Treat-to-Target Strategy With Etanercept for Ankylosing Spondylitis (T2TEAS)

Treat-to-Target Strategy With Etanercept for Ankylosing Spondylitis: a Prospective, Randomized Multicentric Study on Disease Activity Guided Etanercept Tapering or Discontinuation

Evaluate the disease activity guided tapering and discontinuation strategies of etanercept (ETN) in patients with ankylosing spondylitis (AS) in 48 weeks.

Study Overview

• Status: Completed
• Conditions: Spondylitis, Ankylosing
• Intervention / Treatment: Drug: tapering or discontinuation of etanercept

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.

• Study Type: Observational
• Enrollment (Actual): 311

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
inactive - half dosage tapering; Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, 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 in this arm were those who achieved inactive disease (ASDAS<1.3, group A) at week 12 and assigned to sequential tapering group (A1).	Drug: tapering 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).; Other Names: rhTNFR:Fc, Yisaipu
inactive - discontinuation; Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, 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 in this arm were those who achieved inactive disease (ASDAS<1.3, group A) at week 12 and then assigned to discontinuation group (A2).	Drug: tapering 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).; Other Names: rhTNFR:Fc, Yisaipu
low disease activity - half dosage tapering; Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, 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 in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to sequential tapering group (B1).	Drug: tapering 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).; Other Names: rhTNFR:Fc, Yisaipu
low disease activity - full dosage tapering; Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, 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 in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to delayed tapering group (B2) with extra 12 weeks of full dose ETN.	Drug: tapering 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).; Other Names: rhTNFR:Fc, Yisaipu
low disease activity - discontinuation; Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, 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 in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to discontinuation group (B3).	Drug: tapering 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).; Other Names: rhTNFR:Fc, Yisaipu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative flare rates at week 48 with different tapering or discontinuation strategies	Cumulative flare rates at week 48 with different tapering or discontinuation strategies	48 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Ningbo Medical Center Lihuili Hospital; Zhejiang Provincial People's Hospital; First Affiliated Hospital of Wenzhou Medical University; Shaoxing People's Hospital; Shaoxing Second Hospital; Wenzhou Central Hospital; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine; First Affiliated Hospital of Jiaxing University
• Investigators: Principal Investigator: Huaxiang Wu, wuhx8855@sina.com

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): September 30, 2014
• Study Completion (Actual): September 30, 2014

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 17, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 2012-13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No