Discontinuation of TNF-alpha Inhibitors in Patients With Spondyloarthritis

NCT00726804 | Terminated Phase 4 DMC

• 1 other identifier: SPARTA
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 6

Brief Summary

Spondylarthropathy (SpA) comprises a group of rheumatic diseases mainly affecting the spine and sacroiliac joints. In most of the patients disease activity alternates, and some patients have symptom free periods. Tumor-Necrosis-Factor-alpha (TNF-alpha) antagonists have significantly improved the treatment options for patients with spondyloarthritis. TNF-alpha antagonist therapy is costly, implies an increased risk of infections, including reactivation of tuberculosis, and the risk of long-term adverse events, as cancer, is fully clarified. It is highly relevant to explore to which extent anti-TNF-alpha therapy can be discontinued in SpA patients without immediate relapse of disease activity. Two studies have investigated discontinuation of a TNF-alpha antagonist (infliximab and etanercept) in ankylosing spondylitis, reporting flares in the majority of patients within the 1-year follow-up period, with the longest times to relapse in patients with the lowest disease activity. The effect of adalimumab discontinuation has never been studied, and, furthermore, the effect of TNF-alpha-antagonist discontinuation has never been studied in patients with early spondyloarthritis not fulfilling the New York criteria.

Conditions

SPONDYLOARTHRITIS

Outcome Measures

Primary Outcomes (1)

• Flair-up in disease activity in axial arthritis and therapeutic response at re-starting TNF-alpha inhibitors

  40 weeks

Secondary Outcomes (1)

• Bath ankylosing spondylitis disaease activity score, Bath ankylosing spondylitis functional index, Bath ankylosing spondylitis metrology index, C-Reactive protein, MRI, biomarkers of inflammation, cartilage and bone turnover

  40 weeks

Study Arms (1)

2

OTHER

Drug: Discontinuation of TNF-alpha inhibitor and re-starting it if flare-up in disease activity (etanercept or adalimumab)

Interventions

Discontinuation of TNF-alpha inhibitor and re-starting it if flare-up in disease activity (etanercept or adalimumab) DRUG

Discontinuation of infusion infliximab (Remicade) 3-5mg/kg every 6-8 week, injection of etanercept (Enbrel) 25 mg x 2/week or injection of adalimumab (Humira) 40 mg eow.

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 12 months of treatment with infliximab, etanercept and adalimumab.
• Diagnosis of spondylarthritis according to the European Spondyloarthritis Study Group (ESSG) criteria or modified New York Criteria
• No clinical active disease, defined as a BASDAI score \< 4.
• Among other issues: Age \>18 years; written informed consent, adequate birth control; no contraindications for anti-TNF-alpha-therapy

You may not qualify if:

• Treatment with disease modifying anti-rheumatic drugs within 4 weeks before screening
• Oral, intraarticular, intramuscular or intravenous glucocorticoid within 4 weeks before screening
• Pregnancy or lactation
• HIV, hepatitis B or C, tuberculosis, other infections
• Malignancies
• Other serious concomitant diseases (uncontrolled/severe kidney, liver, haematological, gastrointestinal, endocrine, cardiovascular, pulmonary, neurological ore cerebral disease (including demyelinating disease)
• Contraindications to anti-TNF-alpha-therapy
• Contraindications to MRI

Sponsors & Collaborators

• Glostrup University Hospital, Copenhagen: lead

Study Sites (6)

Glostrup Hospital

Copenhagen, 2600, Denmark

Location

Glostrup Hospital

Copenhagen, 2650, Denmark

Location

Gentofte Hospital

Copenhagen, 2730, Denmark

Location

Gentofte Hospital

Copenhagen, 2900, Denmark

Location

Gråsten Gigthospital

Gråsten, Denmark

Location

Vejle Sygehus

Vejle, Denmark

Location

MeSH Terms

Conditions

Spondylarthritis

Interventions

Etanercept; Adalimumab

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Mikkel Østergaard, Professor

  Department of rheumatology, Glostrup Hospital, Copenhagen

  STUDY CHAIR

• Susanne J Pedersen, MD

  Department of rheumatology, Glostrup Hospital, Copenhagen

  STUDY CHAIR

• Inge J Sørensen, MD, PhD

  Department of rheumatology, Glostrup Hospital, Copenhagen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: August 1, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: August 19, 2015

Record last verified: 2015-08

Locations

DK (6)