Discontinuation of TNF-alpha Inhibitors in Patients With Spondyloarthritis

Study Overview
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Brief Summary
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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.

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

Conditions
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SPONDYLOARTHRITIS

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |