The effect of pegbovigrastim on early-lactation disease, production, and reproduction in dairy cows.

The objective of this randomized, double-blind, controlled trial was to evaluate the effect of pegbovigrastim (pegylated recombinant bovine granulocyte colony-stimulating factor) on early-lactation disease, milk yield, and reproduction on commercial dairy farms. A total of 1,607 Holstein cows from 6 farms in Ontario and Québec, Canada, were randomly assigned to receive two 2.7-mL subcutaneous injections of either 15 mg of pegbovigrastim (n = 798; Imrestor, Elanco) or sterile physiological saline (placebo; n = 809). The first injection was administered by investigators 1 wk before expected calving, and the second by farm personnel within 24 h after calving, according to the product label. Producers inspected cows daily and using standardized disease definitions, recorded cases of retained placenta, metritis, displaced abomasum, and clinical mastitis until 63 d in milk. Progesterone concentration was measured in serum at wk 3, 5, 7, and 9 postpartum. Cows were examined for purulent vaginal discharge using the Metricheck (Simcro) device and endometritis using the cytobrush method at wk 5 postpartum. Milk production and reproduction data were obtained from farm management software and the national milk recording database. Disease and culling outcomes were assessed with logistic regression, milk production with linear regression, and time-to-event outcomes with proportional hazards regression. All analyses considered parity and pre-treatment body condition score and their interaction with treatment, and accounted for clustering of cows within farm. In a subset of 246 cows, the effect of treatment on metabolic markers (serum concentrations of glucose, ß-hydroxybutyrate, nonesterified fatty acids, cholesterol, haptoglobin, albumin, and calcium) was assessed in wk 1 and 2 postpartum. Pegbovigrastim had no significant effects on the incidence of retained placenta, metritis, displaced abomasum, clinical or subclinical mastitis, purulent vaginal discharge, or endometritis. Treatment reduced the serum concentration of glucose, slightly reduced the concentration of albumin, and slightly increased concentrations of ß-hydroxybutyrate and nonesterified fatty acids, with no effect on the other markers. There were no differences between treatments in culling risk, time to first insemination, pregnancy at first insemination, or time to pregnancy. Milk yield over the first 3 test days of lactation was 1.0 kg per day lower in the pegbovigrastim group, although a mechanism for that effect could not be explained through analysis of our data.

The effect of pegbovigrastim on circulating neutrophil count in dairy cattle: A randomized controlled trial.

Previous research in various species has shown that granulocyte-colony stimulating factor stimulates the production and release of neutrophils from bone marrow. The objective of this study was to characterize the effects of polyethylene glycol-bound bovine granulocyte colony-stimulating factor (pegbovigrastim; Imrestor, Elanco) on circulating leukocyte counts. Thirty-four Holstein cows were randomly assigned to receive 2 injections of either physiologic saline (n = 16) or pegbovigrastim (n = 18), 7 days before expected calving (d -7) and within 24 hours after calving (d 0). Cows were sampled at d -7, d -6, d 0, d +1, d +7, and d +21, relative to calving. Only cows for which the interval from the first injection to calving was ≥ 4 d and ≤ 10 d were included, such that the interval (mean ± SD) from first treatment to calving was 6.7 ± 1.9 d. Treatment effects were assessed with mixed linear regression models. After the first injection, neutrophil counts (×109/ L) in pegbovigrastim-treated cows increased from 4.3 (95% CI 3.8 to 4.8) at d -7 to 18.2 (CI 16.3 to 20.3) at d -6 (P < 0.0001). Their counts then decreased from d -6 to d 0, when the second injection was administered, at a rate of -0.31 ×109 neutrophils/L/day (P < 0.0001). After the second injection, neutrophil counts increased from 16.4 (CI 13.7 to 19.6) at d 0 to 32.8 (CI 25.2 to 42.7) at d +1 (P < 0.0001), after which counts decreased at a rate of -3.73 ×109 neutrophils/L/day until d +7 (P < 0.0001). Counts continued to decrease from d +7 to d +21 at a slower rate of -0.43 ×109 neutrophils/L/day (P < 0.0001), until baseline levels were reached. Conversely, in control cows, neutrophil counts were unchanged from d -7 to d -6 (P = 0.86) after the first injection and then decreased from 6.1 (CI 5.0-7.3) at d 0, to 3.2 (CI 2.4-4.2) at d +1 (P < 0.0001) after the second injection. Neutrophil count was greater (P < 0.001) in pegbovigrastim-treated than in control cows at days -6, 0, +1 and +7. Area under the curve (cells ×109/ L per 28 d) for neutrophil counts in the pegbovigrastim group was 429, versus 99 in the control group (P < 0.0001). The response to each injection of pegbovigrastim was additive and consisted of 95% segmented neutrophils, suggesting that the effect of the treatment was to release mature neutrophils from a substantial pool available in the bone marrow. The sustained increase in circulating neutrophil count around the time of calving may contribute to improved health during the peripartum transition period.

A meta-analysis of the milk-production response after anthelmintic treatment in naturally infected adult dairy cows.

Meta-analysis was used to estimate the effects of anthelmintic treatment on milk production in dairy cows. The literature search included peer-reviewed journals (both full articles and abstracts), conference proceedings and theses and included documents written in English, Spanish, French, Portuguese or Italian. The study outcome was defined as the difference in milk production (kg/cow per day) between treated and untreated cows. Random effect meta-analyses were performed on 75 trials published between 1972 and 2002. The combined estimate after controlling for publication bias and/or small-study effect was of 0.35 kg/cow per day. Significant variation among studies was detected and although several variables were associated with the study outcome, they did not significantly reduce the unexplained variability among trials. Trials reporting the use of endectocides had higher milk-production response compared with trials using older anthelmintics. Similarly, whole-herd treatment trials or trials which applied the treatment in mid-lactation or strategically throughout the year had higher response compared with calving or dry-period treatment trials. Trials reporting the results as total 305-day milk production had lower response compared with trials which measured production as daily milk weight. Primiparous cows trials had lower responses compared with multiparous cows trials.