Case Series

Use of mycophenolate mofetil as a rescue agent in

the treatment of severe generalized myasthenia
gravis in three dogs
Amanda L. Abelson, DVM; G. Diane Shelton, DVM, PhD; Megan F. Whelan, DVM, DACVECC;
Lilian Cornejo, DVM, DACVIM; Scott Shaw, DVM, DACVECC and Therese E. OToole, DVM,
DACVIM
Abstract
Objective To describe the use of IVand oral mycophenolate mofetil (MMF) as adjunctive therapy in 3 dogs
with severe generalized myasthenia gravis.
Case Series Summary Three dogs suffering from severe generalized myasthenia gravis as conrmed by
acetylcholine antibody titers were treated with MMF as part of their treatment regimens. All 3 dogs had
radiographic evidence of megaesophagus and suffered from severe regurgitation. Each dog was initially
treated with pyridostigmine and supportive agents. When clinical remission was not achieved, IV MMF was
administered to all dogs. Signs of clinical remission were apparent within 48 hours and all dogs were later
maintained on oral MMF following resolution of regurgitation.
New or Unique Information Provided This is the rst report of the use of IV MMF as adjunctive treatment
in dogs with severe generalized myasthenia gravis. Outcome was favorable in all 3 dogs and no adverse
effects were noted from the MMF.
(J Vet Emerg Crit Care 2009; 19(4): 369374) doi: 10.1111/j.1476-4431.2009.00433.x
Keywords: acetylcholine receptor antibody, immunosuppressive agents, megaesophagus, neuromuscular
disease, purine analog
Introduction
Acquired myasthenia gravis (MG) is an immune-
mediated neuromuscular disorder causing muscle
weakness and fatigue resulting from autoantibody-me-
diated destruction of acetylcholine receptors (AChRs)
on the postsynaptic membrane of the neuromuscular
junction.
Clinical signs of MG can be classied into 4 major
groups, those with only focal clinical signs in the
absence of generalized weakness, mild cases with a
progressive generalized weakness in the absence of
megaesophagus, those with a more severe form of acute
generalized weakness and megaesophagus, or as a para-
neoplastic syndrome associated with thymoma.
14
Focal
clinical signs including weakness of the facial, laryn-
geal, esophageal, or pharyngeal muscles in the absence
of generalized weakness occur in up to 43% of dogs
with MG.
5
Generalized forms can be mild without
megaesophagus or rapidly progress to recumbency and
respiratory distress in acute fulminating MG.
6
Gener-
alized forms are distinguished from each other by the
presence or absence of megaesophagus, the rate at
which weakness progresses and the presence or ab-
sence of thymoma. Megaesophagus occurs in up to 90%
of the cases of generalized MG.
5
Aspiration pneumonia
resulting from persistent regurgitation can further ex-
acerbate weakness. In these severe cases, intensive
management, sometimes including assisted mechanical
ventilation, is required to provide adequate support
until treatment can achieve an improvement in strength
and clinical remission.
7
Because the cost of this inten-
This work was conducted in entirety at the Cummings School of Veterinary
Medicine at Tufts University.
This study was not supported by any funding agency.
Address correspondence and reprint requests to
Dr. Therese E. OToole, Department of Clinical Sciences, Cummings School
of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton,
MA 01356, USA.
Email: theresa.otoole@tufts.edu
From the Department of Clinical Sciences, Cummings School of Veterinary
Medicine, Tufts University, North Grafton, MA 01356 (Abelson, Cornejo,
Shaw, OToole); Department of Pathology, University of California, San
Diego, La Jolla, CA 9037 (Shelton); Department of Emergency and Critical
Care, Angell Animal Medical Center, Boston, MA 02130 (Whelan).
Journal of Veterinary Emergency and Critical Care 19(4) 2009, pp 369374
doi:10.1111/j.1476-4431.2009.00433.x
& Veterinary Emergency and Critical Care Society 2009 369
sive management can be prohibitive to many owners,
the availability of effective, efcient, and affordable
treatment protocols are essential. Additionally, the
prognosis for survival to discharge for this population
of severely affected dogs is guarded to poor, despite
hospitalization and critical care management.
2,6
The presence of autoantibodies against muscle AChRs
is diagnostic of MG.
8
Anticholinesterase (AChE) drugs
inhibit the enzymatic hydrolysis of acetylcholine allow-
ing for its prolonged interaction with available AChRs.
The effectiveness of these agents, however, relies on the
availability of AChRs, which are reduced in MG by the
binding of autoantibodies and subsequent receptor loss
on the postsynaptic membrane. Although MG is an auto-
immune disease, the natural course of the disease is for
spontaneous remission in the absence of immunosup-
pression.
9
However, in severe cases of MG that do not
respond to AChE treatment alone, immunosuppressive
agents should be considered.
Although there are no controlled clinical studies that
compare their usage, immunosuppressive agents includ-
ing corticosteroids, azathioprine (AZA), and cyclosporine
have all been used in the treatment of canine MG.
2,10,11
Prednisone, however, has been associated with increased
muscle weakness and can exacerbate clinical signs, and
AZA and cyclosporine may require several days of ad-
ministration to reach effective blood levels.
10,12,13
To pro-
vide successful rescue from severe generalized or acute
fulminating MG, or MG that has failed to adequately
respond to conventional treatments, a drug must provide
an immediate effect, be relatively free of complications,
and be available for veterinary use. A parenteral formu-
lation would be advantageous for patients with severe
regurgitation. Human intravenous immunoglobulin
(hIVIG) and plasmapheresis are used in human patients
for therapy of fulminant MG, but these treatments have
either limited availability or are cost-prohibitive in vet-
erinary patients.
14,15
Mycophenolate mofetil (MMF) inhibits nucleic acid
synthesis in T- and B-cells and was introduced for use in
human renal transplant patients about 25 years ago. Now
widely used to prevent allograft renal transplant rejec-
tion,
16
MMF is also used to prevent allograft rejection in
other transplant patient populations. MMF has recently
been used in the treatment of human immune-mediated
diseases, including MG, systemic lupus erythematosus,
Crohns disease, immune-mediated hemolytic anemia
(IMHA), and immune-mediated thrombocytopenia.
17
MMF has been described in the treatment of canine
aplastic anemia, IMHA, and oral MMF has been reported
for use in canines with MG.
1821
In this report we de-
scribe the use of both parenteral and oral MMF in 3 dogs
with severe generalized MG that presented to the emer-
gency service at a veterinary teaching hospital.
Case 1
An 8-year-old spayed female Labrador Retriever was
referred for evaluation following 4 days of regurgita-
tion and progressive generalized weakness. A dilated
esophagus and a soft tissue opacity in the cranial me-
diastinum were apparent on thoracic radiographs. Ab-
normalities on CBC and serum chemistry included
mild monocytosis (1.75 10
9
/L; reference interval,
0.11.5 10
9
/L), slight hypercalcemia (2.92 mmol/L
[11.7 mg/dL]; reference interval, 2.352.90 mmol/L
[9.411.6 mg/dL]), increased aspartate aminotrans-
ferase (169 U/L; reference interval, 1654 U/L), and
increased creatine kinase (637 U/L; reference interval,
48400 U/L). Total thyroxine, free thyroxine, and thy-
roid stimulating hormone were all normal. Pyridostig-
mine
a
(1.4 mg/kg, PO, q 12 h) was started shortly after
admission. Other treatments included famotidine
b
(0.5 mg/kg, IV, q 12 h), and IV uids (lactated Ringers
solution
c
[LRS], 90 mL/kg/d). Thoracic computed
tomographic examination conrmed a cranial media-
stinal mass. Serum AChR antibody titer
d
was increased
(6.55 nmol/L; reference limits, o0.6 nmol/L). With
minimal improvement, a single dose of hIVIG
e
(0.5
g/kg, IV, over 6 h) was administered. The dog im-
proved over the following 48 hours and was walking. A
presumed aspiration event, however, prompted emer-
gent intubation and assisted ventilation. The precipi-
tating cause of the event was not entirely determined,
but suspected airway obstruction due to aspiration of
stomach contents (kibble) was considered likely. Extu-
bation was accomplished the following day, and
imipenem
f
(6 mg/kg, IV, q 8 h) was added for hospi-
tal-acquired aspiration pneumonia. Improved, the dog
underwent a median sternotomy the following week.
The cranial mediastinal mass was removed in its en-
tirety, and thymoma with complete resection was con-
rmed on histopathology. Recovery from surgery was
uneventful but by the fth postoperative day regurgi-
tation and weakness returned. In addition to
pyridostigmine (1.5 mg/kg, PO, q 8 h) a second infu-
sion of hIVIG was administered. Within 4 days the
dogs weakness and regurgitation again resolved. On
the 24th day of hospitalization the dog was nally dis-
charged on pyridostigmine (1.5 mg/kg, PO, q 12 h). A
postoperative AChR antibody titer was 4.02 nmol/L.
The dog initially did well but returned to the hospital
12 days following discharge for relapse of muscle
weakness. A third infusion of hIVIG was given but this
time the dog developed erythema and anxiety, prompt-
ing discontinuation before its completion. The dog,
however, responded again, was stronger, and was dis-
charged with the addition of AZA
g
(2 mg/kg, PO, q
24 h). Although strong on discharge the dog returned
& Veterinary Emergency and Critical Care Society 2009, doi: 10.1111/j.1476-4431.2009.00433.x 370
A.L. Abelson et al.
again 5 days following this for rapidly progressive
weakness and regurgitation. Pyridostigmine (0.02 mg/
kg/h, IV) was reinstituted and a fourth infusion of hI-
VIG was attempted due to the rapid deterioration in
muscle strength and fear of an aspiration event. Within
minutes of starting the hIVIG the dog developed re-
spiratory distress, tachycardia, and diffuse erythema.
The hIVIG was discontinued, and the dog was treated
for anaphylaxis. Over the next 2 days, the dog required
intubation and continuous monitoring by a dedicated
clinician or technician. Multiple attempts to extubate
the dog were unsuccessful, and the dog suffered several
respiratory arrests. An infusion of methylprednisolone
sodium succinate
h
(20 mg/kg, over 30 min) was ad-
ministered, but the dog did not respond and weakness
was so profound that the dog could not blink, move its
head, or negotiate the tongue to clear the mouth. The
oral cavity and esophagus required repeated suction-
ing, and if extubated the dog would aspirate into the
trachea requiring emergent suctioning. With failure to
respond to IV pyridostigmine or glucocorticoids, and
the analphylactic reaction to hIVIG, an infusion of
MMF
i
was prepared (15 mg/kg, diluted in 500 mL of
0.45% saline and 2.5% dextrose) and given over 4 hours.
The dog improved within 24 hours and a second MMF
infusion was given the following day. With decreased
salivation and regurgitation, the dog was then able to
receive MMF orally (11 mg/kg, PO, q 12 h). With con-
tinued improvement, the dog was discharged 1 week
later on pyridostigmine (1.5 mg/kg, PO, q 12 h) and
continuation of MMF. Pyridostigmine was discontin-
ued 1 week later due to gastrointestinal upset and the
dog was maintained on MMF with a gradual decrease
in the dose (7 mg/kg, PO, q 12 h). One year later
the dog was reported to be doing well. AChR antibody
titers at this time were 1.58 nmol/L, demonstrating
that while the dog is clinically normal, she is not in
remission.
Case 2
A 7-year-old castrated male Golden Retriever was
referred for 1 week of regurgitation and generalized
weakness. Neurological examination revealed de-
creased withdrawal reexes and generalized weakness.
The dog was hypersalivating and was mildly tachy-
pneic at 50/min. The remainder of the physical exam-
ination was within normal limits. CBC and serum
chemistry abnormalities included slightly decreased
platelets (159 10
9
/L; reference interval, 181
525 10
9
/L), mild hypernatremia (162 mmol/L; refer-
ence interval, 142158 mmol/L), increased serum
aspartate aminotransferase (168 U/L), and increased
serum creatine kinase (1166 U/L). A gas distended
esophagus was apparent on thoracic radiographs. A
positive response to edrophonium chloride
j
(0.1 mg/kg,
IV) provided a presumptive diagnosis of MG. Pyrid-
ostigmine in a constant rate infusion (CRI) was started
at 0.01 mg/kg/h and was gradually increased to
0.025 mg/kg/h. Other treatments included metoclo-
pramide
k
CRI (1 mg/kg/d, IV), dolasetron
l
(1 mg/kg,
IV, q 24 h), and IV uids (LRS at 60 mL/kg/d). En-
rooxacin
m
(10 mg/kg, IV, q 24 h) and clindamycin
n
(10 mg/kg, IV, q 12 h) were also started because of con-
cerns that early aspiration pneumonia was present.
Thoracic computed tomographic and abdominal ultra-
sonographic examinations identied no underlying
masses. Serum-free thyroxine and thyroid stimulating
hormone were normal. A serum AChR antibody titer
was elevated (10.77 nmol/L). By day 3 of hospitaliza-
tion the dog had less regurgitation, allowing the
pyridostigmine to be given orally (1 mg/kg, PO,
q 8 h); however, the dog showed little improvement in
ability to stand or ambulate. A CRI of MMF was given
(16 mg/kg, over 2 h). Within 24 hours strength was
markedly improved, the dog was walking without ab-
normality, and there was no regurgitation. MMF
(10 mg/kg, PO, q 12 h) was continued and the dog
was discharged after 1 week of hospitalization on MMF,
pyridostigmine (1 mg/kg, PO, q 8 h), and enrooxacin
(9 mg/kg, PO, q 12 h). Follow-up AChR antibody titer 9
months after discharge was 0.41 nmol/L and the dog
was asymptomatic for MG. Following this, the owners
administered MMF sporadically (estimated 10 mg/kg,
every third day), and after 3 months of this dosing the
AChR antibody titer was 0.59 nmol/L.
Case 3
A 9-year-old castrated male Golden Retriever was re-
ferred for 2 weeks of regurgitation. The dog had pelvic
limb weakness but was ambulatory. Referring CBC and
serum chemistry prole were unremarkable. Mega-
esophagus and an alveolar pattern consistent with
aspiration pneumonia were apparent on thoracic ra-
diographs. A strongly positive response was observed
when given edrophonium chloride. The dog was
started on neostigmine
o
(0.04 mg/kg, IM, q 6 h). Cyto-
logic evaluation of a transtracheal wash conrmed sep-
tic inammation consistent with pneumonia, which
was treated with ampicillin
p
(22 mg/kg, IV, q 8 h) and
enrooxacin (10 mg/kg, IV, q 24 h). Other therapy in-
cluded famotidine (0.5 mg/kg, IV, q 12 h), IV uids
(LRS at 90 mL/kg/d), and suctioning of the esophagus
via an indwelling nasoesophageal tube.
q
Free thyroxine
and thyroid stimulating hormone assays and an adre-
nocorticotropin stimulation test were normal. An AChR
antibody titer was 1.9 nmol/L. Because of ileus 3 days
& Veterinary Emergency and Critical Care Society 2009, doi: 10.1111/j.1476-4431.2009.00433.x 371
Mycophenolate mofetil in myasthenia gravis
later, neostigmine was discontinued and pyridostig-
mine CRI (0.01 mg/kg/h) was started and then later
increased (0.02 mg/kg/h). An infusion of hIVIG (0.5 g/
kg, over 6 h) was given due to continued weakness. The
dog gradually improved over the following week.
Pyridostigmine was given orally (1.3 mg/kg, PO,
q 8 h), and the dog was discharged on day 13 of hos-
pitalization on continuation of pyridostigmine and an-
tibiotics. With radiographic evidence of resolving
pneumonia 3 weeks later, AZA (2.5 mg/kg, PO,
q 24 h) was started, but the following day the dog
was readmitted to the hospital for recurrent weakness,
hypersalivation, and regurgitation. Pyridostigmine CRI
was restarted and oral medications were discontinued.
A preparation of MMF (20 mg/kg, diluted in 500 mL of
0.45% saline and 2.5% dextrose) was infused over 4
hours once daily for 3 consecutive days, and then con-
tinued orally (10 mg/kg, q 12 h) starting on the fourth
day when the dog demonstrated improvement in
strength and regurgitation, along with oral pyridostig-
mine the following day. The dog was discharged the
next day with oral pyridostigmine, MMF, and AZA.
Serial follow-up AChR antibody titers over the 6
months following discharge trended toward normal,
and the AZA was tapered and discontinued. Two
months later an AChR titer was 0.49 nmol/L. At that
time MMF therapy was incrementally decreased (from
10 to 3.2 mg/kg, q 12 h). When the titer increased to
0.59 nmol/L following the dose reduction, the MMF
dose was increased (6.5 mg/kg, PO, q 12 h).
Discussion
MMF is a synthesized prodrug of mycophenolic acid
(MPA), a compound rst discovered in 1893 when it
was isolated as a fermentation product from Penicillium
brevicompactum. In 1990, MPA was esteried to a
morpholinoethyl group creating MMF.
22
Actions of
MMF include reduction of the proliferation of lympho-
cytes, down-regulation of the expression of cell surface
adhesion molecules, and a decrease in antibody pro-
duction.
21
Specifically, MMF inhibits inosine-5
0
-mono-
phosphate dehydrogenase (IMPDH), an enzyme that
limits the rate of de novo guanosine nucleotide synthe-
sis. The lack of guanosine nucleotide impairs the ability
of the cell to synthesize nuclear genetic material and
halts transcription and translation within the cell. Two
isoforms of IMPDH (types I and II) have been identied
with MMF having a 5 times greater afnity for the type
II isoform. The type II isoform is expressed in activated
T- and B-cell lymphocytes, whereas the type I isoform is
expressed in most cell types.
23
Specicity for T- and B-cells makes MMF an attrac-
tive therapy for autoimmune diseases. Studies in hu-
mans investigating the efcacy of MMF in MG have
been inconclusive. Preliminary, small scale studies
showed promise with the addition of MMF for poorly
controlled MG.
24,25
Despite a positive response in 73%
of cases reported in a retrospective study of 85 human
patients with MG,
26
2 recent large, multicenter, double-
blinded, prospective studies put into question the ef-
cacy of MMF in the treatment of mild to moderate
MG.
27,28
These studies compared the use of prednisone
as a sole agent versus prednisone and MMF in
the treatment of myasthenics with mild to moderate
disease, and demonstrated that MMF provided no ben-
et over the use of prednisone alone during an initial
12-week period of therapy. However, the studies ex-
cluded patients in which MMF therapy may be most
benecial, those with severe weakness that may be ex-
acerbated by prednisone, and in patients where other
treatment modalities had failed. Large, multicenter
studies in these populations are still indicated.
The wide range in degree of both severity of clinical
signs and response to therapy can make the treatment
of canine MG difcult. One study indicated that in the
absence of thymoma, many dogs suffering from MG
will go into spontaneous remission and simply require
treatment with AChEs until the disease has taken its
clinical course.
9
Other studies demonstrate that up to
60% of canine myasthenics will be euthanized within 1
year of diagnosis, usually as a result of aspiration
pneumonia.
2
These studies, however, cannot be directly
compared as high dosages of prednisone were given in
the second study, which has subsequently been shown
to exacerbate muscle weakness.
To date no prospective, randomized trial proving ef-
cacy of any 1 or combination of treatment regimens for
MG in dogs has been performed. Various therapies
have been anecdotally reported and advocated in the
veterinary literature including AZA, cyclosporine,
MMF, and prednisone.
1012,19
While prednisone is the mainstay of therapy for hu-
man myasthenics, it may not be the best treatment for
canine myasthenics. Aspiration pneumonia is a com-
mon sequela to generalized MG in the dog but not in
humans due to the fact that the canine esophagus is
composed of entirely striated muscle, whereas in the
human, only the proximal 26 cm of the esophagus is
striated muscle with the remainder being smooth mus-
cle.
29
Because of the aspiration pneumonia, dogs are
more likely to suffer respiratory fatigue from a combi-
nation of diseased lung as well as weakened respiratory
muscles. Prednisone therapy may cause further muscle
weakness and lead to respiratory distress.
Cyclosporine and AZA have been advocated as im-
munosuppressive therapies for canine MG. However,
reports indicate that they can take several days to
& Veterinary Emergency and Critical Care Society 2009, doi: 10.1111/j.1476-4431.2009.00433.x 372
A.L. Abelson et al.
months to take effect.
9,11
hIVIG is reported in human
myasthenics to have a rapid onset of action and has
been reported for use in dogs with other immune-
mediated diseases including IMHA, immune-mediated
thrombocytopenia, and pemphigus foliaceous.
3033
Its
use has not been previously reported in canine my-
asthenics. Two dogs in this report received hIVIG. Al-
though both dogs appeared to respond initially to
hIVIG, clinical signs recurred in both, and, if remission
had been achieved with hIVIG it was not lasting. Fur-
thermore, efcacy of hIVIG in dogs with MG has not
been proven in a clinical trial and, as evidenced by the
reaction the dog in the rst case demonstrated upon
receiving subsequent infusions, the use of repeated
dosing of hIVIG in dogs may be risky, limiting it to a
single dose.
MMF is formulated for both IV and oral dosing,
allowing it to be administered both in the acute setting
and for long-term therapy. The 3 cases reported here
suggest that MMF may have benet as an adjunctive
agent in poorly controlled MG or as a rescue agent in
severe generalized MG when AChEs fail to improve
clinical signs. While the time frame from the start of
therapy to the onset of clinical improvement is not
known, it has been shown that following oral admin-
istration, maximal inhibition of IMPDH occurs approx-
imately 24 hours after dosing suggesting that it has a
rapid onset of action.
34
Reported adverse effects of MMF in humans include
gastrointestinal upset, increased susceptibility to infec-
tion, teratogenic effects, increased risk of lymphoma,
allergic reaction, headache, and neutropenia that occurs
most often between days 31 and 180 following start of
therapy.
35
In canine patients the most common adverse
effects reported include weight loss, gastrointestinal
upset, and mild allergic reactions during parenteral
administration.
36,37
No adverse effects were noted in
the cases reported here. Cases 1 and 3 had serial CBCs
performed during the rst year of therapy and no ab-
normalities were detected. Case 2 did not have a fol-
low-up CBC. The lack of allergic reaction in these cases
may be due to the fact that 2 dogs were receiving con-
current immunosuppressive agents at the time of infu-
sion. Gastrointestinal upset has been reported to occur
primarily in doses equal to or 30 mg/kg.
36
The dose of MMF for dogs with MG has not been
established. One study investigating the IV and oral
pharmacokinetics of MMF in healthy dogs suggests
that a higher dose, and a more frequent dosing sched-
ule than used in this case series would be required. The
study found that oral MMF at roughly 20 mg/kg pro-
duced low plasma levels and a relatively short half-life
of only 45 minutes.
35
However, this study did not ex-
amine the biologic effects of MMF, and it may be that
the effects outlast detectable plasma levels. A second
study investigating oral doses (1030 mg/kg, twice
daily) of MMF in dogs following stem cell transplan-
tation found that there was no linear relationship be-
tween dose of MMF and MPA blood levels. In addition,
there was wide interpatient variability of MPA blood
levels. The authors hypothesized that this was due to
differences in enterohepatic recirculation between dogs.
The authors suggested that MMF may need to be dosed
more frequently and that dogs with intestinal impair-
ment or receiving medications that impede enterohe-
patic recirculation may require higher doses.
36
MMF is available in 250 and 500 mg capsules as well
as 500 mg vials, and is infused over a period of not o2
hours. To the authors knowledge, this is the rst report
of dogs suffering from severe generalized MG treated
with IV MMF as a rescue agent. The dosages admin-
istered to dogs in this report were extrapolated from an
oral dose reported by Dewey et al
19
(520 mg/kg, PO,
q 12 h). The dogs received differing IV doses because
each received the entire reconstituted 500 mg vial.
Based on these clinical results, it seems reasonable to
advocate the use of MMF as a rescue agent for canine
patients with severe generalized MG that is refractory
to other treatment regimens. A prospective, random-
ized-clinical trial is indicated to more denitively es-
tablish the benet of MMF in MG treatment protocols.
Footnotes
a
Mestonin, Sandoz, Broomeld, CO.
b
Famotidine Injection, Baxter Healthcare Corp, Deereld, IL.
c
Lactated Ringers solution, Baxter Healthcare Corp.
d
Comparative Neuromuscular Laboratory, Department of Pathology,
University of California, San Diego, CA.
e
Gammagard, Baxter Healthcare Corp.
f
Primaxin IV, Merck and Co Inc, Whitehouse Station, NJ.
g
Azathioprine Tablet, Roxane Laboratories Inc, Columbus, OH.
h
Solu Medrol, Pzer Inc, New York, NY.
i
Cellcept, Roche Laboratories Inc, Nutley, NJ.
j
Enlon, Baxter Healthcare Corp.
k
Reglan Injection, Baxter Healthcare Corp.
l
Anzemet, Aventis Pharmaceuticals Inc, Kansas City, MO.
m
Baytril Injection, Bayer Healthcare LLC, Shawnee Mission, KS.
n
Clindamycin Injection, Hospira Inc, Lake Forest, IL.
o
Neostigmine Methylsulfate Injection, Baxter Healthcare Corp.
p
Ampicillin Injection, Abraxis, Schaumburg, IL.
q
Kendall Argyle Feeding Tube, Tyco Health Care Group, Manseld, MA.
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