Background -Lokivetmab is an injectable anti-canine-IL-31 monoclonal antibody to treat clinical manifestations of atopic dermatitis (AD) in dogs.Hypothesis/Objectives -To characterize the efficacy and safety of lokivetmab, and to demonstrate its noninferiority to ciclosporin under field conditions. Animals -Dogs with chronic AD (n = 274) were enrolled from 40 practices in Belgium, The Netherlands, France and Germany.Methods -Animals were randomized (1:1) to oral ciclosporin (5 mg/kg/once daily) or monthly injectable lokivetmab (1-3.3 mg/kg) for three months. Eighty one animals that successfully completed the comparative phase were enrolled in a continuation phase receiving lokivetmab for an additional six months. Owners assessed pruritus on a Visual Analog Scale, skin lesions were assessed by veterinary investigators with a Canine AD Extent and Severity Index (CADESI-03) scale. Results -Lokivetmab was noninferior to ciclosporin for pruritus reduction on Day 28 (51.90% versus 43.72%).For Day 28 CADESI-03 percentage reduction, noninferiority of lokivetmab (54.17) versus ciclosporin (56.86%) was not achieved. At none of the time points were mean CADESI-03 scores significantly different between groups. Continued efficacy towards pruritus and lesions was demonstrated in the continuation phase where 76.3% of animals (n = 45) were assessed as 'normal' for pruritus at study end. No abnormal health events associated with lokivetmab were observed during the initial three month phase (142 dogs) or during the subsequent six month phase (81 dogs).Conclusions and clinical importance -Lokivetmab at a minimum monthly dose of 1 mg/kg provided quick onset (within one day) of a lasting effect in reducing pruritus and skin lesions with a good safety profile.

One can imagine two extremes in the chromatographic separation of a complex sample. At one extreme, typified by capillary gas chromatography, a long, highly efficient column of low to moderate selectivity is used to separate a sample into hundreds of peaks. At the other extreme, typified by affinity chromatography, a short, ineffi-

Background -Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-ofconcept study in dogs with AD.Hypothesis/Objectives -The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial.Animals -Clinicians at 15 referral clinics enrolled 211 client owned dogs with a history of chronic AD.Methods -Dogs were randomized to treatment with lokivetmab (0.125, 0.5 or 2.0 mg/kg) or placebo administered subcutaneously once on Day 0. Dog owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42, 49 and 56. Clinicians assessed Canine AD Extent and Severity Index (CADESI-03) scores on days 0, 7, 14, 28, 42 and 56.Results -Treatment with lokivetmab (2 mg/kg) resulted in a greater percentage reduction from baseline in owner assessed pruritus (days 1-49) and clinician assessed CADESI-03 scores (days 7-56) compared to placebo (P < 0.05); differences were achieved in lower dose groups but at later time points and for shorter duration for both owner assessed pruritus (0.5 mg/kg, days 2-35; 0.125 mg/kg, days 7-21) and clinician assessed CADESI-03 scores (0.5 mg/kg and 0.125 mg/kg, Day 14).Conclusions and clinical importance -Lokivetmab (0.5, 2.0 mg/kg) reduced pruritus compared to placebo for at least 1 month. Level and duration of response increased with increasing dose. Further studies are needed to better understand variability in individual responses across a broader population of dogs with AD.

An equation was derived to describe the unusual chromatographic situation In which part of a sample of a pure solute eluted in the column void volume while the remalnder was strongly retained. It was shown that thls behavior was a natural consequence of slow dlffusion or slow adsorption kinetlcs. Klnetic parameters were measured for an affinlty chromatographic system consisting of lmmobliized proteln A and immunoglobulin G. By use of different immoblilzation methods and supports, It was found that diffusion was ratelimiting in some cases whlle adsorption was rate-limiting in others. One hnmobiiization method decreased the adsorption rate constant of protein A by an order of magnitude.The isocratic measurement of the various contributions to band broadening in liquid chromatography has been the subject of many investigations. Although the theory is well-developed (see ref 1 and references therein), the experimental studies are complicated by such factors as extracolumn band broadening (2), errors in statistical moments measurements (3), and the dependence of some terms on the capacity factor, k' (1, 2,4).Another method for obtaining similar kinetic information is suggested by the "split-peak" phenomenon observed by Sportsman et al. on immobilized antibody affinity chromatographic columns (5,6). A sample of pure antigen eluted as two peaks: a nonretained peak and a strongly retained peak. The relative size of the nonretained peak increased as the sample size or flow rate increased. The theoretical basis of this behavior dates back to the work of Giddings and Eyring who pointed out that there is a probability e-kt (where k is the first-order adsorption rate constant and t is the column void time) that a molecule will not adsorb as it passes through a column (7). Since this probability is usually quite small, split peaks are seldom observed. Only Sportsman et al. (6) have attempted to calculate rate constants from such data. They utilized nonlinear elution conditions and plotted the data according to a second-order reversible rate expression. Prior determination of the binding constant was also necessary. The resulting plot showed significant curvature, which was attributed to heterogeneity of the immobilized ligand molecules.Giddings and Eyring (7) and Sportsman et al. (6) examined only the case in which slow adsorption was rate-limiting. In this paper, the theory of Giddings and Eyring for linear elution conditions is expanded to include slow diffusion as well as slow adsorption.To verify this theory, the adsorption of immunoglobulin G (IgG) is examined by use of columns containing protein A immobilized via three different methods. "Normal" behavior of IgG was previously observed on 5-cm columns (8), but it will be seen that split peaks are observed when the length is reduced to 6 mm.Protein A is a 42 OOO molecular weight protein from the cell walls of Staphylococcus aureus (9). It has an elongated structure consisting of four IgG binding sites and a cell wall binding region (10). Rabbit IgG is a 150000 molecular w...

Background Lokivetmab (ZTS‐00103289) is a caninized anti‐canine IL‐31 monoclonal antibody that has demonstrated efficacy in reducing pruritus associated with atopic dermatitis (AD) in dogs in field trials. Hypothesis/Objectives This study evaluated the safety of lokivetmab in a randomized, double blind, placebo‐controlled trial in client owned dogs with AD with minimal restrictions on concomitant medications and co‐morbidities. Animals Clinicians at 14 veterinary clinics enrolled client owned dogs (n = 245) with chronic AD. Methods Dogs were randomized at a 2:1 ratio to receive either lokivetmab (1.0–3.3 mg/kg) or placebo administered subcutaneously on days 0 and 28. Clinicians examined dogs, and collected blood and urine for assessment of clinical pathology and immunogenicity (days 0, 28 and 42). Results There were no immediate hypersensitivity reactions (e.g. wheals, vomiting). Discomfort at administration occurred in 5.1% of dogs and was similar in frequency and severity between lokivetmab‐ and placebo‐treated groups. Pruritus was reported as an adverse event during the study less frequently in the lokivetmab‐treated group (4.9% and 19.3%, respectively); otherwise, adverse events occurred at a similar frequency between treatment groups. There were no clinically important differences between groups in clinical pathology results. Treatment‐induced immunogenicity was found in 2.5% of lokivetmab treated dogs. A wide variety of concomitant medications were used with no clinically apparent adverse interactions. Conclusions and clinical importance Among a diverse population of 162 client owned dogs with a clinical diagnosis of AD, treatment with two monthly doses of lokivetmab was safe, based on observed adverse events and clinical pathology results over a 42 day period.