Discontinuation of TNF-alpha Inhibitors in Patients With Spondyloarthritis (SPARTA)

Discontinuation of TNF-alpha Inhibitors in Spondylarthritis Patients With Low Disease Activity, and Re-initiation of Therapy if Disease Flares

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.

Study Overview

• Status: Terminated
• Conditions: SPONDYLOARTHRITIS
• Intervention / Treatment: Drug: Discontinuation of TNF-alpha inhibitor and re-starting it if flare-up in disease activity (etanercept or adalimumab)

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2900
    • Gentofte Hospital
  • Copenhagen, Denmark, 2600
    • Glostrup Hospital
  • Copenhagen, Denmark, 2650
    • Glostrup Hospital
  • Copenhagen, Denmark, 2730
    • Gentofte Hospital
  • Gråsten, Denmark
    • Gråsten Gigthospital
  • Vejle, Denmark
    • Vejle Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 2	Drug: Discontinuation of TNF-alpha inhibitor and re-starting it if flare-up in disease activity (etanercept or adalimumab); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Flair-up in disease activity in axial arthritis and therapeutic response at re-starting TNF-alpha inhibitors	40 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Glostrup University Hospital, Copenhagen
• Investigators: Study Chair: 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 record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: July 30, 2008
• First Submitted That Met QC Criteria: July 31, 2008
• First Posted (Estimate): August 1, 2008

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 18, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis; 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; Adalimumab
• Other Study ID Numbers: SPARTA