Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs.

OBJECTIVE: To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA). ANIMALS: 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months' follow-up after starting leflunomide. METHODS: Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. RESULTS: Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. CLINICAL RELEVANCE: Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

Increased risk of select glucocorticoid adverse events in dogs of higher body weight.

There are limited data on glucocorticoid treatment in dogs. The purpose of this study was to investigate whether dogs of higher body weight experienced more adverse events when receiving glucocorticoid therapy. Data pertaining to glucocorticoid therapy was abstracted from the records of 61 dogs that were prescribed glucocorticoids for treatment of immune-mediated thrombocytopenia or hemolytic anemia from 2014 to 2019. The odds of developing muscle atrophy and polyphagia during therapy were increased by 30% for each 5 kg of additional body weight. Almost half of the dogs (44.3%) fluctuated > 15% from baseline weight during therapy. Dogs whose body condition scored as above ideal were at increased risk (odds ratio = 4.2) for being diagnosed with urinary tract infection. Our findings suggest that standard linear glucocorticoid dosing may place higher body weight dogs at increased risk of developing adverse events. Accelerated glucocorticoid tapering and/or alternative dosing schemes in dogs with higher body weights may be prudent in efforts to improve tolerance and client compliance.

Risque accru d'événements indésirables liés aux glucocorticoïdes chez les chiens de poids corporel plus élevé. Les données sur le traitement par glucocorticoïdes chez le chien sont limitées. Le but de cette étude était de déterminer si les chiens de poids corporel plus élevé présentaient plus d'événements indésirables lorsqu'ils recevaient un traitement par glucocorticoïdes. Les données relatives au traitement par glucocorticoïdes ont été extraites des dossiers de 61 chiens auxquels des glucocorticoïdes ont été prescrits pour le traitement d'une thrombocytopénie à médiation immunitaire ou d'anémie hémolytique de 2014 à 2019. Les risques de développer une atrophie musculaire et une polyphagie pendant le traitement ont augmenté de 30 % pour chaque 5 kg de poids corporel supplémentaire. Près de la moitié des chiens (44,3 %) ont fluctué > 15 % par rapport au poids de base pendant le traitement. Les chiens dont l'état corporel était supérieur à l'idéal présentaient un risque accru (rapport de cotes = 4,2) de recevoir un diagnostic d'infection des voies urinaires. Nos résultats suggèrent que le dosage linéaire standard de glucocorticoïdes peut exposer les chiens de poids corporel plus élevé à un risque accru de développer des événements indésirables. Une diminution accélérée des glucocorticoïdes et/ou des schémas posologiques alternatifs chez les chiens ayant un poids corporel plus élevé peuvent être avisés dans les efforts visant à améliorer la tolérance et l'observance du client.(Traduit par Dr Serge Messier).

Outcomes for dogs with functional thyroid tumors treated by surgical excision alone.

OBJECTIVE: To describe clinical findings and survival times for dogs with functional thyroid tumors treated with surgery alone and investigate potential prognostic factors for outcome in these patients. ANIMALS: 27 client-owned dogs. PROCEDURES: Medical records of 9 institutions were reviewed to identify dogs with hyperthyroidism secondary to thyroid neoplasia that were treated with surgery alone between 2005 and 2015. Data collected included signalment, hematologic and physical examination findings, tumor staging results, time from diagnosis to treatment, surgical procedure performed, histologic findings, evidence of recurrence or metastatic disease, and date of death or last follow-up. Median survival time and 1-, 2-, and 3-year survival rates were assessed by Kaplan-Meier analysis. Associations between variables of interest and the outcome of death were assessed with Cox proportional hazards models. RESULTS: Dogs from 8 institutions met inclusion criteria. Median age at diagnosis was 10 years (range, 8 to 13 years). Golden Retrievers and Labrador Retrievers were commonly represented (5 dogs each). Polyuria with polydipsia (15/27 [56%]) and weight loss (12 [44%]) were the most common clinical signs; 2 dogs without clinical signs had hyperthyroidism identified by routine hematologic analysis. One dog had metastatic disease at the time of diagnosis. Most tumors (23/27 [85%]) were malignant. Estimated median survival time was 1,072 days. No significant prognostic factors were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with resectable functional thyroid tumors had a good prognosis with surgical excision alone. Survival times for these dogs were similar to those in previous studies that included dogs with nonfunctional thyroid tumors.

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL).

Evaluation of local toxic effects and outcomes for dogs undergoing marginal tumor excision with intralesional cisplatin-impregnated bead placement for treatment of soft tissue sarcomas: 62 cases (2009-2012).

OBJECTIVE To evaluate outcomes for dogs following marginal tumor excision and intralesional placement of cisplatin-impregnated beads for the treatment of cutaneous or subcutaneous soft tissue sarcomas (STSs) and assess local toxic effects of cisplatin-impregnated beads in these patients. DESIGN Retrospective case series. ANIMALS 62 client-owned dogs. PROCEDURES Medical records were reviewed to identify dogs with STSs treated with marginal excision and intralesional placement of cisplatin-impregnated beads. Patient signalment; tumor location, type, and grade; dates of tumor resection and bead placement; number of beads placed; and concurrent treatments were recorded. Data regarding toxicosis at the bead site (up to the time of suture removal) and tumor recurrence were collected; variables of interest were evaluated for associations with these outcomes, and systemic adverse effects (if any) were recorded. RESULTS 24 of 51 (47%) evaluated dogs had toxicosis at bead placement sites (classified as mild [n = 12] or moderate [10] in most). Fifteen of 51 (29%) tumors recurred. Median disease-free interval was not reached for dogs with grade 1 and 2 STSs, whereas that for dogs with grade 3 STSs was 148 days. Disease-free survival rates of dogs with grade 1 and 2 tumors at 1, 2, and 3 years were 88%, 75%, and 64%, respectively. One dog was treated for presumptive systemic toxicosis but recovered with medical treatment. CONCLUSIONS AND CLINICAL RELEVANCE Cisplatin-impregnated beads were generally well tolerated; good results were achieved for dogs with grade 1 or 2 STSs. Prospective, controlled studies are needed to determine efficacy of this treatment for preventing recurrence of marginally excised STSs in dogs.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma.

BACKGROUND: Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRß, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. RESULTS: mRNA for VEGFR2, PDGFRα/ß, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/ß, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/ß, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRß expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. CONCLUSIONS: Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/ß and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.

Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors.

OBJECTIVE: To determine clinical status and renal and hematopoietic function after kidney donation and identify risks associated with kidney donation in dogs. DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined prospectively at various times after nephrectomy, and pre- and postnephrectomy CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine creatinine ratio were compared. Six dogs had postnephrectomy renal volume determined ultrasonographically, and 4 of those dogs also underwent scintigraphic determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs were clinically normal at the time of reevaluation. There were no significant differences between prenephrectomy and postnephrectomy values for BUN concentration or urine specific gravity. Mean postnephrectomy serum creatinine concentration was significantly greater than prenephrectomy concentration. Mean serum phosphorus concentration was significantly decreased after nephrectomy, and mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were significantly increased after nephrectomy. Postnephrectomy renal volume was greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51 mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and hematopoietic variables were within reference ranges in dogs examined up to 2.5 years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest in dogs < 1 year of age at donation. Donor age, along with histocompatability, may be an important factor in selecting dogs for kidney donation.