Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis (BIOTAPE)

January 15, 2024 updated by: Robert Inman, University Health Network, Toronto

A Prospective, Randomized Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis

Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a 48-week randomized, controlled, open-label, non-inferiority trial of patients with radiographic or non-radiographic axial spondyloarthritis. The study will include 156 patients with inactive disease or low disease activity (LDA) for at least 6 months on a TNFi at the time of randomization.

Participants will be randomized using a 1:1 ratio to either the tapered-dose arm or the standard-dose arm of TNFi. Progressive tapering of TNFi according to a predefined protocol will be allowed as long as the patient is able to maintain inactive disease or LDA during the study period. We hypothesize that, in patients with 6 months or more of inactive or low-activity axial spondyloarthritis, tapered-dose TNFi are non-inferior to standard-dose TNFi in sustaining the disease state for at least 1 year.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • University Health Network - Toronto Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult axSpA patients satisfying the 2009 Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria
  • Currently enrolled in the SPARCC Program with successful completion of standard data collection protocol in the Spondylitis Clinic of UHN-Toronto Western Hospital
  • Have sustained inactive disease or LDA with an ASDAS of <2.1 or BASDAI <4 for at least 6 months
  • On a stable dose of a TNFi (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab)
  • Must not be pregnant

Exclusion Criteria:

  • Adults axSpA patients with active extra-articular manifestations such as inflammatory bowel disease, psoriasis, and/or uveitis
  • Have comorbidities that may preclude clinical assessment (i.e. fibromyalgia or other chronic pain syndromes; chronic inflammatory diseases other than axSpA)
  • Have diagnosed psychiatric or personality disorders
  • Pregnant
  • Not enrolled in the Spondyloarthritis Research Consortium of Canada (SPARCC) Program

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tapered doses of TNFi
Tapering of TNFi through standardized increases in the dosing interval between drug administration. The tapering dose intervals for each TNFi are designed to decrease the dose from baseline by 75% for 12 weeks, 50% for 24 weeks, and 25% for 12 weeks
Drug: Tapered doses of TNFi
To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab) at increasing dose intervals as specified
Other Names:
  • etanercept 50 mg every 10 days (75% of baseline dose), 14 days (50%), 30 days (25%)
  • adalimumab 40 mg every 3 weeks (75%), 4 weeks (50%), 16 weeks (25%)
  • certolizumab pegol 200 mg 3 weeks (75%), 4 weeks (50%), 16 weeks (25%)
  • golimumab 50 mg every 6 weeks (75%), 8 weeks (50%), 16 weeks (25%)
  • infliximab 5 mg/kg every 8 weeks (75%), 12 weeks (50%), 16 weeks (25%)
Active Comparator: Standard dose of TNFi
Stable doses of TNFi according to the approved summary of product characteristics for biologic agents used in axial spondyloarthritis
Drug: Standard dose of TNFi
To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab)
Other Names:
  • etanercept 50 mg every 7 days
  • adalimumab 40 mg every 2 weeks
  • certolizumab pegol 200 mg every 2 weeks
  • golimumab 50 mg every 4 weeks
  • infliximab 5 mg/kg every 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients able to maintain inactive disease or low disease activity, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 to 2.1 or Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) of <4 on tapered-dose TNFi
Time Frame: Weeks 12, 24, 36, and 48

The ASDAS and BASDAI are measures of axial spondyloarthritis disease activity for the past week. The ASDAS has 5 components scored from 0 to 10 (none to very severe). The following formula is used to compute for the ASDAS: (0.121 × back pain score) +(0.058 × score for duration of morning stiffness) + (0.11 × patient global assessment score) + (0.073 × peripheral pain/swelling score) + (0.579 × log(CRP+1)). The scores range from 0 (no disease activity) to infinity (being determined by the level of CRP). The disease is considered inactive if the final score is <1.3, and low if <2.1.

The BASDAI consists of six items, with each item being scored from 0 ("none") to 10 ("very severe"). The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. A BASDAI of <4 indicates inactive or low disease.

As opposed to ASDAS, BASDAI does not include CRP in its formula. Either ASDAS or BASDAI is acceptable in clinical practice.
Weeks 12, 24, 36, and 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients experiencing a disease flare by ASDAS or BASDAI
Time Frame: Up to Week 48

Flare is defined in this study as either of the following:

  1. loss of inactive disease or LDA (ASDAS ≥2.1 or BASDAI ≥4) - see definitions above
  2. minimal clinically important worsening, defined as an increase in ASDAS by ≥0.9 on two consecutive visits
Up to Week 48
Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)
Time Frame: Up to Week 48
The BASFI measures the degree of functional limitation. It is composed of a set of 10 questions relating to activities during the past week. Each item is scored from 0 ("easy") to 10 ("impossible"). The final BASFI is the mean of the 10 scores with the total score ranging from 0 to 10. Lower scores indicate better physical function.
Up to Week 48
Mean quality of life in the tapered-dose arm vs. the standard-dose arm measured using the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire
Time Frame: Up to Week 48
The ASQoL measures health-related quality of life (HRQoL) in subjects with axial spondyloarthritis. The final ASQoL score ranges from 0 to 18, with higher scores indicating worse HRQoL.
Up to Week 48
Proportion of patients with impaired work productivity and activity measured using the Work Productivity and Activity Impairment Questionnaire for Ankylosing Spondylitis (WPAI:SpA) questionnaire
Time Frame: Up to Week 48
The WPAI:SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the effect of SpA on work productivity while at work, and the effect of SpA on activities outside of work. The 4 scores derived include percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage for each sub-scale ranges from 0 to 100. Higher scores indicate greater impairment and less productivity.
Up to Week 48
Proportion of patients with radiographic progression, defined as an increase in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by 2 units
Time Frame: Baseline and Week 48
The mSASSS measures the sum of the lumbar and cervical spine score from 0 (no change) to 72 (progression). The score is derived from grading of the anterior aspect of the vertebral bodies of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1). Grading is as follows: 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable).
Baseline and Week 48
Proportion of patients needing concomitant medication
Time Frame: Up to Week 48
Concomitant medications will include NSAIDs, conventional synthetic DMARDs, and/or targeted synthetic DMARDs used during the study period
Up to Week 48
Proportion of patients with any related severe adverse event
Time Frame: Up to Week 48
Severe adverse event, defined as serious infections requiring systemic antibiotic use and/or hospitalization assessed to be at least possibly related to TNFi use or withdrawal
Up to Week 48
Factors predicting flare
Time Frame: Up to Week 48
Factors including but not be limited to the following: sex, human leukocyte antigen (HLA)-B27 status, disease duration, duration of remission, ASDAS at the start of taper, and MRI findings at the time of taper
Up to Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Robert D. Inman, MD, University Health Network - Toronto Western Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2021

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

October 28, 2021

First Submitted That Met QC Criteria

November 8, 2021

First Posted (Actual)

November 10, 2021

Study Record Updates

Last Update Posted (Actual)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 15, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-5211

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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