ABSTRACT OF THE WEEK

Veterinary dermatology
Volume 28 | Issue 2 (April 2017)

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

Vet Dermatol. April 2017;28(2):195-e44.

Amanda L Ackermann¹, Elizabeth R May², Linda A Frank³

¹ Department of Small Animal Clinical Sciences, University of Tennessee, 2407 River Drive, Knoxville, TN, 37996, USA.; ² Department of Small Animal Clinical Sciences, University of Tennessee, 2407 River Drive, Knoxville, TN, 37996, USA.; ³ Department of Small Animal Clinical Sciences, University of Tennessee, 2407 River Drive, Knoxville, TN, 37996, USA.

Abstract

BACKGROUND:Mycophenolate mofetil (MMF) is a lymphocytotoxic immunosuppressive agent used in human and companion animal medicine for the treatment of immune-mediated disease. Mycophenolate mofetil is reported to have reduced myelotoxicity and hepatotoxicity when compared to azathioprine.

OBJECTIVES:It was hypothesized that treatment with MMF as a secondary agent with glucocorticoids would be effective in treating immune-mediated skin disease. In addition, adverse effects associated with the drug are reported.

ANIMALS:Fourteen dogs from a hospital population diagnosed with immune-mediated skin disease.

METHODS:A retrospective review of medical records from 2010 to 2015 was used to identify dogs with immune-mediated skin disease that were treated with MMF.

RESULTS:All dogs were treated with MMF (mean dose 14.7 mg/kg twice daily) in conjunction with glucocorticoids. Ten of 14 cases showed positive results, with complete remission in eight cases and partial remission in two cases. Mean time to remission was 5.7 weeks. Therapy was discontinued in one case (perianal fistula) due to lack of response. Adverse events were noted in six cases and included diarrhoea (n = 6), haematochezia (n = 2), vomiting (n = 3) and papilloma formation (n = 1). Therapy was discontinued in two cases with diarrhoea. Mycophenolate mofetil was discontinued in an additional case because of a diagnosis of neoplasia. All other adverse events were self-limiting or easily medically managed. No hepatotoxicity or bone marrow suppression was noted.

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

Companion Notes

Retrospective report on the efficacy of mycophenolate mofetil for immune-mediated skin disease in 14 dogs

Introduction on mycophenolate mofetil (MMF)

- immunosuppressant used in human and companion animal medicine

- in companion animals used for immune-mediated conditions including the following:

- hemolytic anemia

- acquired myasthenia gravis

- pemphigus vulgaris

- MMF is the prodrug of mycophenolic acid (MPA)

- MPA inhibits inosine monophosphate dehydrogenase (IMPDH)

- IMPDH is integral in formation of guanosine

- IMPDH inhibition depletes guanine nucleotides

- MPA cytotoxicity is specific towards T and B lymphocytes

- cells dependent on the de novo pathway for purine synthesis

- unlike other cell types that can use a salvage pathway

- a salvage pathway lacking in lymphocytes

- also, MPA is specific for the type II isoform of IMPDH

- the form most abundant in activated lymphocytes

- MMF acts through cytotoxicity to T and B lymphocytes

- therefore, it suppresses cell-mediated and humoral immune responses

- advantages of MMF over other adjunct immunosuppressive agents

- rapid onset of action

- available parenteral formulation

- reported lower myelotoxicity and hepatotoxicity compared to azathioprine

- in canine medicine:

- rapid oral absorption occurs with significant enterohepatic circulation

- reported adverse effects in dogs include the following:

- diarrhea

- vomiting

- weight loss

- allergic reaction

- facial swelling and ventral abdominal urticaria after IV MMF

- papillomatosis

Study design

- study population: dogs seen at University of Tennessee from 10-15

- 14 dogs with immune-mediated skin disease treated with MMF

- mycophenolate mofetil (MMF), mean dose 14.7 mg/kg bid

- MMF twice daily, 11 of the 14 cases initially

- mean initial dose was 15.0 mg/kg bid

- MMF once daily, 3 of the 14 cases initially

- 20 mg/kg, 21 mg/kg and 39 mg/kg

- in conjunction with glucocorticoids

- initially given at immunosuppressive levels

- tapered if/when remission achieved

- history & signalment

- median age: 6.5 years of age with a range of 0.9-11 years

- mean weight: 23.3 kg with a range of 5-45.7 kg

- inclusion criteria included the following:

- diagnosis of idiopathic autoimmune or immune-mediated skin disease

- pemphigus foliaceus

- vasculitis

- vesicular cutaneous lupus erythematosus (VCLE)

- perianal fistula

- subepidermal bullous disease

- baseline laboratory assessment

- at least 1 recheck

- initial/additional immunosuppressive therapies included the following:

- prednisone

- dexamethasone

- triamcinolone

- ciclosporin

- chlorambucil

- topical tacrolimus

- procedure: records retrospectively reviewed

Results

- positive results found in 10 cases

- complete remission, 8 cases

- partial remission, 2 cases

- mean time to remission: 5.7 weeks

- MMF discontinued, 2 cases

- lack of response with perianal fistula, 1

- diagnosis of neoplasia, 1

- efficacy by underlying disease

- pemphigus foliaceus

(median time to remission: 6.5 weeks with a range of 3-8 weeks)

- resolution of all lesions, 6 of 9 dogs

- partial remission, 2 cases

- remaining lesions mild and limited to the face

- discontinued due to adverse events, 1 case

- epidermolysis bullosa, full remission in the 1 dog

- vesicular cutaneous lupus erythematosus, full remission in the 1 dog

- treatment discontinued in perianal fistula, vasculitis and histiocytosis cases

- due to adverse events

- adverse events noted in 8 cases

- self-limiting or easily medically managed in 4 of the 6

- therapy discontinued in 2 of the 6 cases

- vomiting and diarrhea, 1 dog

- hematochezia, 1 dog

- diarrhea, 6

- vomiting, 3

- hematochezia, 2

- probable papilloma formation, 1

- neoplasia

“Most dogs achieving remission required concurrent glucocorticoid therapy (n = 6); however, the steroid doses were low when compared to immunosuppressive doses and were administered at a maximum frequency of every other day…”

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