Recombinant human interferon-α14 for the treatment of canine allergic pruritic disease in eight dogs

Abstract

Background: Allergic pruritic diseases are increasingly common in dogs. This group of conditions hampers life quality as pruritus progressively interferes with normal behaviours. Therefore, new treatment modalities for canine allergic pruritic diseases are necessary. While novel drugs have recently reached the market, there is still the need for other therapeutic approaches. Some dogs are refractory even to the newer compounds, and cost is also an important issue for these. Older therapeutic modalities are only moderately successful or have considerable secondary effects, as is the case with glucocorticoids.

Objectives: Report on the use of recombinant human interferon-α14 (rhIFN-α14) for the treatment of canine allergic pruritus. Following the experience with a similar compound in the Japanese market, it was expected that rhIFN-α14 could alter the Th1/Th2 disbalance that drives these diseases.

Methods: Here, we present an uncontrolled trial in which eight dogs with clinical diagnosis of allergic pruritus were treated with rhIFN-α14, either orally or via subcutaneous injections. Skin condition, microbiota and anti-interferon antibody levels were assessed.

Results: The parenteral use of interferon induced hypersensitivity in two of the three dogs in which it was used. The oral administration was consistently safe and could reduce signs of the allergic condition in three of the five treated animals. Treatment also altered the skin microbiota, as verified by next-generation sequencing.

Conclusion: The present results indicate that rhIFN-α14 is a viable candidate for the treatment of canine allergic pruritus. Future controlled studies are needed, and the oral route is indicated for further trials.

Keywords: allergic; atopic dermatitis; dog; interferon; pruritic diseases.

FIGURE 1

Experimental layout and number of animals [in brackets] in each stage. During the enrolment phase the number of candidate dogs was reduced as they fell into the exclusion criteria. Dog 8 was not considered in the efficacy analyses as it left the trial following a single dose of interferon

FIGURE 2

Subjective pruritus score by owners. Results were normalised in relation to the score of each dog at the beginning of the trial. There are 3 bars for each dog, indicating the beginning, the middle and the end of the trial. Dates for these periods are approximated between dogs, since many owners did not comply with the determined evaluation dates. Data are reported as fractions from the start of the trial for each dog. Dogs 4, 5 and 8 received the drug by the parenteral route. The third bar is missing from dog 4 as it left the trial by the 3rd week. Dog 8 is missing as it left the trial following the first dose

FIGURE 3

Veterinarian evaluation scores. (a) Data from the summation of scores for excoriation, erythema and alopecia. There are three bars for each dog, indicating the beginning, the middle and the end of the trial. Dates for these periods are approximated between dogs, since many owners did not comply with the determined evaluation dates. Data are reported as fractions from the start of the trial for each dog. Dogs 4, 5 and 8 received the drug by the parenteral route. The third bar is missing from dog 4 as it left the trial by the 3rd week. Dog 8 is missing as it left the trial following the first dose

FIGURE 4

ELISA for detection of canine anti‐rhIFNα14 antibodies. Top: antibody titers by treatment week. Each line represents an animal. No statistical analysis was performed because there are missing data. Below: antibody titres were grouped for statistical comparisons. For the comparison between injectable and oral treatments, titres at D0 were removed from the analysis as the goal was to assess the induction of anti‐antibodies following treatment. Statistical analysis by two‐tailed Mann‐Whitney test. In the timeline analysis, geometric means are shown. In the aggregated analysis, each dot is a blood collection point

FIGURE 5

Analysis of the skin microbiota. (a) Overall similarity of the skin microbiota between dogs at the start of the trial and at the end. Dog 5 showed very distinctive trends regarding its microbial skin composition. It finished the trial with over 90% of the skin microbiota composed of Staphylococcus. (b) Microbiota richness at the start of the trial versus the end of the test. Chao1 and OTU richness evaluations are shown. Statistical analysis by Mann‐Whitney test. ‘D0’, beginning of the trial with interferon. ‘End’, finalization of the trial