Clinical trial NCT05115903: Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis
Official title: A Prospective, Randomized Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Axial Spondyloarthritis
Keywords: spondyloarthritis
TNF inhibitors
tapering
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-11-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Weeks 12, 24, 36, and 48
Secondary outcomes:
measure: Proportion of patients experiencing a disease flare by ASDAS or BASDAI
timeFrame: Up to Week 48
measure: Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Up to Week 48
measure: Mean quality of life in the tapered-dose arm vs. the standard-dose arm measured using the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire
timeFrame: Up to Week 48
measure: Proportion of patients with impaired work productivity and activity measured using the Work Productivity and Activity Impairment Questionnaire for Ankylosing Spondylitis (WPAI:SpA) questionnaire
timeFrame: Up to Week 48
measure: Proportion of patients with radiographic progression, defined as an increase in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by 2 units
timeFrame: Baseline and Week 48
measure: Proportion of patients needing concomitant medication
timeFrame: Up to Week 48
measure: Proportion of patients with any related severe adverse event
timeFrame: Up to Week 48
measure: Factors predicting flare
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University Health Network - Toronto Western Hospital
name: Robert D. Inman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Gratacos J, Pontes C, Juanola X, Sanz J, Torres F, Avendano C, Vallano A, Calvo G, de Miguel E, Sanmarti R; REDES-TNF investigators. Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Ther. 2019 Jan 8;21(1):11. doi: 10.1186/s13075-018-1772-z.
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.
citation: Lawson DO, Eraso M, Mbuagbaw L, Joanes M, Aves T, Leenus A, Omar A, Inman RD. Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2021 Jun;73(6):861-872. doi: 10.1002/acr.24184.