact, Pappolla said, the additional pain relief was so significant that the researchers actually called patients on different days to re-check their pain scores.

Because this is a preliminary finding, the researchers aren’t sure how insulin resistance might contribute to fibromyalgia or how metformin might reduce pain. “Metformin may have some analgesic [pain-relieving] activity on its own,” Pappolla said.

Fibromyalgia is a condition that causes widespread pain, fatigue, sleep problems and distress, according to the U.S. Centers for Disease Control and Prevention. Even celebrities aren’t spared from this painful condition — Lady Gaga reportedly had to cancel concerts on her tour due to pain from fibromyalgia.

Though the cause of the disorder isn’t clear, it appears that people with fibromyalgia may be more sensitive to pain than other people — what the CDC calls abnormal pain processing.

Pappolla said that studies have shown differences in the brain between people with fibromyalgia and those without, such as areas with a lower blood flow than expected. The researchers noted that similar problems have been seen in people with diabetes.

The study included 23 people with fibromyalgia. The researchers compared their hemoglobin A1c levels to large groups of healthy people from two other studies. Hemoglobin A1c is a simple blood test that measures what someone’s blood sugar levels were during the past two or three months. A level of 5.7% to 6.4% is considered pre-diabetes, according to the American Diabetes Association. A level of 6.5% or higher means a person has diabetes.

Only six of those with fibromyalgia had normal blood sugar levels. Sixteen had levels considered pre-diabetes and one met the criteria for diabetes.

When the researchers compared the average blood sugar levels of the fibromyalgia group to healthy age-matched people in the other studies, they saw that the blood sugar levels were higher in the people with fibromyalgia, suggesting insulin resistance.

The findings were published online recently in the journal PLOS ONE.

Dr. Edward Rubin, an anesthesiologist and pain management specialist at Long Island Jewish Medical Center, said, “It’s interesting that there’s a possible connection between fibromyalgia and blood sugar. We’ve been attacking the symptoms of fibromyalgia, but we don’t have a good understanding of the root cause of fibromyalgia.”

Rubin, who wasn’t involved in the study, said there may be enough evidence here to try metformin along with other medications used for fibromyalgia for people whose blood sugar levels fall outside of the normal range, to see if they have a positive response.

Dr. Bharat Kumar, from the University of Iowa Hospitals and Clinics, said this study shows people with the disease that there is hope.

“People with fibromyalgia are often told [falsely] that they have a disease that simply cannot be managed. This article shows that it’s not true. Although it’s unclear if metformin will work for every person suffering from fibromyalgia, there is active research into finding solutions for this frustrating and overlooked condition,” he said.

Kumar said it’s biologically plausible that insulin could have an effect on pain. “We know that other hormone abnormalities can cause fibromyalgia-like symptoms, so [this finding] is not too surprising,” he added.

Still, he said, he didn’t expect that metformin would be a “silver bullet” for all fibromyalgia pain. He said there are likely a number of causes of the disease.

More information

Learn more about fibromyalgia from the American College of Rheumatology.

https://www.usnews.com/news/health-news/articles/2019-05-16/scientists-spot-unexpected-player-in-fibromyalgia

ADA Standards Updated With Renal Guidance Based on CREDENCE

The American Diabetes Association (ADA) has updated its “living” Standards of Medical Care in Diabetes to incorporate findings from the Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (CREDENCE) trial, including revised renal management guidelines.

The updates, from the ADA’s Professional Practice Committee, are published in sections 10 (Cardiovascular Disease and Risk Management) and 11 (Microvascular Complications and Foot Care) of the association’s online Standards.

The specific changes are detailed on a separate page.

In CREDENCE, which enrolled 4401 patients with type 2 diabetes and chronic kidney disease (CKD), canagliflozin (Invokana, Janssen), a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, lowered the risk for progression to end-stage renal disease (ESRD) by 30%, and was also associated with significantly lower rates of major cardiovascular events, including death and hospitalization for heart failure. In addition, risk of the renal-specific composite outcome of ESRD, doubling of serum creatinine, and death from renal causes was lowered by 34% in the canagliflozin group compared with placebo.

The main CREDENCE results, hailed as ground-breaking, were reported in April at the International Society of Nephrology 2019 World Congress and simultaneously published in the New England Journal of Medicine.

The trial, which was launched in 2014, was stopped nearly a year earlier than planned because it met its prespecified efficacy endpoints.

Importantly, notes ADA, “the renal and cardiovascular risk reduction observed in CREDENCE was present in patients with an eGFR in the 30-45 mL/min/1.73m² range.”

And “although the adverse event profiles of these agents must be considered, the risk-benefit balance of SGLT2 inhibitor treatment appears to be favorable for most patients with type 2 diabetes and CKD,” it adds.

“No increased risk of lower-limb amputations, fractures, acute kidney injury, or hyperkalemia were noted for canagliflozin relative to placebo in CREDENCE. An increased risk for diabetic ketoacidosis was noted, however, with 2.2 and 0.2 events per 1000 patient-years noted in the canagliflozin and placebo groups, respectively.”

Updated Renal Management Guidelines

Based on the CREDENCE results, ADA now recommends as part of section 11 (Microvascular Complications and Foot Care):

• 11.1 At least once a year, assess urinary albumin (eg, spot urinary albumin-to-creatine ratio) and estimated glomerular filtration (eGFR) rate in patients with type 1 diabetes with duration of ≥ 5 years; in all patients with type 2 diabetes, regardless of treatment; and in all patients with comorbid hypertension. Grade of evidence: B
• 11.3 For patients with type 2 diabetes and diabetic kidney disease, consider use of an SGLT2 inhibitor in patients with an eGFR ≥ 30 mL/min/1.73m² and particularly in those with > 300 mg/g albuminuria to reduce risk of CKD progression, cardiovascular events, or both. Grade of evidence: A
• In patients with CKD who are at increased risk for cardiovascular events, use of a glucagon-like peptide 1 (GLP-1) receptor agonist may reduce risk of progression of albuminuria, cardiovascular events, or both. Grade of evidence: C

Section 11.8 (continued monitoring of urinary albumin-to-creatinine ratio in patients with albuminuria treated with an ACE inhibitor or an angiotensin receptor blocker is reasonable to assess the response to treatment and progression of CKD) has been removed.

CREDENCE Information Added to CVD Section

In section 10 (Cardiovascular Disease and Risk Management), information about CREDENCE has been added to the third paragraph of the subsection “Antihyperglycemic Therapies and Cardiovascular Outcomes.”

The updated section also summarizes data from the Canagliflozin Cardiovascular Assessment Study (CANVAS) and CANVAS renal endpoints trial (CANVAS-R), which were presented together at the American Diabetes Association (ADA) 2017 Scientific Sessions and simultaneously published in the New England Journal of Medicine (2017;377:644-657).

In CANVAS, canagliflozin reduced cardiovascular events by 14% and cut the rate of renal function decline by 40% but also doubled the risk for lower-limb amputation (6.3 vs 3.4 cases/1000 patient-years; hazard ratio, 1.97).

Information about CREDENCE is now also incorporated into the fourth paragraph of the subsection “Antihyperglycemic Therapies and Heart Failure” in section 10, noting that the risks for heart failure hospitalizations were reduced by 39% and the composite of cardiovascular death or heart failure hospitalization by 31% with canagliflozin.

The changes to section 10 have also been endorsed by the American College of Cardiology.

https://www.medscape.com/viewarticle/913868

D2d: Vitamin D Doesn’t Stop Diabetes in Those With Prediabetes

Vitamin D3 supplementation in people at high risk of developing diabetes but who did not have vitamin D insufficiency does not reduce the chances of developing the disease compared with placebo, the new results of a randomized, placebo-controlled trial show.

The findings from the Vitamin D and Type 2 Diabetes (D2d) trial were presented here at the American Diabetes Association 2019 Scientific Sessions by Anastassios Pittas, MD, from Tufts Medical Center, Boston, Massachusetts.

“Our study results did not show a statistically significant benefit for vitamin D in decreasing progression to type 2 diabetes in people who have sufficient levels,” he said.

However, he added that “in a post-hoc analysis we did see that vitamin D supplementation potentially had a benefit in those with very low vitamin D levels (20% of the study population was deemed at least vitamin D ‘insufficient’ as opposed to the remainder who were vitamin D sufficient).”

After 2.5 years of follow-up of over 99% of the participants, no significant difference was found in the development of diabetes between those taking vitamin D supplementation and those on placebo (P = .12).

The study was simultaneously published in the New England Journal of Medicine, along with an editorial by Deborah J. Wexler, MD, from Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston.

Wexler notes that D2d “is the largest” of a number of randomized controlled trials looking at vitamin D supplementation to prevent progression to type 2 diabetes and, as such, these results are “long-awaited.”

But she points out that the findings show that “Any benefit of vitamin D for diabetes prevention, if present, is modest and clearly does not pertain to a vitamin D-sufficient population.”

“Whether targeting populations with vitamin D levels below 12 ng/mL, many of whom have additional risk factors for diabetes, would have an effect on beta-cell function and progression to type 2 diabetes remains unresolved.”

Trial Participants Had Prediabetes but Most Were Not Vitamin D Insufficient

The D2d multicenter trial aimed to test whether vitamin D supplementation reduces the risk of the development of type 2 diabetes among adults at high risk for the disease, ie, those with prediabetes.

The authors note the biological plausibility of vitamin D status influencing risk for type 2 diabetes, highlighting that “both impaired pancreatic beta-cell function and insulin resistance have been reported with low blood [levels] of 25-hydroxyvitamin D.”

They add that observational studies suggest a low blood vitamin D level is associated with diabetes risk, and this is further supported by mechanistic studies showing that vitamin D supplementation improved pancreatic beta-cell function by 40%.

In the study, a total of 2423 participants across 22 US cities were randomized (1211 to the vitamin D group and 1212 to the placebo group) to receive 4000 IU/day of vitamin D or placebo, regardless of baseline serum 25-hydroxyvitamin D level.

The 4000 IU/day dose was selected to balance safety and efficacy and resulted in a large difference in the serum 25-hydroxyvitamin D level between the trial groups in the first 2 years of follow-up.

Participants were required to meet at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100-125 mg/dL; plasma glucose level 2 hours after a 75-g oral glucose load, 140-199 mg/dL; and HbA_1c, 5.7%-6.4%) with no diagnostic criteria for diabetes.

Researchers specifically designed D2d to include participants at high risk for type 2 diabetes regardless of their vitamin D level.

When the study began, just under 80% of participants had vitamin D levels considered sufficient by US nutritional standards (≥ 20 ng/mL).

A further 17.4% had levels between 12 and 19 ng/mL, so they were not deficient but did not have sufficient levels, while 4.3% of the overall trial participants were vitamin D “deficient” (< 12 ng/mL).

Women comprised 44.8% of participants, mean age was 60 years, and mean BMI was 32.1 kg/m²; 33.3% were nonwhite and 9.3% were Hispanic. Participants had a mean HbA_1c of 5.9% (48 mmol/mol).

Participants were followed for new-onset diabetes, with blood tests performed every 6 months for a median of 2.5 years.

The primary outcome was a diagnosis of new-onset diabetes, based on annual glycemic testing of fasting plasma glucose, HbA_1c, and 2-hour postload plasma glucose, and semi-annual testing of fasting plasma glucose and HbA_1c.

After 2.5 years of follow-up, new-onset diabetes had developed in 293 participants in the vitamin D group and 323 patients in the placebo group (9.4 events and 10.7 events/100 person-years, respectively), Pittas reported.

So no significant difference was found in the development of diabetes between those taking vitamin D supplementation and those taking placebo (hazard ratio [HR], 0.88; 95% CI, 0.75 – 1.04; P = .12).

By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng/mL (from 27.7 ng/mL at baseline) compared with 28.8 ng/mL in the placebo group (from 28.2 ng/mL at baseline).

The incidence of adverse events did not differ significantly between the two groups, including hypercalcemia, a fasting urine calcium–creatinine ratio of more than 0.375, a low estimated glomerular filtration (eGFR) rate, and nephrolithiasis.

In the vitamin D supplementation group, 135 participants discontinued their pills, 15 started a diabetes medication, and seven started a weight-loss medication. compared with 107, 19 and 10 participants, respectively, in the placebo group.

“We did a per-protocol exploratory analysis to see if, by excluding patients who started medications or took out-of-trial vitamin D supplements above the trial limit of 1000 IU/day, made a difference.”

“We found that the primary outcome occurred in 22.0% in the vitamin D group and 25.1% in the placebo group with an HR of 0.84 [95% CI, 0.71 – 1.00],” Pittas explained.

Finally, Pittas noted that in the US population “the proportion of people with vitamin D insufficiency has improved over recent years; however, the proportion with vitamin D deficiency has remained stable, paving the way for further research with existing data.”

Effect of Vitamin D Supplementation in Those With Deficiency Unknown

In her editorial, Wexler remarks that the observed HR of 0.88 for the primary endpoint of the trial does not rule out a modest benefit of vitamin D. A larger and longer trial might be necessary to show a significant benefit in a vitamin D-sufficient population, she explains.

Wexler goes on to say that the effect might be greater if vitamin D supplementation was given to people who truly have a vitamin D deficiency, in comparison to participants in the D2d trial who largely did not.

In the US, “correlates of vitamin D insufficiency include older age, black, Asian or Hispanic race, and obesity,” among other factors.

“Indeed, in the D2d trial, a post hoc analysis of data from the 103 participants with vitamin D deficiency (< 12 ng/mL) showed an HR for [new-onset] diabetes with vitamin D supplementation of 0.38 (95% CI, 0.18 – 0.80),” compared with placebo, she stresses.

But Wexler adds that, overall, in a prespecified subgroup analysis of those who did not have sufficient levels, “the HR in participants with a level [of vitamin D] < 20 ng/mL was essentially the same as that in participants with a ‘sufficient’ level of ≥ 20 ng/mL or higher (0.87 and 0.89, respectively).”

Pittas noted that other large trials from Japan, the United States, and Norway have shown similar HRs to the D2d trial with a range of 0.87 to 0.9.

ADA 2019 Scientific Sessions. Presented June 7, 2019. N Engl J Med. Published online June 7, 2019. Abstract

Pittas has disclosed no relevant financial relationships. Wexler has sat on the data monitoring committee for oral semaglutide, Novo Nordisk. 

https://www.medscape.com/viewarticle/914136#vp_1

Amarin to Present on Reducing Cardiovascular Risks in Diabetes

Amarin Corporation plc (NASDAQ: AMRN), a pharmaceutical company focused on improving cardiovascular health, today announced that three Amarin-supported posters will be presented at the American Diabetes Association 79^th Scientific Sessions in San Francisco, June 7 – 11, 2019.  All three posters highlight important findings regarding the challenges of current treatment options for diabetes patients with cardiovascular risks.  More than 30 million adults in the United States have diabetes, 10 million of whom are considered at elevated risk for cardiovascular events, despite being on cholesterol-management medicines.^1,2

“We have learned through research that cholesterol and diabetes management is not enough to effectively treat cardiovascular disease in patients with diabetes and other risk factors,” said Craig Granowitz, M.D., Ph.D., chief medical officer of Amarin.  “Cardiovascular disease is the No. 1 cause of death in people with diabetes. We applaud the ADA for highlighting the need to better understand and address increased cardiovascular risk in patients with diabetes.”

https://www.globenewswire.com/news-release/2019/06/07/1865933/0/en/CORRECTING-and-REPLACING-Amarin-to-Present-Findings-Regarding-Challenges-of-Current-Treatment-Options-in-Reducing-Cardiovascular-Risks-for-Diabetes-Patients-Even-for-Those-With-Con.html

American Diabetes Association 79th Scientific Sessions

The American Diabetes Association (ADA) will host its 79th Annual Scientific Sessions in San Francisco, California, from Friday, June 7, through Tuesday, June 11, 2019.¹

Attendees can look forward to over 2000 original research presentations and 180 sessions at ADA 2019. Amongst the new trial data being presented, some of the most highly anticipated findings are from cardiovascular disease risk prevention trials, including the REWIND trial (Researching CV Events with a Weekly Incretin in Diabetes), being presented Sunday, June 9 at 4:30 _PM, and the CAROLINA trial(Cardiovascular Safety of Linagliptin), being presented Monday, June 10 at 4:30 _PM.¹

Other notable presentations to look for at 79th Scientific Sessions:¹

The D2d study, launched in 2013, is the largest ever clinical trial designed to explore the effects of vitamin D supplementation on delay of diabetes onset. Results will be unveiled at ADA 2019 for the first time.

(Friday, June 7, 11:30 _AM -12:30 _PM)

The TODAY2 Study, documenting the course of type 2 diabetes and its comorbidities (renal, cardiac, eye, nerve) in the transition from youth to young adulthood.

(Saturday, June 8, 1:45-3:45 _PM)

The PREVIEW study, a global trial that used meal replacements, diets of varying compositions, and 2 physical activity strategies to gain insights into weight loss maintenance and diabetes prevention.

(Saturday, June 8, 4:00-6:00 _PM)

TrialNet results, which will cover findings from the Teplizumab Prevention Trial of individuals with type 1 diabetes with multiple antibodies and abnormal glucose tolerance. In addition, data from 2 other TrialNet studies will be presented.

(Sunday, June 9, 8:00-10:00 _AM)

The RISE Clinical Trials, investigating the loss of beta-cell function in type 2 diabetes. Presenters will discuss the pathogenesis of the disease by comparing results from the Adult Medication Study with data from youth with the same glucose tolerance abnormalities.

(Sunday, June 9, 12:00-1:30 _PM)

The DECLARE-TIMI 58 trial, which assessed patients with diabetes and risk factors for atherosclerotic cardiovascular disease receiving dapagliflozin. The session at ADA 2019 will cover renal end points and other safety aspects.

(Sunday, June 9, 2:15-4:15 _PM)

The CREDENCE and CARMELINA trials, for which key findings will be reviewed and new data analyses presented. These major trials explored the effects of canagliflozin and linagliptin, respectively, in patients with type 2 diabetes at high risk for renal and cardiovascular complications.

(Tuesday, June 11, 7:30-9:30 _AM)

The PIONEER trial program, comparing the efficacy and safety of orally administered peptide drugs with other antihyperglycemic agents.

(Tuesday, June 11, 9:45-11:45 _AM)

Of note, the ADA is now offering a mobile application available from Google Play or the App Store to help create personalized itineraries and stay connected throughout the conference.¹ Attendees are encouraged to wear red on Sunday, June 9th, to support the ADA’s mission to prevent and cure diabetes.²

Visit Endocrinology Advisor’s conference section for continuous coverage from ADA 2019.

American Diabetes Association 79th Scientific Sessions: What to Expect

Sanofi bets on new CEO to drive sluggish drug sales

In veteran drug salesman Paul Hudson, Sanofi’s 100,000-plus employees are getting a new chief executive who relishes a good commercial fight.

The French firm said on Friday it had poached 51-year-old Hudson from Novartis, betting on him to rejuvenate a business hit by sluggish cholesterol drug sales and a diabetes unit facing growing competition for its top seller.

Hudson, the latest of several Novartis executives to exit the Swiss firm, has nearly 30 years of industry experience, including a stint as AstraZeneca’s top U.S. manager.

The Englishman, a skilled public speaker and fan of his hometown soccer team Manchester United, will replace Olivier Brandicourt, 63, who is retiring in September.

At Novartis, Hudson kick-started sales of heart failure medicine Entresto that the firm expected to generate $5 billion but whose sales began at a glacial pace after its 2015 launch.

After heavy marketing investment and a sales push, Hudson turned the drug into a Novartis blockbuster.

“We’re now starting to see the fruits of all the effort we put in,” Hudson told analysts on a Novartis call in April. “Will it continue? We believe it does continue.”

At Sanofi, one of Hudson’s challenges will be to turn around the fortunes of Praluent, a cholesterol medicine that has failed to meet original expectations due to concerns about its price and a bitter patent dispute with rival Amgen.

“The departure of Paul Hudson is regrettable for Novartis, due to his industry experience in the United States,” said Michael Nawrath from Zuercher Kantonalbank.

But his knowledge of the world’s biggest drugs market will be Sanofi’s gain.

Hudson, awarded an honorary doctorate at his alma mater Manchester Metropolitan University, also has to defend Sanofi’s patent-expired insulin Lantus, a top earner at 3.6 billion euros ($4 billion) even after a 20 percent drop in sales.

Competition will come from Mylan’s generics and even Novartis, which in 2018 signed a deal with China’s Gan & Lee to make Lantus copies.

Hudson has proved a tenacious salesman at Novartis, winning approval for the world’s costliest medicine, gene therapy Zolgensma for spinal muscular atrophy, at $2.1 million per patient.

Novartis said Hudson’s replacement would be Marie-France Tschudin, 48, who has led the Swiss firm’s European cancer unit after joining the company in 2017. She previously worked at Celgene’s cancer business.

It marks another change at the top of Novartis, where most of its executive committee was appointed in the last two years.

“The turn-over at the Novartis executive committee continues at high speed,” Bank Vontobel analyst Stefan Schneider said.

This week, Samit Hirawat, head of oncology drug development, left for Bristol-Myers Squibb, while Novartis’s cancer chief, Susanne Schaffert, has only been in her post since January. In March, the Swiss firm hired a new generics head, Richard Saynor, from GlaxoSmithKline.

A Novartis spokesman said Novartis had a deep bench of global experts to fill talent gaps left by Hudson and others.

https://www.marketscreener.com/ASTRAZENECA-4000930/news/France-s-Sanofi-bets-on-new-CEO-to-drive-sluggish-drug-sales-28723174/

Staph Bacteria Tied To Food Allergies in Kids

Target Audience and Goal Statement: Allergists, pediatricians, dermatologists, nutritionists, emergency department physicians, family medicine physicians

The goal was to explore the association of Staphylococcus aureus colonization with specific immunoglobulin E (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity.

Questions Addressed:

• What was the association between S. aureus and food allergy?
• Was any association of S. aureus colonization with sIgE production to common food allergens and food allergy in early childhood independent of eczema severity?

Synopsis and Perspective:

Nearly one in twenty five school-age children have food allergies. Some common foods — including peanuts, eggs, milk, tree nuts, fish, shellfish, soy, and wheat — trigger over 90% of the allergic reactions in affected individuals.

Parent-reported childhood food allergies are on the rise, according to a U.S. household surveyconducted from 2015 through 2016. About 42% reported at least one or more lifetime food-allergy related emergency department visits. IgE-mediated food allergy is a prime reason for anaphylaxis warranting such a visit. Many survey respondents (40.7%) had a current epinephrine auto-injector prescription.

Lead researcher, Olympia Tsilochristou, MD, of Kings College London, and colleagues recently reported in the Journal of Allergy and Clinical Immunology that S. aureus bacteria on the skin of young children with severe eczema may be one of the factors contributing to the chance of developing food allergies.

S. aureus is found in the nose and on the skin of healthy individuals. However, it tends to be more common in eczema sufferers.

Most of the study participants with skin S. aureus had concurrent moderate and severe eczema at all time points. Evaluations at the 12- to 30- and 60- to 72-month intervals showed that eczema significantly worsened in participants with immediately preceding skin S. aureuscolonization compared to uninfected counterparts. Study participants with skin S. aureuspositivity at any time during the study period also produced sIgE to hen’s egg white, peanut, and cow’s milk. This indicated that the participants were allergic to those foods.

“Participants with S. aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity,” the researchers wrote.

Results were derived from a secondary analysis of the Learning Early About Peanut Allergy (LEAP) study and a 12-month extension of the LEAP study, known as the Persistence of Oral Tolerance to Peanut (LEAP-On) trial. The LEAP study enrolled infants ages 4-11 months with severe eczema, egg allergy, or both. The babies were randomized to therapeutic peanut consumption or peanut avoidance, and all had eczema clinical evaluation and culture of skin and nasal swabs at baseline.

The follow-up LEAP-On study assessed the children at age 72 months, after 12 months of peanut avoidance in both groups.

Skin and nasal swabs were obtained at baseline and at ages 12, 30, and 60 months. A total of 48.8% of the participants had some form of S. aureus colonization (32.2% skin and 32.3% nasal) on at least one LEAP study visit, with most having just one positive test result. The greatest rates of colonization were recorded at 4-11 months of age.

Early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. Reduction in the prevalence of peanut allergy following eating peanuts until the age of five years, persisted at the age of six years (after 12 months of not eating peanuts).

However, this related study showed that, even if they ate peanuts at a young age, infants whose skin and noses were colonized with S. aureus were more likely to develop a food allergy.

“These findings indicate that S. aureus may have reduced the chance of young infants gaining tolerance to peanut, even if peanut was eaten in early childhood,” said co-author, Dr. George Du Toit, a King’s College professor.

While the team used bacteriological culture techniques and not DNA-based testing, they pointed out that they were able to enumerate live microorganisms and did not have to rely on possibly identifying remnant non-viable genetic material from a prior infection. They acknowledged that they did not genotype the isolated strains and that it was not possible to match organisms over time and between skin and nasal swabs. Other study limitations cited by the team were only collecting swabs on four occasions in the LEAP study and none in the LEAP-ON study. Diagnostic food challenges were only undertaken for peanuts and they also cautioned that associations were based on “small numbers of LEAP study consumers with peanut allergy as it is reflected in the wide CIs [confidence intervals] around the ORs [odds ratios].” Tsilochristou’s group could also not rule out the possibility of confounders.

Source Reference: Journal of Allergy and Clinical Immunology 2019; DOI: 10.1016/j.jaci.2019.04.025

Study Highlights: Explanation of Findings

This secondary analysis of the LEAP and LEAP-on studies was conducted to better understand the relationship between S.aureus and food sensitization/allergy by correcting the analyses for eczema severity. About half of the LEAP participants were colonized with S. aureus. Eczema severity, persistence, and deterioration could be correlated to skin colonization with S. aureus. Interestingly, hen’s egg white and peanut sIgE levels at each visit in the LEAP and LEAP-On studies were significantly linked with skin S. aureus positivity at any LEAP study time point, even after correcting for eczema severity. High-level hen’s egg white and peanut sIgE production reflected a stronger relationship. Similarly, a high-level sIgE response to milk at 30, 60, and 72 months of age was related to any skin S. aureus colonization. Tsilochristou’s group interpreted the collective results as meaning that S. aureus was associated with allergies to a hen’s egg, peanuts, and cow’s milk.

It is worth noting that 42.7% and 38.1% of baseline participants with an egg allergy had persistent egg allergy at 60 and 72 months of age, respectively. This finding contrasted with previous literature evidence suggesting that allergy to a hen’s egg typically resolves during early childhood. Researchers concluded that S. aureus can prevent the acquisition of natural tolerance to a hen’s egg.

“Our study reveals that aside from eczema severity, this bacterium that patients with eczema commonly become colonized with could be an added risk factor for food sensitization and allergy,” Tsilochristou said in a related report.

“S aureus has been associated with more severe forms of atopic diseases, and our data extend these observations in patients with food allergy,” Tsilochristou’s group concluded.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

Primary Source

Journal of Allergy and Clinical Immunology

Source Reference: Tsilochristou O, et al “Association of Staphylococcus aureus colonization with food allergy occurs independently of eczema severity” J Allergy Clin Immun 2019; DOI: 10.1016/j.jaci.2019.04.025.

Secondary Source

MedPage Today

Source Reference: Boyles S “Common Skin Bacterium Linked to Food Allergy Risk in Kids” 2019.

https://www.medpagetoday.org/allergyimmunology/allergy/80323?_ga=2.41751074.1830602290.1559775994-1125047970.1528569052