BackgroundPruritus 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/ObjectivesThe objective was to evaluate efficacy and safety of oclacitinib (Apoquel®) for the control of AD in a randomized, double‐blind, placebo‐controlled trial.AnimalsClinicians at 18 specialty clinics enrolled client‐owned dogs (n = 299) with a history of chronic AD.MethodsDogs 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.ResultsOn 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 importanceOclacitinib provided rapid, effective and safe control of AD, with substantial improvement in VAS and CADESI‐02 scores.

BackgroundPruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL‐31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs.Hypothesis/ObjectivesThe objectives were to characterize an IL‐31‐induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti‐pruritic effects of oclacitinib against those of prednisolone and dexamethasone.AnimalsPurpose‐bred beagle dogs were used in all studies.MethodsRandomized, blinded, placebo‐controlled studies were designed to evaluate and compare the anti‐pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL‐31. Video surveillance was used to monitor and score pruritic behaviours in study animals.ResultsPrednisolone [0.5 mg/kg, per os (p.o.)] reduced IL‐31‐induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL‐31‐induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti‐pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed.Conclusion and clinical importanceThe efficacy of prednisolone, dexamethasone and oclacitinib in the IL‐31‐induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.

Background Frunevetmab, a felinized antinerve growth factor monoclonal antibody, effectively decreases osteoarthritis (OA) pain in cats. Objective To evaluate the efficacy of frunevetmab given at monthly intervals in a randomized, placebo‐controlled, parallel‐group, double‐blind superiority study. Animals Two hundred seventy‐five client‐owned cats with naturally‐occurring OA pain and associated mobility impairment and disability. Methods Randomized, placebo‐controlled, parallel‐group, double‐blind, superiority study. Following screening, cats received frunevetmab (nominal dose of 1.0 mg/kg, SC [effective dose range of 1.0‐2.8 mg/kg]) or placebo on days 0, 28, and 56. Outcome measures were owner questionnaires and veterinary physical and orthopedic evaluations at days 28, 56, and 84. Success/failure rates (and numbers needed treat, NNT) and change in scores (and standardized effect size, ES) were analyzed. Results Frunevetmab (182) and placebo (93) treated cats were enrolled and received at least 1 treatment. Significant improvement with frunevetmab over placebo occurred at days 28 and 56 for the client specific outcome measures (CSOM) questionnaire (success rates and total scores [NNT of 9 and ES of 0.3 at day 56]); at days 28 and 56 for owner‐assessed global treatment response; and at days 56 and 84 for veterinarian‐assessed joint pain (ES of 0.18 at day 56). Adverse events did not differ between groups, except skin disorders which collectively occurred significantly more frequently in frunevetmab treated (32/182 cats) vs placebo (8/93 cats). Conclusions and Clinical Importance Frunevetmab has the potential to address a critical gap in the treatment of pain because of osteoarthritis in cats.

Background: The therapeutic strategy of bovine respiratory disease (BRD) often involves a combination of an antibiotic with an anti-inflammatory agent. Aim of this study was to evaluate the clinical effect of a new combination product containing tulathromycin and ketoprofen for the treatment of naturally occurring BRD. Methods: Two hundred and eighty animals were randomized upon diagnosis of BRD. One hundred forty animals each were treated once subcutaneously with tulathromycin-ketoprofen or tulathromycin. Rectal temperature of each animal was measured at 1, 2, 4, 6, 8, 10, 12 and 24 h post-treatment. Individual respiration and depression scores were determined at 6 h post-treatment. Daily rectal temperature, respiration and depression scores were recorded from day 2 to 14 and on day 21. Results: The tulathromycin-ketoprofen and tulathromycin treatment group demonstrated a treatment success rate of 94.2% and 95.0%, respectively and a relapse rate of 3.8% and 4.0%, respectively. Tulathromycin-ketoprofen demonstrated superior pyrexia control compared to tulathromycin within the first 24 h following treatment. Tulathromycin-ketoprofen-treated animals demonstrated faster improvement of their clinical symptoms (respiration and depression score). Conclusion: Efficacy of tulathromycin-ketoprofen for the treatment of BRD was non-inferior to tulathromycin. The combination product clearly exhibited more pronounced fever control than tulathromycin which is considered beneficial for animal welfare.

The current studies aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to establish a PK‐PD model for ketoprofen in a new fixed combination product containing tulathromycin (2.5 mg/kg) and ketoprofen (3 mg/kg) to treat bovine respiratory disease associated with pyrexia in cattle. Firstly, the effect of different ketoprofen doses as mono‐substance (1, 3, and 6 mg/kg subcutaneous) on lipopolysaccharide‐induced fever was evaluated which indicated that rectal temperature reduction lasted longer in the calves receiving 3 and 6 mg/kg ketoprofen. Secondly, the PK profile of the combination product was compared with mono‐substance products (3 mg/kg subcutaneous and intramuscular). The PK profile of ketoprofen in the combination product was characterized by longer t1/2, lower Cmax and increased AUC in comparison with mono‐substance products. Due to prolonged ketoprofen exposure in the combination product, the pyrexia reducing effect of the combination product lasted longer in a second lipopolysaccharide challenge study in comparison with mono‐substance products. Finally, a PK‐PD model for the anti‐pyretic effect of ketoprofen was developed based on the data from the different studies. The PK‐PD model eliminated the need for additional animal experiments and indicated that a 3 mg/kg ketoprofen dose in the combination product provided optimal efficacy.

Lameness in dairy cattle decreases productivity and diminishes animal welfare. Alleviating the pain associated with lameness would improve animal welfare and could improve productivity and enhance recovery. In dairy cows, lameness is associated with increased duration and frequency of lying bouts, abnormal locomotion, and increased weight shifting behavior. Weight shifting between the rear limbs can be used to objectively quantify pain levels and responses to pain-relieving drugs. The hypothesis of this study was that administration of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen would decrease pain-associated behaviors in lame dairy cows.