Experimental Therapy for Children With Peanut Allergies Shows Promise

Oral immunotherapy shows promise as experimental new therapy for children with peanut allergies. Image: iStock.com/DonNichols

Oral immunotherapy shows promise as experimental new therapy for children with peanut allergies. Image: iStock.com/DonNichols

There may be new hope for children with severe peanut allergy, a condition that not only is potentially fatal, but also can cause much anxiety for both children and parents alike.

This week, 2 new studies discuss research findings on the use of oral immunotherapy in children with peanut allergies, which affects up to 1.4% of children in high-income countries. Oral immunotherapy involves having individuals with an allergy to a substance ingest a tiny amount of that substance under close clinical monitoring, and gradually increasing this exposure over an extended period of time. The goal is to eventually reach a point where the body can tolerate a reasonable amount of the substance without a severe allergic reaction, at which point the individual is deemed “desensitized.”

The first study, released yesterday in The Lancet, is the first phase 2 randomized clinical trial showing that this type of immunotherapy may work for children with peanut allergies. Researchers at Cambridge University in England randomly assigned 99 children aged 7 to 16 years to receive either 6 months of oral immunotherapy or no treatment (aside from continuing to avoid exposure to peanuts). The oral immunotherapy involved feeding children daily peanut protein, starting with 2 mg and slowly increasing to 800 mg (roughly 5 peanuts) per day.

Of the 39 children who completed the oral immunotherapy regimen, 24 of them (62%) were successfully desensitized compared with none in the control group. Successful desensitization was defined as having no allergic reaction after ingesting 1400 mg of peanut protein (approximately 10 peanuts), as measured by a standard clinical test for food allergy called the double-blind, placebo-controlled food challenge.

As expected, children in the immunotherapy group had more adverse reactions than the control group, but most were mild and involved itching, mild wheezing, and rash. There were no serious adverse events.

Although these preliminary results are promising, much information is still lacking about how oral immunotherapy works on a molecular level. This is an area of active research, and a phase 1 study released today in the Journal of Allergy and Clinical Immunology may shed some light on this process.

The study, conducted by researchers at Stanford University, included 43 patients who were randomly assigned to either oral immunotherapy (a 24-month regimen culminating in exposure to 4000 mg of peanut protein) or no therapy. Of the 23 patients given oral immunotherapy, 20 became desensitized (or tolerant) to peanuts. The researchers then looked to see if tolerance to peanuts was maintained after the desensitized individuals stopped immunotherapy for 3 months and completely avoided peanut exposure. They found that among the 20 individuals who originally became desensitized, only 7 remained so after 3 months.

The Stanford team also looked at several immune system markers in the study participants. They found that the 7 participants who remained tolerant to peanuts had increased activity of a special type of T lymphocyte called the antigen-induced regulatory T-cell. Furthermore, specific genes in those T-cells had lower levels of DNA methylation, a process in which chemical tags are added to specific DNA segments (genes) that affect how those genes are expressed by the cell. These epigenetic changes in T-cell DNA (changes not in the DNA code itself, but in the patterns of chemical tags attached to it) might be one of the underlying mechanisms for peanut desensitization following oral immunotherapy, although more research is needed on the topic.

Ultimately, oral immunotherapy is still very much an experimental therapy that is far from routine clinical use. “Further studies in wider populations are needed,” noted Pamela Ewan, MD, one of the authors on the Lancet study, in a statement. “It is important to note that oral immunotherapy is not a treatment people should try on their own and should only be done by medical professionals in specialist settings,” she cautioned.

More Evidence Exonerates Vaccines From Autism Link

The antigenic load of childhood vaccines doesn’t increase the risk of autism spectrum disorder, according to a new study. (Image: zorani/iStockphoto.com)

The antigenic load of childhood vaccines doesn’t increase the risk of autism spectrum disorder, according to a new study. (Image: zorani/iStockphoto.com)

A new analysis adds to existing evidence showing that recommended childhood immunizations do not increase the risk of autism spectrum disorder (ASD).

Despite a 2004 review from the Institute of Medicine that concluded the measles, mumps, rubella, and thimerosal-containing vaccines don’t increase autism risk, concerns have persisted. Recent surveys indicate that about one-third of parents worry that their children receive too many vaccinations and that the cumulative effect of those vaccines may cause autism. At least 10% of parents refuse or delay vaccinations for their young children, believing it’s safer than following the Centers for Disease Control and Prevention’s (CDC) recommended vaccination schedule.

Because many parents’ concerns have focused on the number of vaccinations children receive, researchers at the CDC and Abt Associates of Bethesda, Md, calculated ASD risk based on the number of antibody-stimulating antigens that children are exposed to when they’re vaccinated. The study authors noted that even though the routine childhood immunization schedule includes more vaccines now than in the late 1990s, the amount of antigens in some vaccines has decreased substantially since then. For example, children who were fully immunized by age 2 years in 2012 were exposed to no more than 315 antigens. But in the late 1990s, fully immunized children were exposed to thousands of antigens. Continue reading

Author Insights: Injection-free Immunotherapy May Be Helpful for Desensitizing Patients to Respiratory Allergens

Sandra Y. Lin, MD, of Johns Hopkins School of Medicine, and her colleagues found that daily administration of tiny doses of allergens under the tongue helped desensitize patients with asthma or allergic rhinitis to those allergens.

Sandra Y. Lin, MD, of Johns Hopkins School of Medicine, and her colleagues found that daily administration of tiny doses of allergens under the tongue helped desensitize patients with asthma or allergic rhinitis to those allergens.

Giving patients with allergic rhinitis or asthma a daily dose of allergens under the tongue appears to be an effective option to help desensitize them to respiratory allergens, according to a review published in JAMA today.

Patients who experience respiratory or asthma symptoms triggered by exposure to allergens have long had the option of undergoing immunotherapy to desensitize them to the offending allergen. In the United States, this typically involves frequent visits to the allergist for injections of tiny doses of allergens over a prolonged period. But in Europe, a less invasive approach, giving tiny doses of allergens in drops or a dissolving tablet administered under the tongue, has become popular. This strategy, called sublingual therapy, accounts for 45% of the immunotherapy offered in Europe, according to the study’s authors. There are no sublingual immunotherapy products approved by the US Food and Drug Administration (FDA) for use in the United States, but some physicians do offer the therapy off label.

To assess the efficacy of sublingual immunotherapy, Sandra Y. Lin, MD, associate professor in the department of otolaryngology, head, and neck surgery at Johns Hopkins School of Medicine, and her colleagues were commissioned by the Agency for Healthcare Research and Quality (AHRQ) to conduct a review of the evidence to date.

Lin and her colleagues found a moderate amount of evidence overall supporting the efficacy of sublingual therapy. They classified the evidence for the use of sublingual therapy for asthma as strong, with 8 of 13 studies finding a 40% or greater improvement in symptoms among treated individuals compared with a control or alternate therapy group; evidence of efficacy for allergic rhinitis was moderate, with 9 of 36 studies showing a 40% or more improvement in symptoms. Overall, medication use among individuals treated with sublingual immunotherapy decreased 40% or more in 16 of 41 studies.

Lin discussed the findings on sublingual therapy with news@JAMA.

news@JAMA: What is sublingual immunotherapy and why might patients choose it over injections?

Dr Lin: You introduce small amounts of what the person is allergic to over the course of years. It just like immunotherapy injections, but for the shots you have go to the physician’s office. Injections typically start out once or twice a week and spread out over time. Subcutaneous immunotherapy is taken daily.

There are certain patients who don’t like shots, especially children. Some people may not have access to specialists to get the shots regularly.

news@JAMA: How often is sublingual immunotherapy offered in the United States?

Dr Lin: It’s kind of unknown. The last survey was about 5 years ago, and at that time it looked like it was not common. There are US physicians (including otolaryngologists, allergists, and family physicians) who use it off label. They use allergens that are FDA-approved for injection use for sublingual immunotherapy.

news@JAMA: What did you learn from your review about the effectiveness of this approach?

Dr Lin: It looks like it is effective, but for physicians in United States, we would want more studies on the allergens used here to determine the most effective doses. The majority of studies we reviewed were done outside of the United States; because of differences in the potency of allergen products from country to country, it may be difficult to translate what an effective dose in the United State would be. Only 7 of the 63 studies we reviewed were from the United States or Canada.

news@JAMA: What were you able to learn about the safety of this approach?

Dr Lin: It wasn’t a comprehensive review of safety; only randomized controlled trials were included in the review. In the studies we reviewed, there were no serious or life-threatening adverse events. But a lot of studies on the safety of therapies are not randomized controlled trials and would not have been included.

news@JAMA: This therapy is already widely used in Europe. Why isn’t it being used as much here?

Dr Lin: It would probably be more widely used if there were FDA-approved sublingual allergens. The dose translations are difficult.

news@JAMA: What should patients know about this therapy?

Dr Lin: Many patients are aware of the therapy and there is a demand. There are patients seeking this out. I think sublingual therapy would be a great way to reach younger patients and those patients in underserved areas of the United States where patients can’t easily get to a physician’s office.

Author Insights: No Apparent Increase in Shingles Risk for Patients With Rheumatoid Arthritis Who Take Certain Immunosuppressants

Kevin L. Winthrop, MD, MPH, of Oregon Health & Science University in Portland, and colleagues found that patients with rheumatoid arthritis who began taking a certain class of powerful immunosuppressant medications did not appear to have an increased risk of developing shingles. (Image: George Petricek, Casey Eye Institute, Oregon Health & Science University)

Kevin L. Winthrop, MD, MPH, of Oregon Health & Science University in Portland, and colleagues found that patients with rheumatoid arthritis who began taking a certain class of powerful immunosuppressant medications did not appear to have an increased risk of developing shingles. (Image: George Petricek, Casey Eye Institute, Oregon Health & Science University)

Concern that a front-line class of immunosuppressant drugs used to treat rheumatoid arthritis might increase a patient’s risk of developing herpes zoster (shingles) appears to be unfounded, according to research appearing today in JAMA.

Shingles, caused by a reactivation of the herpes zoster virus in individuals who previously had chickenpox (caused by the same virus), is characterized by a painful rash and can also cause depression and long-term disability. The condition tends to develop in elderly individuals or those who are immunosuppressed. Patients with rheumatoid arthritis, a disease that involves dysregulation of the immune system, are up to 3 times more likely to develop shingles than people without the disease.

Although anti–tumor necrosis factor (anti-TNF) therapy is considered the treatment of first choice for patients first diagnosed with moderate to severe rheumatoid arthritis, the medications’ powerful immunosuppressant effects prompted concerns about whether their use would increase the risk for shingles in such patients.

But the JAMA researchers found no increased shingles risk for patients with rheumatoid arthritis and other inflammatory diseases (inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis) who started using an anti-TNF drug compared with those who began taking nonbiologic disease-modifying antirheumatic drugs. The findings are based on retrospective analysis of 59 066 new users of these medications between 1998 and 2007. Continue reading

Author Insights: Higher Pertussis Rates in Children Vaccinated With Newer Pertussis Vaccine

The fewer adverse events associated with acellular pertussis vaccines compared with whole-cell pertussis vaccines may come at the cost of slightly less protection from pertussis infection, according an analysis by Stephen B. Lambert, MBBS, PhD, a scientist at Queensland Children’s Medical Research Institute, and his colleagues. Image: Kris Kamusinski, Herston Multimedia Unit, Queensland Health

Acellular pertussis vaccines, which have become favored over whole-cell pertussis vaccines because they are associated with fewer adverse events, may offer children less protection from pertussis, according to a study published in JAMA today.

Ongoing pertussis outbreaks in the United States, Australia, and other parts of the world have prompted speculation about whether changes in pertussis bacteria, inadequate vaccination rates, or other factors might be driving these outbreaks. To probe the role of the shift from whole-cell pertussis vaccines to acellular pertussis vaccines in the 1990s, Australian scientists compared the reported rates of pertussis infection among 58 233 children born in 1998 who were vaccinated with the acellular vaccine, with the whole-cell vaccine, or with some combination of the 2 over the course of the 3-dose vaccination regimen. They found that the average annual rate of pertussis infection between 1999 and 2008 was more than 2.5 times higher among those who received 3 doses of the acellular vaccine than among those who received 3 doses of the whole-cell vaccine (13.2 vs 5.2 infections per 100 000 per year).

Stephen B. Lambert, MBBS, PhD, a scientist at Queensland Children’s Medical Research Institute and one of the coauthors of the study, discussed the implications of these findings with news@JAMA via e-mail. Continue reading

Milk Protein Can Escape Detection in Processed Foods

Enzyme-linked immunosorbent assays may be not be able to detect milk protein residue in some processed foods.  Image: Maria Volchetskaya/iStock.com

Enzyme-linked immunosorbent assays may be not be able to detect milk protein residue in some processed foods. Image: Maria Volchetskaya/iStock.com

Milk-protein residue may slip past the standard test used to detect it in processed foods, according to new research. As a result, millions of young children with milk allergy could unknowingly be exposed to milk proteins that will make them sick.

The finding, presented yesterday at a meeting of the American Chemical Society, showed that the standard enzyme-linked immunosorbent assay (ELISA) used by the food industry can’t always pick out milk proteins that have aggregated or changed shape during thermal and non-thermal food processing. Continue reading

FDA Approves Test to Assess Risk of Deadly Viral Illness Linked to Natalizumab

Individuals who have antibodies to the JC virus are at greater risk of developing a progressive multifocal encephalopathy when taking natalizumab, according to the US Food and Drug Administration. (Image: Arch Neurol. 2002;59[12]:1930-1936)

Patients who test positive for antibodies to the JC virus (JCV) are at elevated risk for developing a deadly viral illness called progressive multifocal leukoencephalopathy (PML) while taking natalizumab (brand name Tysabri), a drug used to treat multiple sclerosis and Crohn disease, warns the US Food and Drug Administration (FDA). The FDA’s alert was issued late Friday, the same day the agency approved a test to identify individuals who have been exposed to JCV.

Clinical trials of natalizumab identified an elevated risk of PML, which causes progressive and often irreversible neurodegeneration, in patients taking the medication. As of January 4, 2012, 201 cases of PML have been identified in 96582 patients treated with natalizumab. Although PML is a rare adverse event, it is particularly concerning because JCV infection is common; it is usually harmless in individuals who are not immunocompromised but can be deadly and difficult to treat in patients who are immunocompromised as a result of a medical condition or treatment with an immunomodulating drug such as natalizumab. A mandatory registry program was created for patients taking the drug in 2006 to help the FDA and the drug’s maker better assess the risk. Continue reading