This study will test the safety and effectiveness of the drug methimazole in treating
polymyositis and dermatomyositis-inflammatory muscle diseases causing weakness and muscle
wasting. Although it is not known what causes of these diseases, abnormal immune function
is thought to be involved. Recent studies indicate that methimazole, which has been used
for many years to treat thyroid disease, may alter immune activity by affecting the
interaction between white blood cells called lymphocytes and certain molecules on cell
surfaces. This study will examine the effects of methimazole on immune activity and muscle
strength in patients with inflammatory muscle diseases and evaluate the drug side effects.
Patients with polymyositis and dermatomyositis who have normal thyroid function may be
eligible for this study [age requirement?]. Candidates will undergo a history and physical
examination; blood and urine tests; chest X-ray; muscle strength testing, daily living
skills questionnaire, and speech and swallowing evaluation; magnetic resonance imaging of
muscles; and muscle biopsy (removal of a small piece of muscle tissue under local
anesthetic). When indicated, some candidates may also have cancer screening tests (for
example, mammogram, Pap smear), a lung function test to measure breathing capacity, or an
electromyogram, in which small needles are inserted into a muscle to measure the electrical
Participants will take 30 mg of methimazole by mouth twice a day for 6 months. They will
have blood tests weekly for the first 2 weeks and then every other week for the rest of the
study to measure blood counts and liver and thyroid function. Blood will also be drawn for
white blood cell studies during the screening evaluation, at the beginning of therapy, 6 to
12 weeks after therapy starts, at the end of the 6-month treatment period, and 1 and 3
months after therapy ends. Muscle enzyme and urine tests will be done once a month..
During drug treatment, patients will have periodic physical examinations and blood and
muscle function tests to evaluate the response to therapy.
This open label pilot study will assess the (1) activity of methimazole (MMI), a
down-regulator of MHC Class I transcription used in treatment of autoimmune thyroiditis
(AIT), on the tissue expression of HLA class I and its (2) efficacy as measured by serum
muscle enzyme levels and manual muscle testing in up to twenty patients with dermatomyositis
(DM) or polymyositis (PM). Participants will have persistent weakness, laboratory evidence
of inflammation and be on a stable regimen of medication to control their myopathy. MMI
will be administered orally at 30 mg twice a day for six months. Patients will be evaluated
for alteration of HLA Class I expression in muscle and peripheral blood lymphocytes (PBL)
and drug-related toxicities during the study and for three months after the discontinuation
Diagnosis of Polymyositis or Dermatomyositis.
Baseline muscle weakness score of less than or equal to 139 out of 160 on manual testing
Baseline functional assessment score of less than or equal to 82 out of 91.
Ability to provide informed consent to all aspects of the study after full information is
Age equal to or older than 18.
A diagnosis of classic or definite polymyositis or dermatomyositis (Critieria A and B plus
at least one of the three other criteria):
1. Symmetrical proximal muscle weakness;
2. Muscle biopsy abnormalities at some time during their disease:
i. degeneration and regeneration of muscle fibers
iv. interstitial mononuclear infiltration;
c. Elevation of serum creatinine phosphokinase (CPK), transaminases, lactic dehydrogenase
(LDH) or aldolase activity;
d. Electromyography (EMG) triad of changes
i. small amplitude, short duration polyphasic motor unit potentials
ii. fibrillations, positive sharp waves, increased insertional irritability
iii. spontaneous bizarre high frequency discharges;
e. Typical skin rash of DM.
Willingness to undergo 2 muscle biopsies.
Evidence of active disease as measured by weakness, and an elevated CK or an active MRI.
Must be tapered to a stable dose of steroid equal to or less than 0.50 mg/kg/day
equivalent of prednisone for one month prior to the study.
If on additional immunosuppressive drugs, the drugs must be maintained at a stable dose
for 1 month prior to the initiation of therapy and will be maintained throughout the
Women of childbearing potential and men whose partners are of childbearing potential must
practice an acceptable form of contraception. No pregnant females or nursing mothers.
No history of hepatitis or abnormal liver function tests.
No history of prior thyroid disease.
No active acute or chronic infections requiring antimicrobial therapy, or serious viral or
No preexisting or coexisting malignancy other than basal cell and localized squamous cell
carcinoma of the skin.
No history of cerebrovascular accidents, seizure disorder, aseptic meningitis, transverse
myelitis or central nervous system disease.
No history of documented coronary artery disease, cardiomyopathy, greater than
first-degree heart block, or dysrhythmia requiring therapy.
No confounding medical illness that in the judgement of the investigators would pose added
risk for study participants.
No anemia requiring maintenance blood transfusions; leukoplakia with WBC less than 3,000
micrograms or absolute neutrophil count less than 2,000 micrograms; and platelet count
less than 100,000 micrograms on at least two different occasions.
No history of (or current) autoimmune hemolytic anemia.
No current anticoagulant therapy.