Clinical trial: Infliximab (Remicade ) to Treat Dermatomyositis and Polymyositis (NCT00033891)

Eligibility criteria:
-  INCLUSION CRITERIA:

        Must be at least 18 years of age.

        Diagnosis of probable or definite polymyositis or dermatomyositis as defined by Bohan and
        Peter:

        i. Symmetrical proximal muscle weakness;

        ii. Muscle biopsy abnormalities at some time during their disease:

          1. Muscle fiber destruction;

          2. Muscle fiber regeneration;

          3. Perivascular and interstitial inflammatory infiltrates with muscle fiber destruction.

        iii. Elevation of serum creatine phosphokinase (CPK), Transaminases, lactic dehydrogenase
        (LDH) or aldolase activity;

        iv. Electromyography changes:

          1. Fibrillation potentials (on needle insertion at rest);

          2. Complex repetitive discharges (on needle insertion at rest);

          3. Positive sharp waves (on needle insertion at rest);

          4. Short duration, low amplitude complex (polyphasic) potentials on contraction.

        v. Typical skin rash. The classic skin manifestations include a purplish discoloration of
        the eyelids (heliotrope rash) or papular, erythematous, scaly lesions over the knuckles
        (Gottron s papules);

        DEFINITE: any 4 of the criteria

        PROBABLE: any 3 of the criteria

          -  Patients must have a baseline total muscle strength score of less than or equal to 120
             but not less than 80 on manual muscle testing (MMT) or at least 25% decrease in manual
             muscle strength.

          -  Ability to provide informed consent to all aspects of the study after full information
             is provided.

          -  Evidence of active disease as measured by weakness, and an elevated CK, aldolase,
             SGOT, SGPT, LDH or an active MRI. MR imaging may demonstrate signal abnormalities in
             affected muscles secondary to inflammation and edema on STIR images.

          -  Patients must be on a stable dose of prednisone equal to or less than 0.5 mg/kg/day
             for 1 month prior to the study.

          -  Patients must be on at least 7.5 mg of methotrexate weekly or at least 75 mg of
             azathioprine daily for at least 4 weeks prior to the study.

          -  Patients must not be on any other cytotoxic agents for at least 1 month prior to the
             study.

          -  Women of childbearing potential and men whose partners are of childbearing potential
             must practice an acceptable form of contraception.

          -  No prior history of treatment with monoclonal antibodies, i.e. no prior history of
             infliximab therapy.

          -  Patients with active disease despite previous treatment with at least one other
             immunosuppressive agent and/or intolerable side effects: e.g. high-dose prednisone (1
             mg/kg/day), methotrexate 12.5 to 20 mg/wk, azathioprine 100-150 mg/day, cyclosporineA
             2-2.5 mg/kg/day and cyclophosphamide 1-2 mg/kg/day.

        EXCLUSION CRITERIA:

        Patients with inclusion body myositis or cancer-related or drug-induced myopathy.

        History of hepatitis or abnormal liver function tests which do not reflect muscle disease.

        History of recurrent infections, any active acute or chronic infections requiring
        antimicrobial therapy, or serious viral (e.g. Hepatitis B positivity, herpes zoster, herpes
        simplex, HIV positivity, hepatitis C or A, CMV) or fungal infections such as
        histoplasmosis, aspergillosis, coccidiodomycosis. Patients with positive PPD who have
        cavitary lesions suspicious for active tuberculosis will be excluded. In addition, patients
        with a positive PPD who decline INH prophylaxis will be excluded. Any patients with
        suspected pneumonia, cellulitis, pneumocystis carini, and infection at central venous
        catheter site will also be excluded.

        Patients with suspicious lesions on chest radiography suggestive of an infectious or
        neoplastic condition will be excluded.

        Pregnant females, nursing mothers, or patients of childbearing age not practicing birth
        control.

        Preexisting or coexisting malignancy other than basal cell carcinoma and localized squamous
        cell carcinoma of the skin.

        Patients who have not had any recent age-appropriate malignancy screen within the past 3
        months who refuse to have said age-appropriate malignancy screening procedures prior to the
        start of the study.

        History of cerebrovascular accidents, seizure disorder, aseptic meningitis, transverse
        myelitis, central nervous system demyelinating disease such as multiple sclerosis.

        Confounding medical illness that in the judgment of the investigators pose added risk for
        study participants (e.g. chronic lung or hematological disease).

        Anemia requiring maintenance blood transfusions; leukopenia with WBC less than 3,000/ul or
        absolute neutrophil count less than 2,000/ul; platelet count less than 100,000/ul on at
        least two different occasions.

        History of (or current) autoimmune hemolytic anemia.

        Current anticoagulant therapy.

        History of lupus erythematosus (+)ANA: dsDNA, anti-Smith, anti-Ro/La and clinical
        presentation consistent with lupus erythematosus.

        Clotting/bleeding disorders history of arterial or venous thrombosis, stroke, miscarriages
        and presence of antiphospholipid antibodies, protein C or protein S deficiency along with a
        compatible history of a thrombotic event.

        History of psychiatric illness that in the opinion of psychiatric consultants would pose an
        added risk for study participants.

        History of uncontrolled diabetes mellitus.

        Prior use of infliximab.

        Current use of a TNF-blocking agent (patient has to be off for 4 weeks). Prior use of
        etanercept is accepted so long as patient has been off of it for 4 weeks.

        Allergy to murine-derived products.

        Poor venous access.

        History of live vaccinations within the past 3 months.

        History of drug abuse within the past 5 years.

        History of congestive heart failure.

        Echocardiographic evidence of dilated or hypertrophic cardiomyopathy.

        Echocardiographic evidence of valvular stenosis or regurgitation that in the judgment of
        the physician poses a risk for congestive heart failure.

        History of significant arrhythmia requiring pacing or cardioversion.

        EKG or echocardiographic evidence of ventricular hypertrophy and clinical signs of
        congestive heart failure.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 50-year-old woman comes to the clinic complaining of difficulty swallowing both liquids and solid foods, as well as occasional cough while eating.  She also has difficulty lifting her arms above her head and getting up from a chair. The weakness seems to get worse gradually. The patient has no prior medical problems and takes no medications.  Vital signs are normal.  Physical examination shows an erythematous rash on the upper eyelids. There are some red papules over joints of her hands. The rest of the physical examination is unremarkable. Antinuclear antibodies, anti-Jo-1 antibodies and anti-MDA5 antibody are positive.  Muscle biopsy shows perifascicular inflammation and atrophy of the fascicle and surrounding blood vessels.

Patient description (patient's own words): I had to go to the clinic because of difficulty swallowing all kinds of food, liquid and solid. I also sometimes cough when I eat my dinner. At only 50 year old, I had some difficulties lifting up my arms and getting up from a chair! And it's only getting worse! I never had any medical issues in the past and I'm not under any medication, I just don't get it! My vitals were normal. The physical exam showed a red rash on my upper eyelids. I also have red papules on my hands' joints. After a blood test, they told me that my antinuclear antibodies, anti-Jo-1 antibodies, and anti-MDA5 antibodies were positive.  I also did a muscle biopsy and it showed that I had an atrophy of my blood vessels around my muscle fibers and that I have an inflammation of these.

Does the patient match the trial criteria? 1