Clinical trial NCT03880968: Treat-to-Target Strategy With Etanercept for Ankylosing Spondylitis
Official title: Treat-to-Target Strategy With Etanercept for Ankylosing Spondylitis: a Prospective, Randomized Multicentric Study on Disease Activity Guided Etanercept Tapering or Discontinuation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spondylitis, Ankylosing
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
name: First Affiliated Hospital of Wenzhou Medical University
name: Affiliated Hospital of Jiaxing University
name: Shaoxing Second Hospital
name: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Wenzhou Central Hospital
name: Zhejiang Provincial People's Hospital
name: Shaoxing People's Hospital
First posted: 2019-03-19
Enrollment: 311
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with AS were recruited in this study. Eligible patients were aged between 18 years old and 65 years old, and were diagnosed with AS according to 1984 revised New York classification criteria. Only patients meet both inclusion and exclusion criteria were included.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative flare rates at week 48 with different tapering or discontinuation strategies
timeFrame: 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: wuhx8855@sina.com
name: Huaxiang Wu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang T, Zhu J, He D, Chen X, Wang H, Zhang Y, Xue Q, Liu W, Xiang G, Li Y, Yu Z, Wu H. Disease activity guided stepwise tapering or discontinuation of rhTNFR:Fc, an etanercept biosimilar, in patients with ankylosing spondylitis: a prospective, randomized, open-label, multicentric study. Ther Adv Musculoskelet Dis. 2020 Jun 2;12:1759720X20929441. doi: 10.1177/1759720X20929441. eCollection 2020.