Ankylosing Spondylitis(AS)
Conditions
Keywords
Ankylosing Spondylitis, Golimumab, Simponi, Anti-TNF alpha, EPCs, Vascular stiffness
Brief summary
1. To determine the effect of Golimumab treatment on the number and function of Endothelial Progenitor Cells (EPCs) in Ankylosing Spondylitis(AS) patients as a possible mechanism for the effect of this treatment on endothelial function. 2. To ascertain the effect of Golimumab treatment on , carotid intima-media thickness, vascular stiffness in Ankylosing Spondylitis(AS) patients as measured by pulse wave velocity (PWV) and Augmentation index (AIx). 3. To assess the clinical efficacy of Golimumab in Chinese Ankylosing Spondylitis(AS) patients according to ASAS response criteria at month 3, 6 and 12. 4. To perform cost-effectiveness and cost-utility analyses of the Golimumab in Ankylosing Spondylitis(AS) patients, using clinic-base data.
Detailed description
This study will provide important data on the pathogenesis of vascular damage and possible mechanism by which potent anti-inflammatory treatment may reduce cardiovascular risk in Ankylosing Spondylitis(AS) patients. Fifty patients with Ankylosing Spondylitis(AS) will be randomized to receive either Golimumab or Placebo for 12 months. Patients randomized to Placebo with worsening disease activity (failure to achieve Assessment of SpondyloArthritis international Society (ASAS20)) at week 24 will be permitted to escape to open-label Golimumab. Clinical assessment, intima-media thickness, vascular stiffness and endothelial progenitor cells will be performed at baseline, 6 and 12 months.
Interventions
DRUGSimponi
Golimumab 50mg monthly
OTHER0.9ml sodium chloride
0.9ml sodium chloride
Sponsors
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men or women, 18 years of age or older * Fulfilled the modified New York diagnostic criteria for Ankylosing spondylitis (AS)for more than 3 months * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 (0-10 point scale), Pain visual analog scale(VAS) ≥ 4 (0-10cm scale) * Inadequate response to at least two Nonsteroidal Antiinflammatory Drugs (NASID) on highest recommended doses for 3 months or unable to receive full 3-month course because of intolerance,toxicity or contraindications * Normal Chest X-ray within 3 months before baseline * Purified Protein Derivative(PPD) negative, or Latent Tuberculosis (TB) patients were required therapy for Tuberculosis (TB) before or simultaneously with first dose of study agent
Exclusion criteria
* Complete ankylosis of the spine * Concurrent with other inflammatory rheumatic disease * Serious infection (treatment with IV-infective) within 2 months before randomization * Active Tuberculosis (TB) or recent contact with a person with active Tuberculosis (TB) * An opportunistic infection within 6 months of screening * Known history of Hepatitis, Human Immunodeficiency Virus (HIV), Malignancy, a transplanted organ, multiple sclerosis, congestive heart failure * Currently on systemic immunosuppressives, DMARDS (other than Methotrexate, Sulfasalazine , or Hydroxychloroquine), or Leflunomide within 4 week before first study agent * Any previous use of Alefacept, Efalizumab, Rituximab, Golimumab or Natalizumab * Use of cytotoxic drugs, received intra-articular, intramuscular, or intravenous corticosteroids in the past 4 weeks before screening * Clinically significant renal disease (serum creatinine level ≥ 270µmol/L), alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN) * Hemoglobin level \< 8.5gm/dl, a white blood cell count \< 3.5x 109/liter, a platelet count \< 100x 109/liter * Female of childbearing potential, unwilling to use adequate contraception during the study * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Golimumab treatment on the progression of subclinical atherosclerosis | Month 12 | Effect of Golimumab treatment on the progression of subclinical atherosclerosis at 12 months compared with baseline as evaluated by Intima-Media Thickness (IMT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Golimumab treatment on the changes in arterial stiffness | Month 12 | Effect of Golimumab on changes in arterial stiffness at 12 months compared with baseline as evaluated by Pulse Wave Velocity and Augmentation Index. |
| Changes on the number and function of Endothelial Progenitor Cells in Ankylosing Spondylitis before and after 1 year of Golimumab compared with baseline. | Month 12 | The number and function of EPCs before and after golimumab will be assessed using Wilcoxin-sign rank test |
| To correlate the changes in Intima-Media Thickening, Pulse Wave Velocity, Augmentation Index and Endothelial Progenitor Cells with the changes in markers of disease activity. | Month 12 | Correlation between the change in disease activity markers (BASDAI, ESR, CRP, and MRI global activity score) and the change in IMT, PWV and AIx and EPC number will be assessed using Spearman's test |
| Incremental cost-utility ratio of the treatment of Golimumab. | Month 12 | Utility will be assessed using the EuroQol 5D (EQ5D) and the Short-Form 36 (SF-36), at baseline and every visit.Utility is used to calculate quality-adjusted life years (QALYs). The incremental cost-utility ratio expressed as (annual costs of golimumab treatment - annual costs of placebo treatment) / additional QALY gain by golimumab treatment is calculated. |
Countries
China
Outcome results
None listed