Clinical trial NCT00726804: Discontinuation of TNF-alpha Inhibitors in Patients With Spondyloarthritis
Official title: Discontinuation of TNF-alpha Inhibitors in Spondylarthritis Patients With Low Disease Activity, and Re-initiation of Therapy if Disease Flares
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: SPONDYLOARTHRITIS
Lead sponsor: Glostrup University Hospital, Copenhagen
Sponsor class: OTHER
First posted: 2008-08-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Flair-up in disease activity in axial arthritis and therapeutic response at re-starting TNF-alpha inhibitors
timeFrame: 40 weeks
Secondary outcomes:
measure: 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
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Glostrup Hospital
city: Copenhagen
country: Denmark
facility: Glostrup Hospital
city: Copenhagen
country: Denmark
facility: Gentofte Hospital
city: Copenhagen
country: Denmark
facility: Gentofte Hospital
city: Gråsten
country: Denmark
facility: Gråsten Gigthospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
Study officials:
affiliation: Department of rheumatology, Glostrup Hospital, Copenhagen
name: Mikkel Østergaard, Professor
role: STUDY_CHAIR
affiliation: Department of rheumatology, Glostrup Hospital, Copenhagen
name: Susanne J Pedersen, MD
role: STUDY_CHAIR
affiliation: Department of rheumatology, Glostrup Hospital, Copenhagen
name: Inge J Sørensen, MD, PhD
role: STUDY_CHAIR
References: