Demographics

A total of 299 dogs were enrolled (Table 2). Retrievers and terriers were the most common dog breed groups, comprising 23.4% (Labrador retrievers, 15.7%; and golden retrievers, 7.7%) and 12.7% of the study population, respectively.

Assessment of effectiveness

The effectiveness data set for treatment success comprised 264 dogs in the Owner Pruritus VAS data set (133 placebo- and 131 oclacitinib-treated dogs) and 268 dogs in the clinician’s CADESI-02 data set (134 placebo- and 134 oclacitinib-treated dogs). The data sets for other variables assessed changed at each subsequent time point as a result of errors in compliance with the trial and data collection protocols.

Treatment success: Owner Pruritus VAS

Defining treatment success as at least a 2 cm reduction from baseline at the day of assessment, at day 28 the majority of oclacitinib-treated dogs (66.0%) were considered to be a treatment success compared with 4.0% of the placebo-treated dogs (P < 0.0001). The 95% confidence interval was 54–76% for oclacitinib and 1–9% for placebo. After day 28, the percentage of cases that were a treatment success remained constant at 60.3% on day 56, 59.5% on day 84 and 61.3% on day 112 for the oclacitinib-treated group, compared with ≤2.3% of cases for the placebo-treated group.

Table 2. Demographics and baseline visual analog scale (VAS) data

Treatment success: clinician’s CADESI-02

At day 28, 49% of oclacitinib-treated dogs were considered to be a treatment success compared with 4.0% of the placebo-treated dogs (P < 0.0001). The 95% confidence interval was 32–66% for oclacitinib and 1–11% for placebo. After day 28, the percentage of cases that were a treatment success, over the remaining period, remained relatively constant at 55.6% on day 56, 50.4% on day 84 and 56.1% on day 112 for the oclacitinibtreated group, compared with ≤2.3% of cases for the placebo-treated group. Owner Pruritus VAS scores by day of study The mean day 0 Owner Pruritus VAS scores were very similar (P = 0.7315) between the treatment groups (7.8 and 7.7 cm for the oclacitinib-treated dogs and placebotreated dogs, respectively; Figure 1), corresponding to ‘severe itching’ on the enhanced Owner Pruritus VAS score. After 1 day of treatment, there was a 2.3 cm reduction of the least squares means (mean) from the average baseline in the oclacitinib group, while the dogs receiving placebo treatment had a 0.5 cm reduction (Figure 1). By day 14, the mean Owner Pruritus VAS score for the oclacitinib-treated dogs had decreased to 2.6 cm (a 5.2 cm reduction from baseline). In contrast, the pruritus score for the placebo-treated dogs had decreased to 7.4 cm (a 0.3 cm deduction from baseline; Figure 1). At this time (day 14), 102 (76%) placebo-treated dogs withdrew for worsening of clinical condition associated with AD, with the majority (99%) moving to the open-label study, compared with nine (6%) oclacitinib-treated dogs, of which all (100%) moved to the open-label study. For six of the nine oclacitinib-treated dogs moved to the open-label study, a lack of clinical improvement was cited; two dogs were moved for protocol noncompliance and one dog was moved as a result of an unrelated medical or surgical condition. At day 28, the mean pruritus score for the oclacitinib-treated dogs was 4.1 cm (a 3.7 cm reduction from baseline), equating to ‘mild itching’. In contrast, the mean pruritus score for the placebo-treated dogs was 6.9 cm, a 0.8 cm reduction from baseline (Figure 1). The Owner Pruritus VAS scores were significantly lower in the oclacitinib-treated dogs than in the placebo-treated dogs on each day of assessment, beginning with day 1, to day 28 (P < 0.0001).

The mean VAS scores for oclacitinib-treated dogs continued to improve from day 28 to day 112 to a score of 3.2 cm (a 4.6 cm reduction from baseline), although these changes were not significant. For the dogs that moved to the open-label study, the mean Owner Pruritus VAS score was 7.7 cm on the first day that the dog received oclacitinib, similar to the day 0 score for both of the treatment groups in the placebo-controlled study. Following treatment with oclacitinib, the mean pruritus scores were 4.5 cm by day 28 and 3.6 cm by study end at day 112.

Figure 1. Owner Pruritus visual analog scale (VAS) scores by day of study (95% confidence interval).

Clinician CADESI-02 scores by day of study The mean day 0 Clinician CADESI-02 scores were similar (P = 0.3909) for the two treatment groups (62 and 58 for the oclacitinib- and placebo-treated dogs, respectively; Figure 2). At days 14 and 28, the mean CADESI-02 scores for the oclacitinib-treated group had decreased to 32 (a reduction of 30 from baseline), while the mean scores for the placebo-treated group were 57 (a decrease of 1 from baseline) on day 14 and 61 (an increase of 3 from baseline) on day 28 (Figure 2; P < 0.0001). The mean CADESI-02 score continued to improve from day 28 to day 112, with a final score of 26 (a reduction of 36 from baseline), although these changes were not significant. For the dogs that moved to the open-label study from both treatment groups, the mean Clinician CADESI-02 score was 58 on the first day that the dog received oclacitinib, similar to the day 0 CADESI-02 score for both of the treatment groups in the placebo-controlled study. Following treatment with oclacitinib, the mean CADESI- 02 scores were 34 at day 28 and 21 by the end of the study at day 112.

Table 3. Response-to-treatment VAS scores

Response to treatment

The least squares means RTT VAS scores (Table 3) at the end of the study were significantly better following treatment with oclacitinib (owner’s score, 6.8 cm; and clinician’s score, 6.4 cm) compared with placebo (owner’s score, 0.7 cm; and clinician’s score, 1.0 cm; P < 0.0001). At the end of the open-label study, the mean owner’s and clinician’s scores were 7.4 and 7.5 cm, respectively.

Figure 2. Clinician CADESI-02 scores by day of study (95% confidence interval).

Table 5. Adverse reactions, day 0–16

Percentage of dogs with Owner Pruritus VAS and CADESI-02 scores in the range of normal dogs The frequency distributions for dogs with normal CADESI-02 scores recorded at one or more time points posttreatment were better for oclacitinib-treated dogs [n = 69 (46.9%)] than for placebo-treated dogs [n = 11 (8.1%); P < 0.0001]. Likewise, the frequency distributions for dogs with normal Owner Pruritus VAS scores recorded at one or more time points post-treatment were better for oclacitinib-treated dogs [n = 91 (62.3%)] than for placebotreated dogs [n = 5 (3.6%); P < 0.0001].

Safety assessment

The safety assessment was comprised of a summary of the abnormal health events, clinical pathology results and changes in body weight from day 0 to day 112 for both the placebo-controlled and the open-label study. All 299 dogs (147 placebo-treated and 152 oclacitinib-treated), having received one or more doses of either placebo or oclacitinib, were included in the summaries. Table 4 shows the number of dogs enrolled in both the placebocontrolled and the open-label studies, the number of dogs withdrawn prior to completion and the reason for withdrawal.

Abnormal health events

For the safety assessment, three dogs assigned to placebo treatment that inadvertently received oclacitinib for 1 day or more were included in the oclacitinib-treated group safety summaries. One hundred and eight of the 147 placebo-treated dogs withdrew on or before day 16 (day 14 +/- 2), compared with 13 of the 152 oclacitinibtreated dogs; by day 28, only 33 of the 147 placebo-treated dogs (22.4%) remained on study, compared with 148 of the 155 (95.5%) oclacitinib-treated dogs. The majority of the placebo-treated dogs withdrawn prior to day 28 were removed for worsening clinical signs of AD, and most were then enrolled into the open-label study. At the time of the day 112 assessment, only nine placebo-treated dogs remained in the placebo-controlled study. The small number of placebo-treated dogs confounds a between-group comparison of the abnormal health events. Given that the majority of the placebo-treated dogs withdrew before day 16, Table 5 depicts only the direct comparison of adverse events observed in the two treatment groups up to day 16. The diarrhoea, vomiting, anorexia and lethargy spontaneously resolved in 90% of the cases, with the remainder of the cases responsive to supportive care; dosing continued uninterrupted throughout the adverse event.

roughout the adverse event. Between the placebo-controlled and the open-label study, 283 dogs received at least one dose of oclacitinib. The following clinical signs were reported after beginning oclacitinib (expressed as the percentage of dogs with at least one report of the clinical sign as a nonpre-existing finding): pyoderma, 12.0%; nonspecified dermal nodules, 12.0%; otitis, 9.9%; vomiting, 9.2%; diarrhoea, 6.0%; histiocytoma, 3.9%; cystitis, 3.5%; anorexia, 3.2%; lethargy, 2.8%; yeast skin infections, 2.5%; pododermatitis, 2.5%; lipoma, 2.1%; polydipsia, 1.4%; lymphadenopathy, 1.1%; nausea, 1.1%; increased appetite, 1.1%; aggression, 1.1%; and weight loss, 0.7%.

Of the 283 oclacitinib-treated dogs, two (0.7%) were withdrawn from study due to suspected or confirmed malignant neoplasia, including one dog (a 5.5-year-old Labrador retriever) that developed a heart-based mass after 21 days of treatment with oclacitinib, and one (an 11-year-old mixed breed) that developed a Grade III mast cell tumour after 60 days on oclacitinib. In the placebo group, one of 147 dogs developed a Grade I mast cell tumour and was withdrawn from the study. Two other dogs (0.7%) were withdrawn from the study due to suspected treatment-related adverse reactions, including one dog that had an intense flare-up of dermatitis and severe secondary pyoderma after 19 days of oclacitinib administration, and one dog that developed generalized demodicosis after 28 days of oclacitinib administration. Additional dogs were hospitalized for diagnosis and treatment of pneumonia (one dog), transient bloody vomiting and stool (one dog) and cystitis with urolithiasis (one dog). There were few changes in body weight. Placebo-treated dogs lost ~1% of their body weight in the first 28 days of the study, although the remaining placebo-treated dogs then showed a slight weight gain (2.5%) by day 112. Oclacitinib-treated dogs showed an overall weight gain compared with baseline [~4% (-14 to 29%)] by day 112

Haematology, serum chemistry and urinalysis The arithmetic mean (‘mean’) value for all of the haematology and serum chemistry analytes in both treatment groups fell within the laboratory’s normal reference range for that analyte at all of the visits reported during both the placebo-controlled and the open-label studies. While still within the normal reference range, an increase in mean serum cholesterol and mean serum lipase levels and a decrease in mean serum globulin and leukocyte levels were observed. In the oclacitinib-treated group, mean white blood cell, neutrophil, eosinophil and monocyte counts decreased to day 14 (neutrophils and monocytes) or day 28 (white blood cells and eosinophils) and then remained stable. Although mean values remained within the normal range, individual dogs developed leukopenia, primarily due to neutropenia. The mean lymphocyte count increased at day 14 and then returned to baseline. In the oclacitinib-treated dogs, mean serum globulin decreased to day 56 and then remained stable, within the normal range; mean serum cholesterol increased by day 14 and then remained stable, within the normal range; mean serum lipase increased to day 56 and then remained stable, within the normal range. Mean liver enzymes were not affected by administration of oclacitinib maleate. There were no differences in urinalysis, and summaries showed no apparent differences between the placebotreated dogs and the oclacitinib-treated dogs.

Concomitant medications

A wide variety of concomitant medications and therapies were used in conjunction with either placebo or oclacitinib treatment. The concomitant medications administered most often (i.e. in ≥7% of the oclacitinibtreated dogs) are summarized by drug class and treatment group in Table 6. There did not appear to be any drug–drug interactions associated with administration of oclacitinib.

Discussion

Results of the study provide evidence of the effectiveness of oclacitinib for the control of AD, with each of the efficacy variables assessed being significantly (P ≤ 0.0001) better for the oclacitinib-treated dogs than for the placebo-treated dogs. Owner Pruritus VAS treatment success was ~60% or higher for all assessment time points, and the Clinician CADESI-02 success rates were approximately 50% or higher, in contrast to the success rates for placebo. The antipruritic effect was rapid, with owners reporting a mean 29.5% reduction in pruritus in oclacitinib-treated dogs within 24 h compared with only a 6.5% reduction for placebo-treated dogs. By day 14, the reduction in pruritus was 67% with oclacitinib, compared with 3.9% in placebo-treated dogs. The improvement in lesion scores was also rapid, with a 48.4% reduction in CADESI-02 scores (compared with a 1.7% decrease in placebo-treated dogs) after only 14 days of treatment.

Table 6. Concomitant medications and therapies

The improvements in pruritus and lesion scores were maintained for 112 days and replicated in dogs entered into the open-label study. These results are comparable to an earlier randomized placebo-controlled trial18 that reported a 26% reduction in pruritus by 24 h following treatment with 0.4 mg/kg oclacitinib every 12 h. That trial followed dogs for only 14 days, after which there was a 68% reduction in pruritus scores and a 54% reduction in CADESI-02 scores. Three systematic reviews of clinical trials of pharmacological interventions in canine AD concluded that there remains a lack of well-designed randomized clinical trials for the majority of products used in the treatment of AD.8,12,30 The ICADA clinical practice treatment guidelines recommend, among other interventions, the use of glucocorticoids (orally and topically) and ciclosporin for the control of AD.6 In two studies considered high quality,22,31 prednisolone or methylprednisolone administered at recommended label doses resulted in a 45–69% reduction in CADESI scores and a 33–81% reduction in pruritus scores over 14–120 days. In nine randomized clinical trials with a total of 424 dogs,12,30 ciclosporin administered at the recommended label dose resulted in a 39.9–67% reduction in CADESI scores and a 36–78% reduction in pruritus scores over 21–120 days. Additionally, 47– 87.5% of dogs showed a ≥50% reduction in the CADESI scores. The efficacy of oclacitinib therefore appears to be at least as good as that for systemic glucocorticoids and ciclosporin. The efficacy end-points for ciclosporin were from day 21 onwards, which reflects the time needed to see clinical benefit for this drug. Given that there may be a period of time before the full clinical benefit from ciclosporin may be observed, it has been suggested that ciclosporin is co-administered with prednisolone at 1 mg/kg every other day for the first 14 days for dogs with AD.32

In this study, normal was defined as obtaining a CADESI-02 score of ≤15 and a pruritus VAS score of <2 cm. These definitions align with what has been proposed as normal by Olivry et al.28 for CADESI-03 and by Rybnicek et al.29 for the pruritus VAS. The percentage of dogs with lesions and pruritus scores in the range of normal was 46.9 and 62.3%, respectively, for oclacitinib-treated dogs compared with 8.1 and 3.6% for placebo-treated dogs. The most recent systematic review12 summarized the results of three clinical trials, in which the percentage of dogs with lesions in the range of normal dogs and percentage of dogs with pruritus in the range of normal dogs was assessed. In one study,33 hydrocortisone acetate administered topically once daily for 7 days and then every other day resulted in 30% of dogs with lesions in the range of normal dogs and 10% of dogs with pruritus in the range of normal dogs. In another study,34 in which ciclosporin was administered orally at a dose 50–200 mg/day, 25% of dogs were reported with lesions in the range of normal dogs and pruritus was not reported. In a third study, when hydrocortisone acetate applied topically once daily was compared with ciclosporin administered orally once daily at an initial dose of 5 mg/kg, with the frequency decreased to either every other day or twice weekly if effective, hydrocortisone acetate resulted in 33% of dogs with lesions in the range of normal dogs and 42% of dogs with pruritus in the range of normal dogs, compared with 43 and 33%, respectively, for ciclosporin-treated dogs.35 In comparison, in the present study, oclacitinib appears to be equivalent or better than either hydrocortisone acetate or ciclosporin in returning dogs with AD to a normal state. It should be reiterated that the present study was designed and the results analysed to support the registration of oclacitinib. While the selection of the variables to be assessed and the criteria used for the assessment met the rigid standards required to for product approval, they do not always allow for a direct comparison with other randomized clinical trials (e.g. number of dogs exhibiting a 50%/90% reduction of pruritus and CADESI scores).8,9,30

Oclacitinib appeared to be well tolerated, with few differences in the incidence of adverse events between oclacitinib-treated and placebo-treated dogs during the first 2 weeks of treatment. Many of the clinical signs reported here (otitis externa, pyoderma and pododermatitis) are secondary complications of AD and therefore not likely to be associated with oclacitinib administration.36 Although anorexia was reported in four of 152 (2.6%) oclacitinib-treated dogs (and none of the placebo-treated dogs), the anorexia was transient and resolved without treatment. Of note, oclacitinib-treated dogs had a slight weight gain over the course of the study. No comparison between the two treatment groups was possible after 14 days, because most placebo-treated dogs were withdrawn from the study. However, by study end, a total of 283 (of 299) dogs had received at least one dose of oclacitinib, and the reported adverse events do not indicate any specific safety alert associated with oclacitinib treatment. Most of the frequently reported adverse events, such as pyoderma, nonspecific dermal masses, otitis, histiocytoma, yeast skin infections, pododermatitis and lipoma, were related to the skin. Many of these could be related to compromised skin and/or immune function in chronic AD, and it is unlikely that the frequency of adverse events that are directly related to the skin would be different with other AD treatments. A number of gastrointestinal disorders were observed; vomiting in 9.2% and diarrhoea in 6.0% of the 283 oclacitinib-treated dogs. The majority of these cases were of mild or moderate severity, and many resolved in a single day without treatment, with most dogs continuing on oclacitinib therapy for the duration of the study. In a 4 month study, 47% of ciclosporin-treated and 25% of methylprednisolone-treated dogs exhibited gastrointestinal disorders, suggesting that oclacitinib treatment could be better tolerated than both of these common treatments.31

Polydipsia was observed in only 1.4% (four of 283 dogs) of the oclacitinib-treated dogs, and polyuria and polyphagia were not observed at all. In another study of canine AD, 25% of methylprednisolone-treated dogs (n = 59) exhibited polyuria/polydipsia, with 12% showing increased appetite and body weight.31

It is known that inhibiting JAK/STAT signal transduction can affect the activity of selected interleukins, which can interfere with the development, differentiation and function of some leukocyte populations.37 For this reason, bacterial, fungal or parasitic infections were carefully monitored and recorded. Infections and infestations that caused either withdrawal from the study or hospitalization were observed in four oclacitinib-treated dogs, as follows: withdrawal due to severe secondary pyoderma (after 19 days of treatment); withdrawal due to generalized demodicosis (after 28 days of treatment); hospitalization for diagnosis and treatment of pneumonia (after 91 days of treatment); and hospitalization for cystitis secondary to urolithiasis (after 80 days of treatment). All four animals recovered fully. Long-term administration of up to five times the recommended dose for 26 weeks (twice daily for 6 weeks and once daily for 20 weeks) was well tolerated in dogs of 1 year of age in laboratory safety studies, without any indication of secondary bacterial or parasitic infections.38

ns.38 While the clinicians reported a number of nonspecified dermal nodules, virtually all were considered benign. Only two malignant skin tumours, both mast cell tumours, were diagnosed. Mast cell tumours are the most common cutaneous tumour in dogs and occur most frequently in mixed breeds, although Boston terriers have been noted to be at higher risk.39 The equal frequency in the two treatment groups, the high incidence of canine mast cell tumours and the breed predilection suggest it is unlikely that these neoplasms were caused by oclacitinib treatment. The only other potential malignancy, a heart base mass suggestive of a haemangiosarcoma, was observed after only 21 days, and it is hypothesized that this neoplasm was present before oclacitinib treatment started. However, as with any other immunomodulator that may exacerbate neoplastic conditions, dogs treated with oclacitinib should be monitored for the development of neoplasia.40

In the study reported here, two sets of data were analysed; the per protocol data set was used for the assessment of efficacy and the intent-to-treat data set used for the assessment of safety. By definition, an intent-to-treat data set includes all animals that were randomized to study in their respective treatment groups.41,42 In the present study, the intent-to-treat data set was not used for the assessment of efficacy, in that once a dog was withdrawn from study, there were no data available for the time points after the withdrawal. Thus, it was not possible to conduct an intent-to-treat efficacy analysis as has been performed in other randomized clinical trials for AD.8

Recent insight into the pathophysiology of AD, including the most clinically relevant inflammatory mediators and cytokines, suggests that more targeted therapies than those currently available could be developed.4 Oclacitinib represents such a targeted treatment option, as described by Gonzales et al.16 The dosage regimen, aimed for the long-term control of chronic AD, investigated in this study was designed both to maximize the beneficial effects, such as the inhibition of IL-31, and to minimize the T-cell inhibition to avoid any safety concerns, especially with chronic use. The efficacy and safety results of our study suggest that the oclacitinib regimen fulfils both criteria; twice daily dosing for the first 14 days rapidly breaks down the itch–cycle and, as hypothesized,13,19 successfully downregulates some inflammatory, allergic and pruritogenic cytokine activity, and the subsequent once daily dosing, administered as maintenance therapy, provides a solid margin of safety while maintaining efficacy for chronic use, during the time period observed.

Acknowledgements

We would like to thank the following veterinary dermatologists who enrolled dogs in this study and performed the clinical investigations: Glen Burkett, Sarah Colombini Osborn, Kimberly Coyner, Karen Farver, Dunbar Gram, Terry Grieshaber, Craig Griffin, Carolyn Kidney, Allison Kirby, Thomas Lewis, Lindsay McKay, Colleen Mendelsohn, Linda Messinger, Sandra Sargent, Amy Shumaker, Mitchell Song, Laura Stokking and Sheila Torres. The test article (oclacitinib or placebo) was provided at no cost to the clinic, and clinicians were compensated for the costs associated with each dog’s clinic visits. We thank the following current and former Zoetis colleagues for their contributions: Candace A. Sousa, Jessica A. Harfst, Marcia J. Adams, Anne E. Daniels and Nancy L. Savicke.

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Resumé

Contexte – Le prurit est le signe clinique typique de la dermatite atopique (AD) chez le chien. Les resultats d’etudes preliminaires suggerent que l’oclacitinib, un inhibiteur selectif de Janus kinase, pourrait reduire le prurit et les lesions inflammatoires cutanees associees chez les chiens atteints d’AD.

Hypotheses/Objectifs – L’objectif etait d’evaluer l’efficacite et l’innocuite de l’oclacitinib (Apoquel) pour le controle de l’AD dans une ^ etude randomisee, control ^ ee contre placebo, en double aveugle.

Sujets – Les cliniciens de 18 cliniques specialisees ont inclus des chiens de proprietaires (n = 299) atteints de dermatite atopique chronique.

Methodes – Les chiens ont ete randomises pour recevoir soit de l’oclacitinib (0.4 –0.6 mg/kg deux fois par jour pendant 14 jours puis une fois par jour pendant 112 jours) soit un placebo contenant l’excipient. Les proprietaires ont realise desechelles de prurit visuellesa jours 0, 1, 2, 7, 14, 28, 56, 84 et 112.Les cliniciens ont realise des scores CADESI-02 (Canine AD Extent and Severity Index)a jours 0, 14, 28, 56, 84 et 112.

Resultats – Aux jours 1, 2, 7, 14 et 28, les chiens ayant recu de l’oclacitinib avaient respectivement 29.5, 42.3, 61.5, 66.7 et 47.4% de reduction de scores de pruritevalue par les proprietaires comparea 6.5, 9.1, 6.5, 3.9 et 10.4% de diminution chez les chiens controles ayant recu le placebo. A jours 14 et 28, les dermatologues ont enregistre une diminution de 48.4% des scores CADESI-02 chez les chiens recevant del’oclacitinib comparea une diminution de 1.7% et une augmentation de 3.6% chez les chiens recevant le placebo. Apres le jour 28, plus de 86% des chiens recevant le placebo ontete transfere dans uneetude ouverte faisant des biais de comparaison entre les groupes. Les differencesetaient significativesa tous les points evalues ( P < 0.0001).

Conclusions et importance clinique – L’oclacitinib a entraine un contr ole rapide, efficace et s ^ ur de l’AD, ^ avec une amelioration substantielle des scores de l’echelle analogue visuelle et du CADESI-02.

Resumen

Introduccion – el prurito es la signo clınico mas relevante de la dermatitis atopica (AD). Estudios preliminares sugieren que oclacinitib, un inhibidor selectivo de la quinasa Janus, puede reducir el prurito y las lesiones cutaneas inflamatorias asociadas a perros con AD.

Hipotesis/Objetivos – el objetivo fue evaluar la eficacia y seguridad de oclacinitib (Apoquel) para el control de la dermatitis atopica en un a prueba doble ciega al azar controlada con placebo.

Animales – veterinarios clınicos de 18 hospitales especializados reclutaron perros de propietarios particulares (n = 299) con historia de AD cronica.

Metodos – los perros fueron distribuidos al azar para recibir bien oclacitinib (0,4- 0,6 mg/kg dos veces al dıa durante 14 dıas y despues una vez al dıa hasta por 112 dıas) o un placebo con el mismo excipiente. Los propiertarios valoraron en la escala analoga visual el ındice de prurito en los dıas 0, 1, 2, 7, 14, 28, 56, 84 y 112. Los clınicos hicieron lo mismo siguiendo el ındice canino de extension y severidad del prurito (CADE-SI-02) en los dıas 0, 14, 28, 56, 84 y 112.

Resultados – en los dıas 1, 2, 7, 14 y 28 los perros tratados con oclacinitib tuvieron una reduccion del 29,5; 42,3; 61,5; 66,7 y 47,4% con respecto a los valores iniciales en la escala de prurito evaluada por los propietarios, respectivamente. Esto estuvo en contraste con la reduccion en los perros tratados con placebo que fue de 6,5; 9,1; 6,5; 3,9 y 10,4%, respectivamente. En los dıas 14 y 28 los dermatologos notaron una reduccion del 48,4% en los valores de CADESI-02 en los perros tratados con oclacitinib comparado con una reduccion de 1,7% y un aumento de 3,6% en perros tratados con placebo. Despues del dıa 28, >86% de los perros tratados con placebo se pasaron a un estudio abierto, desviando la comparacion entre grupos. Las diferencias fueron significativas en todos los puntos estudiados (P = 0,0001).

Conclusiones e importancia clınica – oclacitinib produjo un control rapido, efectivo y seguro de la AD con mejora sustancial en la escala visual analoga y los valores CADESI-02.

Zusammenfassung

Hintergrund – Juckreiz ist bei Hunden das Kardinalsymptom der atopischen Dermatitis (AD). Vorl€ aufige Studienergebnisse zeigen, dass Oclacitinib, ein selektiver Janus Kirasehemmer, den Juckreiz und damit verbundene entzundliche Hautreaktionen bei Hunden mit AD reduzieren konnte. €

Hypothese/Ziele – Das Ziel dieser Studie war es, die Wirksamkeit und Sicherheit von Oclacitinib (Apoquel) zur Kontrolle von AD in einer randomisierten, doppelblinden, Plazebo-kontrollierten Studie zu evaluieren.

Tiere – KlinikerInnen aus 18 Spezialkliniken nahmen Hunde im Besitz von KundInnen (n = 299) mit der Anamnese einer chronischen AD in die Studie auf.

Methoden – Die Hunde erhielten zuf€ allig entweder Oclacitinib (0,4-0,6 mg/kg zweimal t€ aglich fur 14 Tage € und dann einmal t€ aglich fur bis zu 112 Tage) oder ein dem Tr € € agermedium angepasstes Plazebo. Die BesitzerInnen beurteilten die Juckreiz Werte mittels visueller Analogskala an den Tagen 0, 1, 2, 7, 14, 28, 84 und 112. Die KlinikerInnen beurteilten die Canine AD Extent and Severity Index Werte (CADESI-02) an den Tagen 0, 14, 28, 56, 84 und 112.

Ergebnisse – An den Tagen 1, 2, 7, 14 und 28 zeigten die mit Oclacitinib behandelten Hunde eine 29,5; 42,3; 61,5 bzw 47,4%ige Reduktion der von den BesitzerInnen beurteilten Juckreizwerte im Vergleich zu 6,5; 9,1; 6,5; 3,9 und 10,4%igen Reduktion bei den mit Plazebo behandelten Hunden. An den Tagen 14 und 28 beschrieben die DermatologInnen eine 48,4%ige Reduktion der CADESI-02 Werte bei den mit Oclacitinib behandelten Hunde im Vergleich zu einer 1,7%igen Reduktion und einem 3,6%igen Anstieg bei den mit Plazebo behandelten Hunde. Nach dem Tag 28 waren >86% aller Plazebo-behandelten Hunde in einer offenen Studie, was die Vergleiche zwischen den Gruppen polarisiert. Die Unterschiede waren zu allen Zeitpunkten signifikant verschieden (P<0,0001).

Schlussfolgerungen und klinische Bedeutung – Oclacitinib stellte eine rasche, wirksame und sichere Kontrolle von AD mit einer deutlichen Verbesserung der Werte der visuellen Analogskala und der CADESI- 02 Werte dar.