Abatacept for the Treatment of Giant Cell Arteritis

Inclusion Criteria:

1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA A patient will be said to have GCA by meeting 3 of 5 of the following modified ACRcriteria for the classification of GCA in which 1 of the 3 must consist of criteria 4 or 5:

2. Age at disease onset ≥ 50 years.

3. New onset or new type of localized pain in the head.

4. ESR of > 40 mm in the first hour by the Westergren method or CRP measurementabove the laboratory normal limit.

5. Temporal artery abnormality (i.e., temporal artery tenderness to palpation ordecreased pulsation, unrelated to arteriosclerosis of cervical arteries).

6. Temporal artery or large vessel biopsy showing vasculitis characterized by apredominance of mononuclear cell infiltration or granulomatous inflammation,usually with multinucleated giant cell or an abnormal temporal arteryultrasound showing features consistent with active giant cell arteritis ("halosign") or characteristic changes of large vessel stenosis or aneurysm byarteriography.

7. GCA with evidence of active disease (defined below) present within the past 8 weeks.

8. They must be willing and able to comply with treatment and follow-up procedures.

9. Both women and men who are of child-bearing potential must be willing to use aneffective means of birth control while receiving treatment through this study.Effective contraception methods include abstinence, surgical sterilization of eitherpartner, barrier methods such as diaphragm, condom, cap or sponge, or hormonalcontraception.

10. They must be willing and able to provide written informed consent.

Exclusion Criteria:

1. Evidence of a recent acute infection defined as:

• Any acute infection within 60 days prior to randomization that requiredhospitalization or treatment with parenteral antibiotics.

• Any acute infection within 30 days prior to randomization that required oralantimicrobial or antiviral therapy.

2. Patients with history of chronic or recurrent bacterial infection (such as chronicpyelonephritis, osteomyelitis, and bronchiectasis etc.).

3. Patients with a history of recurrent herpes zoster (more than 1 episode) ordisseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex,or ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolvedmore than 60 days prior to screening.

4. Patients with a history of systemic fungal infections (such as histoplasmosis,blastomycosis, or coccidiomycosis).

5. Patients with a history of primary immunodeficiency.

6. Patients at risk for tuberculosis (TB) defined as follows:

• Current clinical, radiographic or laboratory evidence of active TB, even ifcurrently being treated. Chest x-rays (posterior/anterior and lateral) obtainedwithin the 6 months prior to screening and TB testing (IFN-gamma release assayor PPD) performed in the past month prior to screening will be accepted;however, a copy of the reports must be placed in the participant binder.

• A history of active TB unless there is documentation that the patient hadreceived prior anti-TB treatment that was appropriate in duration and typeaccording to local health authority guidelines.

• Patients with a positive TB screening test indicative of latent TB will not beeligible for the study unless they: i. Have no evidence of current TB based on chest x-ray performed during thescreening period and by history and physical exam, and ii. They are currentlybeing treated for latent TB or the site has documentation of successful priortreatment of latent TB. Treatment regimens should be dictated by localguidelines as long as the treatment dose and duration meet or exceed localhealth authority guidelines. If permitted by local guidelines regardingtreatment with biologic medications, patients with latent TB may be randomizedprior to completion of treatment as long as they have completed at least 4weeks of treatment and they have no evidence of current TB on chest x-ray atscreening.

7. Patients who are pregnant or who are nursing infants.

8. Inability to comply with study guidelines.

9. Cytopenia: platelet count <80,000/mm3, total White Blood Count (WBC) < 3,000/mm3 (3x 109/L) absolute neutrophil <1500/mm3, hematocrit < 20%.

10. Renal insufficiency defined by a creatinine clearance of less than or equal to 20ml/min.

11. AST or ALT > 3 times above normal laboratory range.

12. Other severe, progressive, or uncontrolled disease that in the investigator'sopinion could prevent a patient from fulfilling the study requirements or that wouldincrease the risk of study participation.

13. Patients who have a present malignancy or previous malignancy within the last 5years prior to screening (except documented history of cured non-metastatic squamousor basal cell skin carcinoma or cervical carcinoma in situ). Patients who had ascreening procedure that is suspicious for malignancy, and in whom the possibilityof malignancy cannot be reasonably excluded following additional clinical,laboratory or other diagnostic evaluations.

14. Receipt of an investigational agent or device within 30 days prior to enrollment.

15. A live vaccination within 3 months before randomization.

16. Patients on non-biologic immunosuppressants must discontinue these medicationsbefore randomization (azathioprine, mycophenolate mofetil, mycophenolic acid,leflunomide, hydroxychloroquine, cyclosporin, tacrolimus, or other conventionalimmunosuppressive agent).

17. Patients who had received an alkylating agent such as cyclophosphamide mustdiscontinue these medications at least 8 weeks before randomization.

18. Patients who have been treated within 4 weeks of randomization with etanercept orwithin 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.

19. Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.

20. Patients who have been treated within 4 weeks of randomization with anakinra.

21. Patients who have received prior treatment with rituximab within the past 6 monthsprior to randomization.

22. Patients who have received prior treatment with abatacept or CTLA4-Ig.

23. Patients who will require oral or IV glucocorticoid treatment during the trial forconditions other than GCA.

24. Hypersensitivity to abatacept and/or its excipients.

25. Presence of any of the following disease processes:

• Takayasu arteritis

• Granulomatosis with polyangiitis

• Microscopic polyangiitis

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

• Polyarteritis nodosa

• Cogan's syndrome

• Behçet's disease

• Sarcoidosis

• Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimicsvasculitis

• Cryoglobulinemic vasculitis

• Systemic lupus erythematosus

• Rheumatoid arthritis

• Mixed connective tissue disease or any overlap autoimmune syndrome