By Jon D. Plant, DVM, Dipl. ACVD
Long before I developed regionally-specific immunotherapy (RESPIT), I was interested in studying the efficacy of allergen-specific immunotherapy (ASIT) in dogs. Why? The only placebo controlled study on ASIT, although a noble effort, had some serious limitations.1 First, there were no validated outcome measures available to the investigators at the time. Ad hoc pruritus scores (0-9) and lesion scores (0-8) were combined into a single score. Whether or not the investigators accurately captured what they were trying to measure cannot be known.
Medications for the control of secondary infection were not permitted. And most importantly, there was no intent-to-treat (ITT) analysis performed. By the time (15 months) that a significant difference in clinical scores was found between the groups, only 5/24 dogs remained in the placebo group and 11/27 dogs remained in the treatment group. ITT analysis, whereby the last score of cases that dropped out is carried forward, may have led to a different conclusion. Those that failed to respond would seem to be the most likely to have dropped out, so this is a significant flaw.
By 24 months, 5 dogs in the placebo group would be characterized as 100% improved at some point in the trial. This study also utilized a form of allergens (with an aluminum adjuvant) not generally used in the United States, where we use aqueous allergens in canine subcutaneous immunotherapy. So when dermatologists in the US cite this study as proof of what they are doing, that is taking some liberty.
I don’t mean to pick on this report, because it is the best that we have. It nicely illustrates, however, the challenge we face in trying to study immunotherapy. We’ve had to take some steps back before we could proceed. I have gone through multiple fits and starts trying to design an immunotherapy study myself. One difficulty has now been surmounted. We have validated methods for scoring canine pruritus and lesions in atopic dermatitis. But even the first validated lesion scoring system (CADESI-03) was so cumbersome (248 evaluations per dog) that it prompted me to develop a more rapid scoring system (CADLI) rather than begin an immunotherapy study with the CADESI-03.2,3 The International Committee on Atopic Diseases of Animals, on which I serve, is still working on a medication scoring system that would allow us to provide and account for much needed concurrent treatment during lengthy atopic dermatitis clinical trials.
Do we need more studies on ASIT? I think so. There is a good bit of variability in how veterinary dermatologists perform and interpret intradermal tests, which is bound to affect immunotherapy prescriptions.4 There is no consensus among us as to which serum allergy test (SAT) is more accurate (VARL Liquid Gold with lots of positive reactions in general, Heksa’s Allercept with few positive reactions and more altogether negative tests, Idexx/Greer’s Aller-g-complete with a medium number of positive reactions, or one of the other laboratories). Some dermatologists claim that IDT-based immunotherapy is more effective than SAT-based immunotherapy, while the 2010 Practice Guidelines of the ITFCAD (the ICADA precursor) states that either can be used as there is no strong evidence supporting one method over the other.5
The bottom line is that studying immunotherapy is difficult, but we are slowly getting the necessary tools in place to design more meaningful studies in the future.
1. Willemse A, Van den Brom WE, Rijnberk A. Effect of hyposensitization on atopic dermatitis in dogs. J Am Vet Med Assoc 1984;184:1277-1280.
2. Olivry T, Marsella R, Iwasaki T, et al. Validation of CADESI-03, a severity scale for clinical trials enrolling dogs with atopic dermatitis. Vet Dermatol 2007;18:78-86.
3. Plant JD, Gortel K, Kovalik M, et al. Development and validation of the Canine Atopic Dermatitis Lesion Index, a scale for the rapid scoring of lesion severity in canine atopic dermatitis. Vet Dermatol 2012;23:515-e103.
4. Hensel P. Differences in allergy skin testing among dermatologists within the same geographical region in the USA. Abstracts of the 7th World Congress of Veterinary Dermatology. July 24-28, 2012. Vancouver, Canada. Vet Dermatol 2012;23 Suppl 1:60.
5. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol 2010;21:233-248.