Abatacept for Patients With Inflammatory Arthritis Associated With Sjögren's Syndrome: an Open-Label Phase II Study

Sjogren's Syndrome (SS) is a common systemic autoimmune disease, including primary and
secondary form. About 30% of RA are associated with sSS (1) Tumor necrosis factor alpha
inhibitors (TNFa-Is) have been tried in this population without success. Abatacept
(CTLA4-Ig) is comprised of the ligand-binding domain of CTLA4 plus human immunoglobulin and
represents a novel therapeutic costimulation blocker that modulates the signal required for
full T cell activation. Studies have shown that activated CD4 T cells play a role in the
pathogenesis of SS, indicating Abatacept might be a useful therapeutic intervention in SS.
Subjects who are receiving non-biologic immunosuppressive medications consisting of
hydroxychloroquine, methotrexate (MTX), sulfasalazine, or leflunomide, at the time of
enrollment will remain on these medications without dosage alteration. Efficacy and Safety
data will be collected at the time of each clinic visit. The treatment closing date will
occur 6 months after enrollment of each subject. Subjects will be followed at 1, 2, 3, 4, 5,
and 6 months. Laboratory studies associated with the clinical trial will test potential
autoantibody production for systemic autoimmune diseases.

Inclusion Criteria:

1. Diagnosis of Sjogren's Syndrome

2. Patients are at least 18 years or older

3. Patients should have either pSS and/or sSS associated with RA, and must have active
moderate to severe inflammatory arthritis as defined by painful joint counts (≥5) and
swollen joint counts (≥5), or DAS28 scores>3.2.

4. One non-biologic DMARD will be permitted.

5. These patients will be willing and able to comply with treatment and follow-up
procedures.

6. These patients will be willing and able to provide written informed consent.

7. Both women and men of child bearing age must be willing to use an effective means of
birth control while receiving treatment throughout participation in this study.
Effective contraception methods include abstinence, oral contraceptives (birth
control pills), IUD, diaphragm, Norplant, approved hormone injections, condoms, or
medical sterilization.

Exclusion Criteria:

1. Patients will be excluded if they have a concomitant disorder requiring systemic
glucocorticoid (GC) therapy (prednisone >10 mg daily or GC equivalent), have
organ-threatening features, and have any investigational drug including biologics
within 28 days of study entry.

2. History of cancer or diabetes mellitus

3. Use of tricyclic antidepressants or anticholinergics

4. Evidence of active infection or chronic infection including human immunodeficiency
virus (HIV), tuberculosis (TB), hepatitis C, or a positive hepatitis B surface
antigen.

5. Patients with latent TB if not treated with isoniazid for at least 4 weeks prior to
receiving the study drug

6. Radiographic evidence of COPD, emphysema, and/or interstitial lung disease.

7. Subjects who are pregnant or who are nursing infants

8. Patients with cytopenia: platelet count <80,000/mm3, absolute neutrophil
count<1500/mm3, hematocrit < 20%.

9. Patients with renal insufficiency defined by a serum creatinine of greater than or
equal to 2.0 mg/dL or creatinine clearance of less than or equal to 35 ml/min.

10. Use of illegal drugs.

11. A live vaccination fewer than 4 weeks before enrollment