Spondylitis, Ankylosing
Conditions
Brief summary
Evaluate the disease activity guided tapering and discontinuation strategies of etanercept (ETN) in patients with ankylosing spondylitis (AS) in 48 weeks.
Detailed description
Ankylosing spondylitis (AS), a subset of axial spondyloarthritis (axSpA), is a chronic inflammatory disorder characterized by inflammatory back pain and predominant involvement of sacroiliac joints and spine, leading to bony fusion of vertebrae and eventually disability in some patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recognized as a first-line therapy for AS, but the overall response rates to NSAIDs are considerably unsatisfactory. With the advent of biologics, the outcomes of AS patients have been greatly improved. Biologics including tumor necrosis factor α (TNFα) inhibitors (TNFi) have been included in many recommendations for the treatment of AS. Etanercept, a recombinant human TNFα receptor, is capable of binding to TNFα and blocking its biological activities. It is effective in relieving symptoms, improving physical function, and reducing disease activity in patients with AS, and generally no severe adverse effects have been reported. However, the high expense of biologics restricts their long-term use, which urges a viable strategy to reduce the dosage of biologics while maintaining an optimal therapeutic efficacy. To investigate the stepwise tapering and discontinuation of TNFi based on disease activity in patients with AS, a 48-week, prospective, randomized, multicentric study was conducted. An etanercept biosimilar, rhTNFR:Fc (recombinant TNF receptor: Fc fusion protein, Yisaipu), which is one of the most widely used biosimilars in China, was used in this study.
Interventions
DRUGtapering or discontinuation of etanercept
Active AS patients initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients who achieved inactive disease (ASDAS\<1.3, group A) at week 12 were either assigned to sequential tapering group (A1) or discontinuation group (A2), and those who reached low disease activity (LDA) (1.3≤ASDAS\<2.1, group B) were designated to sequential tapering group (B1), delayed tapering group (B2) or discontinuation group (B3).
Sponsors
Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
First Affiliated Hospital of Wenzhou Medical University
Affiliated Hospital of Jiaxing University
Shaoxing Second Hospital
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Ningbo Medical Center Lihuili Hospital
Wenzhou Central Hospital
Zhejiang Provincial People's Hospital
Shaoxing People's Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* aged between 18 years old and 65 years old with AS, according to 1984-revised New York classification criteria. * an active disease of ASDAS with C reactive protein (ASDAS-CRP) ≥2.1. * a disease duration of 6 months to 30 years. * no exposure to biologics in recent 6 months before recruitment. Concomitant medications with NSAIDs, conventional disease modifying anti-rheumatic drugs (cDMARDs), or prednisone or a prednisone equivalent (≤10mg/day), were allowed to continue if they were maintained at a stable dose for 4 weeks or more from baseline.
Exclusion criteria
* late-stage patients with spinal fusion. * patients with severe cardiac, hepatic, renal, hematologic or endocrine diseases. * patients with a history of multiple sclerosis, current or past malignancy. * patients who were pregnant, or planning to become pregnant, or breastfeeding. * patients with active or recurrent infections, or those who required oral antibiotics 2 weeks or intravenous antibiotics 4 weeks before screening. * patients with current or past or potential tuberculosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative flare rates at week 48 with different tapering or discontinuation strategies | 48 weeks | Cumulative flare rates at week 48 with different tapering or discontinuation strategies |
Outcome results
None listed