Update: Oralair approved for grass pollen allergy

The FDA has approved the first product for oral immunotherapy! 

Oralair is a tablet containing five grass allergens; Sweet Vernal, Orchard, Perennial Rye, Timothy and Kentucky Blue Grass. It is manufactured by Stallergenes, a French pharmaceutical company. It will be marketed and sold in the United States by Greer Laboratories.

Allergy immunotherapy is the most effective treatment for environmental (and possibly food) allergies. It is all natural, containing only the allergens you are allergic to, and the only treatment that prevents disease. Immunotherapy can be given as a shot, drop or tablet.

It is no surprise that our first [glossary slug=’sublingual’]sublingual[/glossary] option is coming out of Europe. For many years, allergists in Europe have chosen the sublingual route rahter than subcutaneous (shots). There are other differences in the way allergies are treated here and abroad. Most sublingual products contain only one allergen. For example, grass pollen. However, up to 40% of patients have allergy to more than one substance. Allergists in the United States attempt to treat as many of the patient’s allergies as they can, administering a mix of several allergens in shot form. For example, grass pollen plus dust mites. Here is a more complete discussion, see this article (Allergy Tablet Approval Warrants Caution for Some).

It is not clear which method is better, one allergen or many. Probably there is no one right answer that would apply to everyone. The same is true in the debate, shots vs. drops/tablets. Shots are more effective but drops/tablets are more convenient. In the end, the approval of ORALAIR provides an additional treatment option for allergy specialists and their patients. If more patients get treatment then we all benefit.

UPDATE (2): TOO LATE FOR 2013

For best results, Oralair should be started 2 months prior to the grass pollen season. In the northeast, May and June are the months with peak grass pollen levels. If Oralair is available this May then it would be too late for 2013.

PRESS RELEASE (excerpts):

– Grass allergy is the most common seasonal allergy in the United States and most people are allergic to more than one type of grass. ORALAIR contains a mix of five grass pollens: Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass. The five grass pollens contained in ORALAIR represent those to which most patients in the U.S. are exposed.

– ORALAIR is indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for any of the five grass species contained in this product. ORALAIR is approved for use in persons 10 through 65 years of age.

– ORALAIR is a tablet that dissolves under the tongue. The first dose is taken in the doctor’s office under medical supervision, and subsequent doses are administered once a day by the patient or the patient’s caregiver. ORALAIR treatment should be started four months before the expected onset of each grass pollen season and continued throughout the season. Allergy symptoms are reduced beginning with the first grass pollen season.

– ORALAIR was originally approved in Europe in 2008 and is currently authorized in 31 countries around the world, including most European countries, Canada, Australia, and Russia for the treatment of grass pollen allergy. In Canada, ORALAIR was launched in 2012, making it the first allergy immunotherapy tablet to be registered and marketed in North America. Worldwide post-marketing experience with ORALAIR includes more than 20 million doses given to more than 110,000 patients.

– ORALAIR has been approved based on results from an extensive clinical development program. ORALAIR has been studied in double-blind, placebo-controlled trials, in both Europe and the United States in over 2,500 adults and children. The results of these trials demonstrated that pre-seasonal and co-seasonal treatment reduces patients’ allergy symptoms and their need for symptom-relieving medication. In the clinical development program, the most common adverse reactions for ORALAIR (reported in >=5% of patients) were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain.

Stress & Allergy

It is clear to those suffering, allergies cause stress. Constant runny nose, decreased quality of sleep, missed days at school and work are among the many reasons why. A new study from Ohio State University* flips this conclusion on its head and asks; can stress cause allergies?

Our bodies immune system is not limited to the nose. It involves organs and cells throughout the body. The inflammatory chemicals produced during an allergic reaction can have wide ranging effects. Likewise, the endocrine system will respond to stress by increasing (or decreasing) hormone levels throughout the body. These two systems do not live in isolation.

In this study, subjects were asked to complete daily diaries. They recorded allergy symptoms, mood and stress levels using a secure website. The data showed that patients with higher stress scores experienced more allergy flares. Also, there was a similar relationship between negative mood and rhinitis symptoms. For most patients, the effect was spread out over time, a stressful day did not occur together with a bad allergy day. However, for a few more sensitive subjects there was a pattern of increased allergy symptoms on stressful days.

The authors conclude that allergic individuals with persistent emotional stress have more frequent allergy symptoms. They recommend stress reduction techneques, such as meditation for the treatment of allergy symptoms. However, it should be noted, this study does not prove cause and effect. There is no evidence that the stress causes the allergy as opposed to the allergy causing the stress. Either way, stress-reduction is a good thing.

 

* Patterson A, Yildiz V, Klatt M, Malarkey W. Perceived stress predicts allergy flares. Ann Allergy Asthma Immunol 112 (2014) 317-321.

What is Eosinophilic Esophagitis?

Eosinophilic esophagitis (EoE) is an inflammatory condition affecting the esophagus (the tube that connects the throat with the stomach). The esophagus contains too high a number of eosinophils, an allergic white blood cell. This causes several gastrointestinal symptoms, including difficulty swallowing, nausea,vomiting and reflux.

Diagnosis: To confirm the diagnosis requires an upper endoscopy and biopsy. Unfortunately, no less invasive procedures are available to diagnose or monitor EoE.

The Role of Allergies: The majority of individuals with EoE have family histories of allergies and symptoms of one or more allergic disorders such as asthma, nasal allergies, atopic dermatitis or food allergy. Food allergy is a major cause of EoE in children, and a less probable factor in adult EoE. Environmental allergies such as dust mites, animals, pollens and molds may also play a role.

Treatment of EE:
– Diet. Avoidance of common allergens (milk, egg, soy, wheat, nuts and fish) may eliminate the symptoms and underlying inflammation of EoE. Atopy patch testing may help to guide food choices.

– Medications. Steroids are effective at shutting down inflammation and eosinophil production. Local delivery helps to lessen side effects. This is achieved by swallowing those steroids indicated for asthma (either a fluticasone inhaler or budesonide for the nebulizer machine).

The initial diagnosis of EoE can be overwhelming. Working closely with your healthcare team is the best way to assure you are receiving proper care. Additionally, families often benefit from participation in support groups, such as the American Partnership for Eosinophilic Disorders (APFED) at www.apfed.org.

Xolair approved for chronic hives

The FDA has approved omalizumab (Xolair) for the treatment of chronic hives. This is the first medication with a specific indication for [glossary slug=’chronic-idiopathic-urticaria’ /] (CIU). There are many patients with CIU that remain symptomatic, covered in hives and itchy despite multiple medications. The addition of Xolair may help these patients get their symptoms under control.

The good:

– Current treatment options are limited and often ineffective.

– Convenience. Xolair is given as an injection on a monthly basis. Current medication regimens may include up to 20 pills per day.

The bad:

– Xolair is expensive and will require pre-approval.

– Several clinical studies have demonstrated a high degree of safety. However, there are concerns that Xolair use may increase the risk of cardiac events and severe allergic reactions.

The ugly:

– Xolair, like other available medications, suppresses the hives but does not fix the underlying problem. Optimally, a cause can be identified and corrected or avoided.

 

Allergy shots, a new source of savings

dollar_icon

dollar_iconAllergies are common and costly. Total costs are in the billions. An increasing proportion of this number is being shifted to the patient, in the form of higher copays and deductibles. The price of health care is now a real part of our health care conversation.

When choosing the most appropriate allergy treatment, doctors and patients should consider efficacy, side effects and cost. The most common treatment options for allergy patients are:

1. Avoidance

2. Medications

3. Immunotherapy (also know as allergy shots)

It is well established that allergy shots provide the most relief but are they worth the cost? A recent study* used an advanced computer model to address this question.  They considered these factors most important in making a decision:

  • patient age
  • life expectancy
  • number of months per year medications are required
  • cost of medications
  • number of allergies
  • duration of immunotherapy (3 vs 5 years)

A virtual allergy patient was put through economic analysis. He was doing well using an intra-nasal steroid, the gold standard in treatment. Unfortunately, nasal sprays do not alter the course of the disease, symptoms recur shortly after they are discontinued. There is no endpoint for the patient.  On the other hand, immunotherapy can induce long term tolerance after only 3-5 years of therapy. This means that the benefits will continue long after your shots are finished. Despite this advantage, allergy shots are usually reserved for patients who fail medical therapy. Economically, younger patients would be better off with 3-5 years of shots, not a lifetime of nasal steroids.

cost_chart

 

 

 

 

 

 

 

 

The attached figure demonstrates a large area where immunotherapy is more cost effective than medical therapy. It must be noted, this figure only represents those patients that are doing well on nasal sprays.  For patients who continue to have symptoms despite medications, the decision would be shifted heavily in favor of allergy shots.

 

* Kennedy J, Robinson D, Christophel J, Borish L, Payne S. Decision-making analysis for allergen immunotherapy versus nasal steroids in the treatment of nasal steroid‐responsive allergic rhinitis. American Journal of Rhinology & Allergy.  2014; 28(1) 59-64.

Difficult to treat eczema: a review of medications

Sometimes moisturizers and steroid creams aren’t enough. Many patients with severe eczema (atopic dermatitis, AD) require oral medications to keep their skin clear and itching under control. A recent article out of Amsterdam and Germany, reviewed the risks and benefits of several systemic therapies*. Here are the recommendations:

  • Cyclosporin A: first-line short term treatment option for moderate to severe AD. Higher doses (5 mg/kg/day) lead to a more rapid response and higher efficacy.
  • Azathioprine: second-line treatment option.
  • Methotrexate: third-line treatment option for adults.
  • IFN-γ: third-line treatment option.
  • Systemic steroids: not recommended.
  • Intravenous immunoglobulin: not recommended.
  • Montelukast (Singulair): not recommended.
  • Traditional Chinese herbal medicine (TCHM): not recommended.
  • [glossary slug=’mycobacterium-vaccae’ /]: not recommended.
  • Thympopentin-5 (an immunostimulant): not recommended.

What was not included:

What needs to be stated:

  • All of these medications can have significant side effects.
  • It is important to maximize topical treatments, including moisturizers and medications.
  • It is important to identify and minimize exposure to triggers, including foods and contact allergens.

 

* Roekevisch E, Spuls PI, Kuester D, Limpens J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review. Journal of Allergy and Clinical Immunology 2014; 133(2) 429-438.

Probiotics for the prevention and treatment of allergies

 Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit (FAO/WHO 2002). The potential benefits include inhibition of pathogens, improved integrity of the gastrointestinal (GI) barrier and enhanced immune responses. These effects may be useful for the prevention and treatment of multiple allergic conditions.

Rationale:

– Allergies occur more in developed nations. The hygiene hypothesis states that a highly sanitized environment provides insufficient bacterial stimulation at a young age. Without proper ‘training’ the immune system is unable to distinguish harmful bacteria from healthy foods (tolerance).

– As we get older, the GI associated immune system continues to play an important role. Unfortunately, the composition of gut microbiota can be altered by diet, stress, aging, antibiotics or infection.

– The composition and diversity of intestinal microbiota varies in allergic versus non-allergic children.

– Children born via vaginal delivery are less likely to have allergies than those children born via c-section. Exposure to beneficial bacteria in the maternal vaginal tract helps to colonize the child. Also, this benefit may occur in those children who are  breast fed.

Evidence:

– The effectiveness of probiotics for the prevention and treatment of allergies is controversial. There are a large number of published studies with a wide range of results. Several studies show a great benefit and several studies show no benefit at all.

– The variable results are likely the result of variable protocols. The strain of bacteria, the amount of bacteria and the age of the patient are important factors in determining outcome. It is likely that different strains produce different immunologic effects leading to different outcomes. One probiotic may help asthma and another may help eczema. Examples of beneficial probiotics include, Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536.

– Eczema (atopic dermatitis). Probiotics have shown value for preventing eczema when given to expecting mothers. Probiotics have shown value for treating eczema when given to young children.

– Allergic rhinitis (sneezing). Several studies from Japan have shown decreased allergy symptoms for patients with tree pollen allergy.

– Food allergy. Infant formulas supplemented with probiotics may improve the symptoms of milk allergic colitis. Unfortunately, supplementation did not accelerate cow’s milk tolerance in those infants with milk allergy.

Conclusion:

Probiotics may be a useful adjunct in the fight against allergic disease. They provide a natural way to stimulate the immune system. Most importantly, proper timing may prevent future allergies. Further research is needed to determine which strains are useful and when they should be taken.

FDA committee supports approval of two new sublingual allergy tablets

tabletsLast week, the FDA Allergenic Products Advisory Committee unanimously supported approval for two new sublingual allergy tablets (Oralair and Grastek).  Allergy tablets are an alternative to conventional allergy shots. Both tablets are indicated for the treatment of grass pollen allergy. Oralair is made by a French pharmaceutical company Stallergenes and contains 5 different grasses: Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass. Grastek (aka Grazax in Europe) is made by ALK-Abello and Merck and contains only Timothy Grass.  Although both tablets are available in Europe, FDA approval may not occur for a year or more.

For more than a century, physicians have been using the process of desensitization to treat environmental allergies. Introducing small amounts of allergen (i.e. dust mites, pollens) over and over again, helps to re-educate the immune system. Using current dosing regimens, the results are impressive. Large analyses show a decrease in allergy and asthma symptoms of ~ 75%. Other benefits include a decreased need for medications (60%) and decreased risk of developing new allergies or asthma. Unfortunately, these results require commitment and frequent office visits.

Which is better, allergy tablets or shots? 

1. Effectiveness. There have been few good studies comparing allergy tablets (or drops) with shots. Looking at placebo controlled trials (comparing treatment with a ‘fake’ injection or tablet), allergy shots appear to provide higher levels of relief.

Winner: shots.

2. Convenience. Each and every allergy shot must be given in the allergist’s office.  Although the first dose is given at the allergist’s office, allergy tablets are continued at home.

Winner: tablets.

3. Flexibility.  Those tablets currently available (in Europe) contain only single allergens, such as for grass. Other tablets in development include ragweed or dust mites. Allergy shots are customized by allergists to contain multiple allergens, such as for trees, grasses, weeds, dust mites, animal danders and/or molds.

Winner: shots.

4. Compliance. Without completing a recommended course of allergy tablets or shots, patients will not get their optimal result. Unfortunately, neither treatment route has demonstrated a high completion rate. A recent study from the Netherlands  found that only 7% of those getting allergy tablets (or drops) completed the recommended three years of treatment. Surprisingly, that was even worse than the 23% of patients getting allergy shots. One possible reason, allergy shots may be spread out to once monthly versus daily use of allergy tablets.

Winner: neither.

5. Cost. Producing a high quality allergy tablet (or drop) requires significantly higher amounts of material than allergy shots. However, there are less associated costs, i.e. office visits and injections. Unfortunately, an accurate comparison is not possible at this time, until allergy tablets are approved by the FDA, there is no insurance coverage.

Winner: unknown.

6. Safety. Both tablets and shots are well tolerated. Both have the potential to cause local reactions, either an itchy mouth or an itchy harm. Both have the potential to cause systemic (more severe) reactions. Although the risk is low, it is definitely higher with shots (compared to tablets).

Winners: tablets.

6. Conclusion. The best allergy treatment is one that works quickly and lasts forever. Allergy tablets, drops and shots will continue to get better. For example, four doses of an investigational cat vaccine, given over 12 weeks, had a significant improvement in symptoms two years later. Stay tuned.

 

Food additives, an unlikely cause of chronic hives

spicesIf you suffer from chronic hives (urticaria) then you are desperate to find a cause. The one allergy that will fix your problem. Often foods, food additives or food preservatives are suspected. When you break out every day and eat multiple times in a day then there is bound to be some overlap. A few months ago, I looked at the evidence for diet changes as a treatment of chronic urticaria (link). There were only a small number of studies with little evidence for or against the role of food allergy in causing hives. A new study attempts to provide a more definitive answer.

The study, from Scripps Clinic in San Diego, California was designed to overcome two main obstacles. The first obstacle is bias. If a patient believes that a food is causing their hives this may result in higher stress, anxiety and more hives. A blinded study is needed to prevent bias. In the final arm of their study, neither patients nor investigators were aware if they were ingesting a food additive or a placebo (sugar pill). The second obstacle is the medication used for treatment. Symptoms are controlled with anti-histamines, if these medications are stopped for the study then the hives will naturally recur. This could result in a false positive. On the other hand, if the patient is on ‘too much’ anti-histamine then a reaction may be masked (a false negative). The author’s solution was to maintain patients on a minimum effective dose of medication.

After completion (ten years), one hundred patients had been challenged with 11 food additives, including:

  • FD&C Yellow 5
  • FD&C Yellow 6
  • Potassium metabisulfite
  • MSG 2500
  • Aspartame
  • Sodium benzoate
  • Methyl paraben
  • Butylated hydroxyanisole
  • Butylated hydroxytoluene
  • Sodium nitrate
  • Sodium nitrite

Although 43 patients reported a history of reaction to food or drug additive prior to the study, NO patients reacted to a double-blind challenge. The conclusion, sensitivity to food additives appears to be rare in patients with CIU, and avoidance is NOT recommended. One study is not proof, but this new information does makes food additives as a singular cause of chronic hives fairly unlikely. We must continue the search for the environmental, infectious and immunologic factors resulting in this burdensome disease.

References:

Rajan JP, Simon RA, Bosso JV. Prevalence of sensitivity to food and drug additives in patients with chronic idiopathic urticaria. J Allergy Clin Immunol Pract. http://dx.doi.org/10.1016/j.jaip.2013.10.002.

Warning: May Contain Peanuts

labelCurrent treatment options for food allergy are limited. Chinese herbal therapy may prevent reactions. Oral desensitization may one day provide a more permanent cure. Unfortunately, neither treatment is available today. Instead, patients and parents are instructed to avoid a food (or group of foods) without error.

When eating out, you must rely on the kitchen staff. When eating at home, you must rely on the ingredient list provided by the manufacturer. These food labels may be inaccurate or difficult to interpret.

Reading a label is an acquired skill. In order to be successful, parents need to know the benefits and limitations of current labeling laws. Most important is the Food Allergen Labeling and Consumer Protection ACT (FALCPA); passed in 2004 and in effect since 2006. This law requires labels to plainly state, in clear english, if they contain a major food allergen. The major food allergens are milk, egg, fish, crustacean shellfish, peanut, tree nuts, wheat and soy). These ingredients must be listed if they are present in any amount, even in colors, flavors or spice blends. Additionally, the manufacturer must list the specific nut and/or seafood that is used. The food name can be found in one of two places;

1. Within the ingredient list; i.e. “natural flavoring (egg)”.

2. An adjacent “contains” statement; i.e. “Contains egg.” These are usually in bold type.

Passing this law was a step in the right direction. Unfortunately, there remain limitations;

• Only 8 foods groups are required. If you are allergic something else (i.e. sesame seed), it may not be included in the “contains” statement. If you are sensitive to something else (i.e. gluten or preservatives), it will not be included. You must read the full ingredient list.

• Alcoholic beverages, meat, poultry, and certain egg products are not regulated.

• Advisory labels for possible cross contamination are voluntary and inconsistent. Examples include, “May contain traces of peanut,” “Processed on equipment that also processes peanuts,” or “Made in a facility that processes peanuts.”

FALCPA requirements do not apply to potential or unintentional presence of major food allergens in foods resulting from ‘cross-contact’ situations during manufacturing, e.g. because of shared equipment or processing lines. It is left to the discretion of the company if they would like to include a warning statement. The wording of such statements is also left to the company. There are no parameters. This lack of consistency lowers the value of all statements. Their high prevalence and ambiguity leads consumers to doubt their legitimacy. In the end, warning statements are often ignored.

The warning statement is only valuable if can convey the risk of contamination and help parents to make informed decisions. Useful information would include, the probability that the product contains peanut and the amount of peanut that may be present. Several studies have analyzed foods in order to answer these questions. A study from Ireland, looking at 38 food products with a nut statement, found detectable peanut in 5% of foods. The amount of nut protein varied from 0.14 to 0.52 mg per serving (or less than 1/100 of a peanut).  A more recent US study found that 8.6% of foods with a peanut advisory contained a detectable level of peanut protein. Nutrition bars contained the highest levels. Other high risk foods include chocolate candies, cookies and baking mixes.

The problem is not limited to peanuts and tree nuts. In a 2010 study of milk, egg, and peanut; the highest level of contamination was for milk (10.2%). Overall 5.3% of foods with an advisory label were contaminated. The levels of milk found were within the range that may cause a reaction. On the other hand, peanut levels were low. It was estimated that the level of peanut contamination would cause a reaction in only 5% of peanut allergic children, making the overall risk of reaction less than 1%.

The amount of protein that may cause a reaction (threshold) varies dramatically in different children. This makes label standards difficult. The Australian Allergen Bureau have been using investigation and statistics to overcome this obstacle. A Voluntary Incidental Trace Allergen Labeling (VITAL) program was developed to make a single simple standardized precautionary statement available to assist food producers in presenting allergen advice consistently for allergic consumers. VITAL not only assists food producers in assessing the potential impact of allergen cross contact in each of their products but also specifies a particular precautionary allergen statement to be used according to the level of cross contact identified. The initial goal was to label foods with peanut levels higher than 1.5 mg, the amount likely to cause a reaction in 5% of peanut allergic children. With VITAL 2.0, the level drops to 0.2 mg, only 1% of peanut allergic children will react at this level. Additionally, VITAL 2.0 provides manufactures with an action grid containing 24 total foods.

Recommendations that are not specific are not helpful. At this point, the safest course is to avoid any food that declares the major allergen. Parents must read labels ALL of the time. Ingredients can change. In the end, if you are unsure whether or not a product could be contaminated, you should call the manufacturer to ask about their ingredients and manufacturing practices.