Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
A Pilot Study of Abatacept for the Treatment of Patients with Diffuse Cutaneous Systemic Sclerosis.
Chakravarty1, Eliza F., Fiorentino2, David, Bennett3, Mihoko, Chung4, Lorinda
Oklahoma Medical Research Foundation, Oklahoma City, OK
Stanford, Stanford, CA
Stanford University, Palo Alto, CA
Stanford Univ Medical Center, Palo Alto, CA
Background/Purpose:
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by progressive fibrosis of skin and internal organs, vascular damage, and autoantibody production. Several lines of evidence support a role for T-cells in initiating and perpetuating disease. We performed a randomized, double-blinded placebo controlled trial to evaluate the safety and efficacy of intravenous abatacept, an inhibitor of T-cell costimulation, or placebo in patients with diffuse cutaneous systemic sclerosis (dcSSc).
Methods:
Adult subjects with dcSSc who had adequate cardiac, pulmonary (FVC>49% predicted, DLCO >39% predicted), and renal function (serum Cr <2.0) were recruited for this study. Prednisone >10 mg daily and other immunosuppressive therapies were not permitted. Subjects with active infection, history of malignancy, or infection with tuberculosis, hepatitis or HIV were also excluded. Subjects were randomized in a 2:1 double-blinded fashion to receive IV abatacept or placebo at weeks 0, 2, 4, and every 4 weeks for a total of 24 weeks. Primary outcomes were safety and the percent change in modified Rodnan Skin Score (mRSS, scale 0–51) from week 24 to baseline. Secondary clinical outcomes included change in Health Assessment Questionnaire-Disability Index (HAQ-DI), patient and physician global assessments by visual analogue scale (VAS), and pulmonary function tests (PFTs).
Results:
12 patients screened for the study: two were not eligible due to lack of peripheral venous access. 10 patients (8 women and 2 men, mean age 42.2 years) enrolled in the study. Mean disease duration from the time of the first non-Raynaud's manifestation was 4.4 (3.8) years. 7 patients were randomized to receive abatacept and 3 received placebo. At baseline, there were no significant differences in mRSS, HAQ-DI, VAS scales and PFTs between the two groups, although subjects randomized to abatacept had shorter disease duration (2.4 vs. 8.8 years, p=0.004). Compared with those receiving placebo, subjects treated with abatacept reported greater improvement in HAQ-DI and patient VAS. Numerically, patients receiving abatacept had larger improvements in absolute (-8.6 vs -2.3, p=0.059) and mean % change (-33% vs -6.2%, p=0.31) in MRSS than the placebo group (Table). No deaths or serious adverse events occurred during the study. 14 AEs (7 in each group) were reported in 9 patients: most were mild in nature. One patient, in the placebo arm, terminated the study at week 20 due to infection of a preexisting toe ulcer.
| Variable | Abatacept (n = 7) | placebo (n = 3) | p-value |
|---|---|---|---|
| Baseline | |||
| Age (year, SD) | 39.8 (11.4) | 48.6 (13.9) | 0.32 |
| % Male | 28.6 | 0 | 1 |
| % caucasian | 57.1 | 66.7 | 1 |
| Duration (raynauds) | 3.9 (3.4) | 9.2 (3.2) | 0.05 |
| Duration (1st non-raynauds) | 2.4 (1.6) | 8.8 (3.8) | 0.0042 |
| mRSS | 23.6 (6.6) | 30 (3) | 0.15 |
| HAQ-DI | 0.6 (0.8) | 1.5 (1.1) | 0.18 |
| Physician Global VAS | 37.6 (13.8) | 56.3 (5.5) | 0.57 |
| Patient Global VAS | 53 (35.8) | 61.7 (44.8) | 0.75 |
| Patient Pain VAS | 42.7 (35.3) | 53 (47.8) | 0.71 |
| FVC | 77.3 (19) | 73.3 (27.6) | 0.79 |
| DLCO | 87 (17.5) | 80.3 (24) | 0.65 |
| Outcomes | |||
| Change in HAQ-DI | -0.04 (0.2) | 0.25 | 0.56 |
| Absolute change in mRSS | -8.6 (7.5) | -2.3 (15.0) | 0.059 |
| % change in mRSS | -33 (29.0) | -6.2 (52.3) | 0.31 |
| Change in Physician Global | -11.9 (18.1) | -17.3 (23.2) | 0.048 |
| Change in Patient Global | -8 (7.6) | -2.7 (6.7) | 0.023 |
| Change in Patient Pain | -11.4 (8.3) | -15.0 (25.1) | 0.18 |
| Change in FVC | 1.3 (8.5) | 0.3 (8.5) | 0.72 |
| Change in DLCO | 2.0 (6.3) | -7.4 (10.7) | 0.84 |
| # Adverse events | 7 | 7 | |
Conclusion:
Blockade of T-cell costimulation with abatacept appears to be safe and may be a useful treatment for cutaneous sclerosis in patients with dcSSc. Larger, multi-center placebo-controlled studies limited to patients with early disease are necessary to further evaluate the utility of abatacept in the treatment of patients with dcSSc.
To cite this abstract, please use the following information:
Chakravarty, Eliza F., Fiorentino, David, Bennett, Mihoko, Chung, Lorinda; A Pilot Study of Abatacept for the Treatment of Patients with Diffuse Cutaneous Systemic Sclerosis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :707
DOI:
