Michael R. Stegemann

A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis

Background Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Preliminary study results suggest that oclacitinib, a selective Janus kinase inhibitor, could reduce pruritus and associated inflammatory skin lesions in dogs with AD. Hypothesis/Objectives The objective was to evaluate efficacy and safety of oclacitinib (Apoquel®) for the control of AD in a randomized, double‐blind, placebo‐controlled trial. Animals Clinicians at 18 specialty clinics enrolled client‐owned dogs (n = 299) with a history of chronic AD. Methods Dogs were randomized to receive either oclacitinib (0.4–0.6 mg/kg twice daily for 14 days and then once daily for up to 112 days) or an excipient‐matched placebo. Owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 7, 14, 28, 56, 84 and 112. Clinicians assessed Canine AD Extent and Severity Index (CADESI‐02) scores on days 0, 14, 28, 56, 84 and 112. Results On days 1, 2, 7, 14 and 28, oclacitinib‐treated dogs had a 29.5, 42.3, 61.5, 66.7 and 47.4% reduction from baseline in owner‐assessed pruritus scores, respectively, compared with a 6.5, 9.1, 6.5, 3.9 and 10.4% reduction in placebo‐treated dogs. On days 14 and 28, dermatologists recorded a 48.4% reduction in CADESI‐02 scores in oclacitinib‐treated dogs compared with a 1.7% reduction and a 3.6% increase in placebo‐treated dogs. After day 28, >86% of all placebo‐treated dogs had moved to an open‐label study, making between‐group comparisons biased. Differences were significant at all time points assessed (P < 0.0001). Conclusions and clinical importance Oclacitinib provided rapid, effective and safe control of AD, with substantial improvement in VAS and CADESI‐02 scores.

Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis.

Background Oclacitinib (Apoquel®) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity. Oclacitinib selectively inhibits Janus kinase 1. Hypothesis/Objectives We aimed to evaluate the safety and efficacy of oclacitinib for the control of pruritus associated with allergic dermatitis in a randomized, double-blinded, placebo-controlled trial. Methods Client-owned dogs (n = 436) with moderate to severe owner-assessed pruritus and a presumptive diagnosis of allergic dermatitis were enrolled. Dogs were randomized to either oclacitinib at 0.4–0.6 mg/kg orally twice daily or an excipient-matched placebo. An enhanced 10 cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days. Results Pretreatment owner and veterinary VAS scores were similar for the two treatment groups. Oclacitinib produced a rapid onset of efficacy within 24 h. Mean oclacitinib Owner Pruritus VAS scores were significantly better than placebo scores (P < 0.0001) on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib Veterinarian Dermatitis VAS scores were also significantly better (P < 0.0001) than placebo scores. Diarrhoea and vomiting were reported with similar frequency in both groups. Conclusions and clinical importance In this study, oclacitinib provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with owners and veterinarians noting substantial improvements in pruritus and dermatitis VAS scores.

A blinded, randomized clinical trial comparing the efficacy and safety of oclacitinib and ciclosporin for the control of atopic dermatitis in client-owned dogs.

Background Ciclosporin is approved for the treatment of atopic dermatitis (AD) in dogs and has been shown to be safe and effective. Placebo-controlled studies suggest that oclacitinib is a safe and effective alternative therapy. Hypothesis/Objectives To evaluate the efficacy and safety of oclacitinib, in comparison to ciclosporin, for the control of AD in a blinded, randomized clinical trial, incorporating a noninferiority test at day 28. Animals A total of 226 client-owned dogs with a history of AD from eight sites were enrolled. Methods Enrolled animals were randomized to receive oral oclacitinib (0.4–0.6 mg/kg twice daily for 14 days, then once daily) or oral ciclosporin (3.2–6.6 mg/kg once daily) for 12 weeks. Owners assessed pruritus using an enhanced visual analog scale (VAS), and veterinarians assessed dermatitis using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-02. Results On days 1, 2, 7, 14, 28, 56 and 84, the percentage reduction from baseline for owner-assessed pruritus changed from 25.6 to 61.0% in the oclacitinib group compared with 6.5 to 61.5% in the ciclosporin group; differences were significant at all time points up to day 28. On day 56, ciclosporin-treated dogs showed a similar decrease in pruritus to oclacitinib-treated dogs. On day 14, the percentage reduction from baseline CADESI-02 was significantly greater in the oclacitinib group (58.7%) than in the ciclosporin group (43.0%). Three times as many adverse events attributed to gastrointestinal signs were reported in the ciclosporin group compared with the oclacitinib group. Conclusions and clinical importance In this study of treatment for canine AD, oclacitinib had a faster onset of action and a lower frequency of gastrointestinal side effects compared with ciclosporin.

Efficacy and safety of cefovecin in treating bacterial folliculitis, abscesses, or infected wounds in dogs

OBJECTIVE To evaluate the efficacy and safety of administration of cefovecin, compared with cefadroxil, for treatment of naturally occurring secondary superficial pyoderma, abscesses, and infected wounds in dogs. DESIGN Multicenter, randomized, positive-controlled clinical trial. ANIMALS 235 client-owned dogs. PROCEDURES Dogs with clinical signs of skin infection confirmed via bacteriologic culture were randomly allocated to receive a single SC injection of cefovecin (8 mg/kg [3.6 mg/lb]) followed by placebo administered PO twice daily for 14 days or cefadroxil (22 mg/kg [10 mg/lb]) administered PO twice daily for 14 days following a placebo injection. Two 14-day treatment courses were permitted. Treatment success was defined as reduction of clinical signs to mild or absent at the final assessment. RESULTS Clinical efficacy achieved with cefovecin in dogs was equivalent to that observed with cefadroxil. At the final assessment, 14 days following the completion of treatment (on day 28 or 42), 92.4% (109/118) of the cefovecin group and 92.3% (108/117) of the cefadroxil group were treatment successes. There were no serious adverse events or deaths related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE A single cefovecin injection (8 mg/kg) administered SC, which could be repeated once after 14 days, was safe and effective against naturally occurring skin infections in dogs and as effective as cefadroxil administered PO twice daily for 14 or 28 days.

Efficacy of oclacitinib (Apoquel®) compared with prednisolone for the control of pruritus and clinical signs associated with allergic dermatitis in client‐owned dogs in Australia

Background Oral glucocorticoids are widely used to reduce pruritus and dermatitis associated with allergic dermatitis. Data suggest that oclacitinib, a Janus kinase inhibitor, is a safe and effective alternative. Hypothesis/Objectives To evaluate the efficacy and safety of oclacitinib compared with prednisolone for the control of pruritus associated with allergic dermatitis in a single-masked, controlled clinical trial with a randomized complete block design. Animals Client-owned dogs (n = 123) with a presumptive diagnosis of allergic dermatitis and moderate to severe pruritus as assessed by the pet owner were enrolled. Methods Dogs were randomized to treatment with either oclacitinib (0.4–0.6 mg/kg orally twice daily for 14 days, then once daily) or prednisolone (0.5–1.0 mg/kg once daily for 6 days, then every other day) for 28 days. An enhanced visual analog scale (VAS) was used by owners to assess pruritus and by veterinarians to assess dermatitis, at all time points assessed. Results Both treatments produced a rapid onset of efficacy within 4 h. The mean reductions in pruritus and dermatitis scores were not significantly different between the treatments except on day 14, when reductions were more pronounced for oclacitinib than prednisolone (P = 0.0193 for owner pruritus scores; P = 0.0252 for veterinarian dermatitis scores). Adverse events were reported with similar frequency in both groups. Conclusion and clinical importance In this study, both oclacitinib and prednisolone provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with substantial improvement in pruritus, reported by owners, and dermatitis, reported by veterinarians.

Effectiveness and safety of cefovecin sodium, an extended-spectrum injectable cephalosporin, in the treatment of cats with abscesses and infected wounds.

OBJECTIVE To evaluate the effectiveness and safety of cefovecin sodium in the treatment of cats with naturally occurring skin infections (abscesses and infected wounds). DESIGN Multicenter (26 sites), randomized, double-blind, controlled clinical trial. ANIMALS Client-owned cats of any breed with naturally occurring skin infections with associated clinical signs and confirmatory bacteriologic culture results. PROCEDURES Cats with clinical signs of skin and soft tissue infection were randomly allocated to receive a single dose of cefovecin (8 mg/kg [3.6 mg/lb], SC) followed by placebo drops administered orally once daily for 14 days or 1 SC placebo injection followed by cefadroxil (22 mg/kg [10 mg/lb], PO, once daily for 14 days). Only one 14-day treatment course was permitted. RESULTS Effectiveness of cefovecin in the treatment of cats with abscesses and infected wounds was similar to that of cefadroxil. At the final assessment on day 28, 97% (86/89) of cefovecin-treated cats and 91% (80/88) of cefadroxil-treated cats were considered treatment successes. There were no serious adverse events or deaths related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE 1 SC injection of 8 mg of cefovecin/kg for the treatment of cats with naturally occurring skin infections (wounds and abscesses) was safe and as effective as cefadroxil administered orally at 22 mg/kg, once daily for 14 days.

Comparative efficacy of tulathromycin and tildipirosin for the treatment of experimental Mycoplasma bovis infection in calves

Abstract The objective of this negative controlled, blinded, randomised, parallel group study was to compare the efficacy of two injectable macrolide antimicrobials, tulathromycin and tildipirosin, administered by single subcutaneous injection at dose rates of 2.5 and 4.0 mg kg−1 bodyweight, respectively, in the treatment of an experimentally induced Mycoplasma bovis infection in calves. A total of 238 M. bovis‐negative calves were challenged on three consecutive days with M. bovis by endobronchial deposition. Post‐challenge, a total of 126 animals fulfilled the inclusion criteria and were randomly allocated to three treatment groups: tulathromycin, tildipirosin and saline. Clinical observations for signs of respiratory disease and injection site assessments were conducted daily for 14 days post‐treatment. The animals were then killed, the lungs were examined for evidence of lesions, and samples collected for bacterial isolation. Calves treated with tulathromycin had a lower percentage of lung with lesions (P = 0.0079), lower mortality (P = 0.0477), fewer days with depressed demeanour (P = 0.0486) and higher body weight (P = 0.0112) than calves administered tildipirosin.