Immunotherapy Moves Beyond The Basics

Veterinary Allergen Immunotherapists are showing increased interest in different treatment methods, research shows.

With about 150 diplomates of veterinary dermatology, and fewer than 20 of them researching allergen immunotherapy treatments, the profession has relied on the same basic testing and treatment methods for decades until recently, specialists say.

Treatment administration methods are of high interest to veterinary allergen immunotherapists.

Sublingual Immunotherapy

Sublingual immunotherapy, or SLIT, is an alternative to allergy shots. With SLIT, a compound is placed under the animal’s tongue as opposed to being injected, which is seen as a good alternative for pet owners leery of administering routine shots.

“We want to find molecules that increase immunity to the allergens without having to inject the allergen,” says Thierry Olivry, DrVet, Ph.D., Dipl. ECVD and ACVD, a professor at North Carolina State University. “With SLIT, animals and owners could be less anxious about treatment.”

Research on SLIT is being conducted for human use and is not approved by the Food and Drug Administration. But veterinary immunologists predict the treatment will soon be useful in canine cases.

“Testing in dogs for sublingual immunotherapy treatment will begin at NCSU in conjunction with the Japanese RIKEN Center for Allergy and Immunology, a center researching immunotherapy alternatives. Testing is expected to begin by May,” Dr. Olivry says. “The treatment is expected to increase chances of good immune outcomes and increased safety.”

Allergen-specific Therapy

Another area of research at North Carolina is adjuvanted allergen-specific immunotherapy. In this method, immunostimulants are injected along with allergens to increase the immunological changes associated with positive outcome.

A current project also funded by RIKEN is looking at an adjuvant stimulating the activation of very rare immune cells named Natural Killer T cells.

“Preliminary results with the allergen-specific immunotherapy research are very encouraging,” Olivry says.

“We are now performing a dose-escalation phase. It is likely that the positive immune changes seen in immunotherapy may be reproduced without any allergens.

“This could lead to the development of a potent allergen-independent immunotherapy that could be applicable to most patients with IgE-mediated atopic dermatitis,” Olivry says.

Preliminary investigations on such methods are under way at the NCSU Center for Comparative Medicine and Translational Research by Gregg Dean, DVM, Ph.D., Bruce Hammerberg, DVM, Ph.D., and Olivry.

Antihistamines

Morris Animal Foundation is sponsoring Olivry’s research on atopic dermatitis to determine whether oral administration of the antihistamine hydroxyzine, which is absorbed into a dog’s bloodstream, is metabolized sufficiently to suppress allergic reactions.

Olivry says he hopes the results will determine the optimal dose and frequency of this drug for treating canine atopic dermatitis.

“Atopic dermatitis is often treated with antihistamines, but little is known about the absorption and distribution of these drugs in dogs,” Olivry says.

“This lack of knowledge can lead to dogs receiving inappropriate dosages of the drug or incorrect frequency, causing treatment to fail. Some drugs can also cause adverse side effects.”

Karen Helton-Rhodes, DVM, Dipl. ACVD, of Riverdale Veterinary Dermatology and Veterinary Referral Centre, Little Falls, N.J., notes that classic antihistamine therapy (Benadryl, Chlortrimeton, hydroxyzine, Allegra, Claritin) has typically yielded less than optimal clinical results in many canine and feline patients.

This may be due to lack of knowledge regarding appropriate pharmacological dose or a difference in the immunopathology of allergic dermatitis in animals versus people.

This has led many dermatologists to explore less-conventional medications to help control severe symptoms of allergic dermatitis.

Medications that affect serotonin (fluoxetine and doexpin) as well as drugs that alter neuropathic pruritus (gabapentin) and obsessive compulsive disorders (Elavil) are being trialed in clinical patients.

One of the most effective oral medications so far, she says, is cyclosporine (Atopica by Novartis). Atopica is being used in both dogs and cats in many diseases as well as allergic dermatitis. 


 Preliminary results with the allergen-specific immunotherapy
research are very encouraging.

~ Thierry Olivry, DrVet, Ph.D., North Carolina State University ~


Rush Immunotherapy

Rush immunotherapy is another form of treatment piquing veterinary interest.

In 2004, a double-blinded, randomized study was conducted by Ralf Mueller, DrMedVet, Colorado State University, to determine its success rate in canine atopic dermatitis.

Dr. Mueller wanted to compare rush immunotherapy to conventional immunotherapy, and to assess whether rush immunotherapy leads to a quicker reduction in clinical signs than conventional immunotherapy. A Tukey–Kramer multiple comparison test determined the differences between the total scores in 22 dogs at the beginning of the study and at the various time points reached significance after three months. An improvement of more than 50 percent in pruritus was noted in six of 11 dogs in the rush group.

“The current evidence does not support the use of rush immunotherapy compared to traditional protocols,” Olivry says. “In the single clinical study that compared the two protocols, the time to reach noticeable (50 percent or maximal) improvement and the percentage of dogs reaching such improvement were not significant between groups. Further studies are needed.”

Though rush immunology treatment is a hopeful treatment upgrade, some veterinarians advise against the treatment because of its possible side effects.

Dr. Helton-Rhodes says rush immunotherapy allows a rapid introduction of specific allergens in a controlled hospital environment and alleviates the owner’s responsibility of administering the initial injection series, which takes approximately four weeks.

“This process is best suited for clients that have limited time to perform the initial injection series,” Helton-Rhodes says. “I rarely offer this option to my clients due to inherent risks with the rapid induction of allergens, primarily anaphylaxis.

“Also, the overall response time is not typically changed since I often see a clinical response in an average of six months with the conventional protocol.”

Current Treatments

Helton-Rhodes says considering the current thought that canine and feline patients experience percutaneous absorption of allergens, bathing helps to mechanically remove offending allergens and thus lower the antigen load.

“Canine allergy patients have an altered epidermal barrier function which tends to predispose to an increase in bacterial infections and yeast overgrowth,” Helton-Rhodes says. “Shampoos can help decrease the allergen contact and provide soothing relief via medications and are often used in conjunction with oral therapy.”

Topicals with tacrolimus are useful anti-inflammatory agents, while shampoos with phytosphingosine help prevent bacterial infections.

Genesis topical spray, an FDA-approved steroidal spray distributed by Virbac AH Inc., is indicated for the control of pruritus associated with allergic dermatitis in dogs and contains only 0.015 percent triamcinolone acetonide.

Cyclosporine A, which is found in Atopica by Novartis, is the newest oral medication developed for the treatment of atopic dermatitis. It has been proven effective in relieving symptoms without the long-term side effects of steroid use.

Atopica is an FDA-approved non-steroid capsule gaining popularity for long-term allergy treatment. It targets cells in the immune system causing an allergic reaction.

“Atopica is the veterinary form of cyclosporine, a selective immunomodulator,” Helton-Rhodes says. “It is a cyclic polypeptide consisting of 11 amino acids which acts specifically on T-lymphocytes and inhibits the antigen-triggered release of lymphokines by activated T-cells. Cyclosporine has anti-inflammatory and anti-pruritic activities in atopic dermatitis.”

Linda Frank, DVM, Dipl. ACVD, a professor at the University of Tennessee, agrees that Atopica is useful but has concerns.

“Atopica can become very costly,” Dr. Frank says. “I prescribe the tablets to small dogs and cats mostly. I’m more likely going to be prescribing prednisone to large dogs since Atopica can cost $300 a month.”

Frank says about 14.4 percent of the canine population suffers from atopic allergies, second only to flea allergies. Dogs are seen by veterinary dermatologists and immunologists 8 to 1.

“Cats are a little different immunologically,” Helton-Rhodes says. “Many are treated with steroids and aren’t referred at the same frequency as dogs. However, we are starting to see a steady incline of feline patients at our office in New Jersey. While Atopica is not FDA approved for cats, it is often very effective.”

Helton-Rhodes mentioned two products on the horizon that may offer another therapeutic option.

Imulan BioTherapeutics LLC in Scottsdale, Ariz., is trialing a T-helper cell immune modulator for refractory canine allergic dermatitis.

Velcera Inc. in Yardley, Pa., is also conducting studies on a non-steroidal oral mist (exact product/medication not released by the company), that is promoted to be effective as a maintenance medication after the clinical signs of allergy have been alleviated by corticosteroids. Both are still being evaluated.

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