Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis

NCT05115903 | Unknown Phase 4

• 1 other identifier: 21-5211
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Axial Spondyloarthritis

Keywords

spondyloarthritis; TNF inhibitors; tapering

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (8)

• Proportion of patients experiencing a disease flare by ASDAS or BASDAI

  Up to Week 48

• Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)

  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

  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

  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

  Baseline and Week 48

Study Arms (2)

Tapered doses of TNFi

EXPERIMENTAL

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

Standard dose of TNFi

ACTIVE COMPARATOR

Stable doses of TNFi according to the approved summary of product characteristics for biologic agents used in axial spondyloarthritis

Drug: Standard dose of TNFi

Interventions

Tapered doses of TNFi DRUG

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

Also known as: 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%)

Tapered doses of TNFi

Standard dose of TNFi DRUG

To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab)

Also known as: 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

Standard dose of TNFi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network - Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (7)

• Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002 Apr 6;359(9313):1187-93. doi: 10.1016/s0140-6736(02)08215-6.

  PMID: 11955536 BACKGROUND

• van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, Dougados M, Reveille JD, Wong RL, Kupper H, Davis JC Jr; ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006 Jul;54(7):2136-46. doi: 10.1002/art.21913.

  PMID: 16802350 BACKGROUND

• Inman RD, Davis JC Jr, Heijde Dv, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008 Nov;58(11):3402-12. doi: 10.1002/art.23969.

  PMID: 18975305 BACKGROUND

• Navarro-Compan V, Plasencia-Rodriguez C, de Miguel E, Balsa A, Martin-Mola E, Seoane-Mato D, Canete JD. Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. Rheumatology (Oxford). 2016 Jul;55(7):1188-94. doi: 10.1093/rheumatology/kew033. Epub 2016 Mar 21.

  PMID: 26998860 BACKGROUND

• 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.

  PMID: 30621746 BACKGROUND

• 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.

  PMID: 32536984 BACKGROUND

• 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.

  PMID: 32166872 BACKGROUND

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylarthritis

Interventions

Etanercept; Adalimumab; Certolizumab Pegol; golimumab; Infliximab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments

Study Officials

• Robert D. Inman, MD

  University Health Network - Toronto Western Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 10, 2021
• Study Start: December 1, 2021
• Primary Completion: July 1, 2024
• Study Completion: August 1, 2024
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)