The purpose of this study is to assess the safety and efficacy of subcutaneous abatacept in 10 patients seven years of age and older with refractory JDM.

JDM is a chronic systemic autoimmune disease with a predominance of muscle and skin inflammation of unknown etiology and varying prognosis. Children with JDM unresponsive to corticosteroids or other immunosuppressive medications face poor clinical and functional outcome and suffer various sequelae of the disease. Abatacept is a fully human soluble recombinant protein consisting of the cytotoxic T cell Lymphocyte Antigen-4 (CTLA4) fused with Fc region of human IgG1 that has been modified to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept binds specifically to the CD80 (B7-1) and CD86 (B7-2) molecules, those expressed on antigen-presenting cells (APCs). Upon engagement of CTLA4 to CD80 or CD86, the resultant inhibition of signal transduction inhibits T cell activation.. The rationale for use of Abatacept in the therapy of JDM includes the expression of CTLA4, CD28, CD86, and CD40 on inflammatory cells of muscle biopsies of patients with DM, as well as CTLA4 and CD28 on muscle cells.

A patient's participation in this study will last approximately 24 weeks with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. Each injection will be given on an outpatient basis.

There will be a total of 6 study visits. All participants will visit the outpatient clinic at selected time points for muscle strength testing, a physical exam, disease activity measurements, blood and urine collection, and muscle MRI; they will also be asked to complete several questionnaires. During the study, participants will be monitored closely for improvement or worsening of their disease and for serious drug related side effects.

Eligibility Ages Eligible for Study: ≥ 7 years and older Genders Eligible for Study: Both Race/Ethnic Backgrounds Eligibility for Study: No restrictions

Inclusion Criteria:

1. Adults with definite or probable JDM and pediatric patients 7 years of age and older with definite or probable JDM.

2. Body weight of at least 25 kg (or at least 55 lbs) and age ≥ 7 years of age.

3. Patients must reside within the United States or Canada.

4. Refractory myositis, as defined by the intolerance to or an inadequate response to corticosteroids plus an adequate regimen of at least one other immunosuppressive agent, including azathioprine, methotrexate, IVIG, mycophenolate mofetil, cyclophosphamide, tacrolimus or cyclosporine A, or a biologic therapy. The definition of intolerance is: side effects that require discontinuation of the medication or an underlying condition that precludes the further use of the medication.

5. At least moderately active disease as documented by:

   • MD global VAS with a minimum value of 2.5 cm on a 10 cm scale AND
   • At least 2 other abnormal core set measures listed below:

6. Therapy with prednisone or another glucocorticoid is required, unless there is documented intolerance in the medical record or a medical condition that contraindicates further use of prednisone. The prednisone dose must be stable for at least 4 weeks prior to the screening visit.

7. Background therapy with at least 1 non-corticosteroid immunosuppressive agent is required at a stable dose for at least 6 weeks prior to the screening visit unless there is documentation that the patient is intolerant, which is defined as side effects that require discontinuation of the medication(s) or an underlying condition that precludes the further use of the IS medication.

8. If an immunosuppressive agent was discontinued prior to the screening visit then there must be a:

   • 4 week washout for prednisone or methotrexate
   • 8 week washout for any other IS agent
   • For discontinuation of biologic therapies, a washout of 5 terminal half lives

9. If on hydroxychloroquine or colchicine, the dose should be stable for 6 weeks prior to Visit 1.

10. If on statin or fibric acid derivative agents, the dose should be stable for 6 weeks prior to Visit 1.

11. Ability of patient or parent to complete self-report questionnaires.

12. Men and women of reproductive potential must agree to use a reliable method of birth control during the 24 week duration of the trial described in the reproductive risks section of this protocol (section 4.3). They must also agree to use a reliable method of birth control for 100 days after the last dose of study drug is administered.

13. Patients must agree to forgo immunization with a live vaccine during the course of the study or within 3 months after discontinuation.

14. Patients must have a letter from the referring rheumatologist or specialist supervising the care of the JDM, agreeing to the patient's participation in the study and to continuing to provide care for the patient, including emergency care during the trial.

Core Set Measures:

• An MMT-8 score that is no greater than 125/150
• Patient/Parent Global VAS with a minimum value of 2.0 cm on a 10cm scale
• CHAQ/HAQ disability index with a minimum value of 0.25
• Elevation of at least one of the muscle enzymes [which includes creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] at a minimum level of 1.3 x the upper limit of normal.
• Global extra-muscular disease activity score with a minimum value of 2.0 cm on a 10 cm VAS scale

Exclusion Criteria:

1. Drug-induced myositis (myositis in patients taking medications known to induce myositis-like syndromes, including, but not limited to, statin agents, fibric acid derivatives, and colchicine).
2. Juvenile polymyositis; inclusion body myositis; cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer except basal or squamous cell skin cancer or carcinoma in situ of the cervix if at least 5 years since excision
3. Myositis in overlap with another connective tissue disease (CTD) that precludes the accurate assessment of a treatment response (for example, difficulty in assessing muscle strength in a scleroderma patient with associated myositis)
4. History of receiving a live vaccine 4 weeks prior to initiation of study treatment
5. Joint disease, severe calcinosis, or other musculoskeletal condition, which precludes the ability to quantitate muscle strength.
6. Wheelchair bound patients.
7. Known hypersensitivity to abatacept or prior receipt of abatacept
8. Concomitant illness that would prevent adequate patient assessment or in the investigators opinion pose an added risk for study participants:
9. Recurrent or chronic infections, including HIV, tuberculosis, hepatitis B and C, or TB infection, including contact with a household contact with active tuberculosis (TB) and who did not receive appropriate and documented prophylaxis for TB. (a documented negative Hepatitis B surface antigen and Hepatitis C antibody completed at the screening visit or within 6 weeks prior to screening visit is required)
10. Have had symptomatic herpes zoster or herpes simplex infection (not including simple oral HSV lesions) within 12 weeks prior to entry or during screening period
11. Have a history of disseminated/complicated herpes zoster (for example, multi-dermatomal involvement, ophthalmic zoster, central nervous system (CNS) involvement, post-herpetic neuralgia)
12. Known liver disease (i.e. cirrhosis or other conditions compromising the synthetic function of the liver)
13. Disorders that would preclude accurate assessment of neuromuscular function
14. Cardiomyopathy or arrhythmias that in the investigators opinion poses an additional risk for study participants
15. New York Heart Association Classification III or IV for congestive heart failure
16. Psychiatric illness that precludes compliance or neuromuscular assessment
17. Serum creatinine > 2.0mg/dl
18. Pregnant females or nursing mothers
19. Life threatening illness that would interfere with the patient's ability to complete the study.
20. Known or suspected history of drug or alcohol abuse within the past 6 months as determined by the medical record or patient interview
21. Anticipated poor compliance
22. Participation in another clinical experimental therapeutic study within 30 days of screening visit.
23. 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.
24. Low total WBC <2.000, platelets < 100,000/mm3; hemoglobin <10 gm/dl
25. History of recurrent infection including active skin infections with calcinosis
26. Subjects with a history of cancer in the last 5 years
27. Subjects who have at any time received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the day 1 dose of study drug, including waiting until CD19 returns to a detectable level and IgG level is within normal limits (normal serum levels of IgG per reference lab: 7-9 years ≥572 mg/dl, 10-11 yrs ≥698 mg/dl, 12-13 yrs ≥759 mg/dl, 14-15 yrs ≥716 mg/dl,16-19 yrs ≥549 mg/dl, >19 yrs ≥700 mg/dl) for those patients who have received rituximab
28. Concomitant treatment with anti-TNF therapies, rituximab or anakinra or other biologic therapies.
29. Initiation of colchicine and hydroxychloroquine as new drugs during study participation is not allowed.
30. Initiation of statins or fibric acid derivatives during study participation is not allowed.
31. Initiation of an exercise program within 4 weeks of the screening visit. Only a stretching program may be initiated during the study (See section 5.4 Other Restrictions)
32. Prisoners or subjects who are involuntarily incarcerated.
33. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

week 0 to week 24

Non-randomized open label study design