Use of mycophenolate mofetil to treat immune‐mediated skin disease in 14 dogs – a retrospective evaluation

Ackermann, Amanda L.; May, Elizabeth; Frank, Linda A.

doi:10.1111/vde.12400

Cited by 29 publications

(71 citation statements)

References 18 publications

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“…Recommended starting dosages for mycophenolate mofetil in dogs have varied from 10 to 20 mg/kg PO q12h, but gastrointestinal signs at the higher end of the dosage range often will necessitate dose reductions. Reported prevalence of diarrhea can be ≥20%, and may be delayed for 1‐2 weeks after starting treatment . Generally, starting dosages of 7‐10 mg/kg PO q12h (14‐20 mg/kg total daily dose) are associated with a much lower prevalence of diarrhea .…”

Section: Results and Recommendationsmentioning

confidence: 99%

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Swann

Garden

Fellman

et al. 2019

Veterinary Internal Medicne

187

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Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases.

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Section: Results and Recommendationsmentioning

confidence: 99%

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Swann

Garden

Fellman

et al. 2019

Veterinary Internal Medicne

187

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“…In cats and dogs, the disposition of MPA seems to be highly variable (Ackermann et al., ; Slovak, Rivera, et al., ), as reported in humans (Le Meur et al., ; Zabotti et al., ; Mok, ). Variability in drug disposition of MPA could result in unpredictable safety and efficacy and explain interindividual variability in drug tolerance (Streicher et al., ; Martial et al., ; Filler, Alvarez‐Elías, McIntyre, & Medeiros, ; Zhang & Chow, ).…”

Section: Introductionmentioning

confidence: 94%

“…The prodrug mycophenolate mofetil (MMF) has been shown to be a promising drug for the treatment of autoimmune diseases in dogs and cats (Ackermann, May, & Frank, 2017;Bacek & Macintire, 2011;Machka et al, 2014;Segev, Cowgill, Heiene, Labato, & Polzin, 2013;Yau & Bianco, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Following administration, MMF is converted rapidly into the active metabolite mycophenolic acid (MPA; Lange et al, 2008;Slovak, Rivera, Hwang, Court, & Villarino, 2017). In dogs and cats, MPA is biotransformed into stable and nonstable metabolites by liver microsomal enzymes (Ackermann et al, 2017;Slovak, Mealey, & Court, 2017). Immunosuppressive doses of MMF can cause gastrointestinal adverse effects in some dogs and cats (Neerman & Boothe, 2003;Lange et al, 2008;Ackermann et al, 2017;Slovak, Mealey, et al, 2017), suggesting that MPA may show a relatively narrow therapeutic index in these species.…”

Section: Introductionmentioning

confidence: 99%

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Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone

Morassi

Vélez

Slovak

et al. 2018

Vet Pharm & Therapeutics

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Mycophenolic acid (MPA) has been shown to be promising for the treatment of autoimmune diseases in dogs and cats. In humans, MPA is highly bound to plasma proteins (~97%). It has been recommended to monitor free drug plasma concentrations because the free MPA correlates with its immunosuppressive effect. However, it is unknown if MPA is highly bound to plasma proteins in dogs and cats. The objectives of this study were to determine the extent of plasma protein binding of MPA and evaluate the effect of prednisolone and dexamethasone on the extent of protein binding of MPA in dogs and cats. The extent of plasma protein binding of MPA was determined in plasma collected from clinically healthy adult cats (n = 13) and dogs (n = 14) by combining high-throughput dialysis and ultra-high-liquid chromatography. This study reveals that MPA is highly bound to plasma proteins (>90%) in dogs and cats, mean extent of binding of MPA at 15 μg/ml to plasma proteins being 96% (range, 95%-97%) and 92% (range, 90%-93%) for dogs and cats, respectively. In dog plasma, MPA is primarily bound to albumin. In vitro, prednisolone increased the unbound MPA in dogs (p < .01) but not in cats (p = .07) while dexamethasone had no effect on MPA plasma binding in either species (p > .05). Results of this study provide valuable information for designing future pharmacokinetic and pharmacodynamic studies and also therapeutic monitoring programs for dogs and cats.

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“…Mycophenolate mofetil is the prodrug of mycophenolic acid (MPA); MPA is a potent and reversible inhibitor of de novo purine biosynthesis required for T and B lymphocyte proliferation . A retrospective study reported successful usage of oral MMP in several immune‐mediated skin diseases in dogs; the primary adverse effects involved gastrointestinal signs, diarrhoea and vomiting . Diarrhoea was observed in our case at the initial high MMF dosage and resolved by halving the daily MMF dose.…”

Section: Discussionmentioning

confidence: 78%

Treatment of exfoliative cutaneous lupus erythematosus in a German shorthaired pointer dog with mycophenolate mofetil

Ferrigno

Hoover

Blubaugh

et al. 2019

Veterinary Dermatology

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Background Immune‐modulating drugs show limited therapeutic efficacy in canine exfoliative cutaneous lupus erythematosus (ECLE); over half of ECLE dogs are eventually euthanized for their lack of response to therapy. Objective To describe a case of generalized ECLE in a dog in which mycophenolate mofetil (MMF) treatment achieved complete remission. Animal A 3‐year‐old, male castrated German shorthaired pointer was presented with a three months history of generalized scaling, erythematous macules and plaques, follicular casts and hypotrichosis affecting the head, trunk, ventrum and medial aspects of all limbs. The dog exhibited lameness and stiff gait. Methods and materials Complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and RT‐qPCR of skin biopsies. Results Histologically, skin biopsy specimens revealed lymphocyte‐rich interface dermatitis, infundibular interface mural folliculitis and periglandular lymphocytic infiltrate. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment of ECLE was initiated with oral MMF (22 mg/kg, twice daily). Within three weeks of starting MMF therapy, a marked improvement in lameness and a moderate decrease in erythema and scaling was observed. After four months, erythema, scaling and follicular casts had completely resolved, and at the time of writing the dog's ECLE remains in complete remission with twice daily MMF (10 mg/kg). The lesional skin transcriptome revealed predominant T helper 1 (Th1) lymphocytic inflammatory response with strong upregulation of interferon pathway. Conclusions and clinical importance To the best of the authors’ knowledge, this is the first reported case of successful treatment of ECLE with MMF as a single‐agent therapy.

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Use of mycophenolate mofetil to treat immune‐mediated skin disease in 14 dogs – a retrospective evaluation

Abstract: This study supports the use of MMF as a second-line immunotherapeutic in immune-mediated skin disease in dogs.

Cited by 29 publications

References 18 publications

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Ex vivo binding of the immunosuppressant mycophenolic acid to dog and cat plasma proteins and the effect of co‐incubated dexamethasone and prednisolone

Treatment of exfoliative cutaneous lupus erythematosus in a German shorthaired pointer dog with mycophenolate mofetil

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