Belimumab in Idiopathic Inflammatory Myositis

Inclusion Criteria

Subjects enrolled in the study must meet the following inclusion criteria:

• Adults >18 years of age
• Have a diagnosis of:
• definite or probable dermatomyositis (DM) or
• Definite or probable diagnosis of polymyositis (PM) with presence of one of myositis specific antibodies. In the absence of myositis specific auto-antibodies, the diagnosis of PM will require review of the muscle biopsy and adjudication by the predetermined committee of experts.
• Presence of positive autoantibody (ANA >1: 80 or RNP or SSA/SSB or any of the myositis specific autoantibody: antisynthetase autoantibodies (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS), anti-SRP, anti-Mi-2, anti-p140).
• Have refractory IIM as defined by inadequate response or intolerance to at least 3 months of glucocorticoids and/or at least one other immunosuppressive agent, such as azathioprine, methotrexate, IVIG, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine cyclophosphamide, and Rituximab.
• Have active IIM at screening. This requires at least 3 criteria from the CSM
• Dermatomyositis patients that do not meet the MMT criteria, must have:
• a cutaneous VAS score of >3 cm on a 10 cm VAS scale (MDAAT) will be required:
• elevation of at least one muscle enzyme (creatine kinase [CK]; aldolase; lactate dehydrogenase [LDH]; alanine aminotransferase [ALT]; or aspartate aminotransferase [AST]) to a minimum level of 1.3 times the upper limit of normal,
• and 1 additional core set measure
• For patients with ≥ 7 years of IIM, muscle biopsy or muscle MRI within 4 months prior to enrollment will be required to document active myositis to avoid enrolling patients with significant index of damage/ muscle atrophy. This is not applicable to DM patients with a cutaneous VAS score of >3 cm on a 10 cm VAS scale (MDAAT).
• Have a stable background glucocorticoid therapy for at least 2 weeks prior to screening (Prednisone (or equivalent) dose 2 months prior to screening. Patients on intravenous gamma globulin (IVIG) have to be on a stable dose and frequency regimen for ≥ 3 months.
• Have the ability to understand the requirements of the study and provide written informed consent (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
• Female subjects of childbearing potential must have a negative urine pregnancy test at screening and agree to 1 of the following:
• Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 16 weeks after the last dose of study agent (Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception); or
• Consistent and correct use of 2 of acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from the study:

• Have severe muscle damage as defined by a Muscle Damage Index (MDI) > 5.0 cm using a visual analogue scale (VAS) 10.0 cm in length or evidence of severe muscle atrophy on muscle MRI.
• History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell).
• Have a history of a primary immunodeficiency
• Have a significant IgG deficiency (IgG level 1.5xULN), bilirubin (>1.25xULN, direct 35%), or INR (>1.2, excluding patients on anti-coagulant therapies) or other clinically significant abnormal laboratory value in the opinion of the investigator.
• Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0.
• Have evidence of serious suicide ris