INCLUSION CRITERIA:
Adults with a definite or probable diagnosis of PM or DM and pediatric patients five years of age and over with definite or probable JDM.
A diagnosis of JDM based on an age of onset less than 18 years of age.
Refractory myositis as defined by the intolerance to or an inadequate response to corticosteroids plus an adequate regime of at least one other IS agent.
Baseline manual muscle testing which is based on a maximum MMT-8 score of 150: Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures. Subjects with a diagnosis of JDM must meet either of the following criteria: 1) An MMT-8 score that is no greater than 125/150 in conjunction with 2 other abnormal core set measure OR 2) If MMT score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures.
If an IS agent was discontinued prior to the screening visit then there must be a:
-4 week washout for methotrexate
-8 week washout for any other IS agent
If on prednisone, the dose must be stable for 4 weeks prior to the screening visit (recommended less than or equal to 1.0 mg/kg/day).
Background therapy with at least 1 non-corticosteroid immunosuppressive agent is required at a stable dose for at lest 6 weeks prior to the screening visit (exceptions listed in the protocol).
If on plaquenil the dose should be stable for 8 weeks prior to Visit 1.
If on statin agents the dose should be stable for 8 weeks prior to Visit 1.
Ability of patient or parent to complete self-report questionnaires.
Pediatric patients must be at least 5 years of age.
Absolute neutrophil count greater than or equal to 1000/mm3; platelets greater than or equal to 100,000/mm3; hemoglobin greater than or equal to10 gm/dl.
Men and women of reproductive potential must agree to use a reliable method of birth control during the 45 week duration of the trial described in the reproductive risks section of this protocol.
Children ages 12-17 or younger children who are developmentally able to sign his/her name must give assent.
Patients must agree to forgo immunization with a live vaccine during the course of the study.
Patients must have not consumed any creatinine-containing products in the form of dietary supplements 30 days prior to the screening visit and agree not to consume any creatine products in the form of dietary supplements through the study duration.
EXCLUSION CRITERIA:
Drug-induced myositis.
Juvenile polymyositis; inclusion body myositis; cancer-associated myositis.
Myositis in overlap with another connective tissue disease (CTD) that precludes the accurate assessment of treatment response.
History of receiving a live vaccine 4 weeks prior to initiation of study treatment.
Joint disease or other musculoskeletal condition, which precludes the ability to quantitate muscle strength.
Known hypersensitivity to murine proteins.
Concomitant illness that would prevent adequate patient assessment or in the investigator's opinion pose an added risk for study participants. The clinical site investigator should consider further evaluation or consultation if clinically indicated prior to study enrollment.
-recurrent or chronic infections, including HIV, hepatitis B and C
-known liver disease (i.e. cirrhosis or other conditions compromising the synthetic function of the liver)
-disorders that would preclude accurate assessment of neuromuscular function
-cardiomyopathy or arrhythmias that in the investigators opinion poses an additional risk for study participants
-New York Heart Association Classification III or IV for congestive heart failure
-psychiatric illness that precludes compliance or neuromuscular assessment
-serum creatinine greater than 2.0mg/dl
-immunoglobulin levels at baseline that are as follows: Adults IgG or IgM values at baseline are below the LLN and Pediatric IgG or IgM values at baseline are below the LLN (pediatric age adjusted normal ranges will be followed)
Pregnant females or nursing mothers
Life threatening non-myositis illness that would interfere with the patient's ability to complete the study.
Known or suspected history of drug or alcohol abuse within the past 6 months as determined by the medical record or patient interview.
Anticipated poor compliance.
Participation in another clinical experimental therapeutic study within 30 days of screening visit.
Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator unsuitable for the study.
Any history of receiving rituximab.
Laboratory evidence of prior infection of Hepatitis B and Hepatitis C.
Initiation of an exercise program within 4 weeks of screening visit or initiation of an exercise program during the study.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/20/2008