Evaluation of a Protocol for Dose Reduction in Patients With Spondylarthropathies and Clinical Remission With Anti-TNF

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that patients with Spondylarthropathies in remission under antiTNF therapy, can maintain the remission with a maintenance dose inferior to the currently recommended dose schedule.

Detailed Description
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It has been shown that the withdrawal of treatment follows with a flare of the disease in a short time after the suspension but it has not been evaluated in controlled trials if remission could be maintained with a lower dose. A multicenter, national, open-label, randomized and controlled clinical trial of 3 years duration (2 years for inclusion + 1 year follow-up) is proposed to address this issue. The study will include 190 patients with Spondylarthropathies in stable treatment with any single anti-TNF agent and compliance with criteria of clinical remission for at least 4 months. Patients will be randomized to intervention or control arm, with stratification according to the antiTNF product thet were receiving prior to inclusion. Patients will be followed with the calendar of visits recommended by the Spanish Society of Rheumatology for clinical practice. The proposed hypothesis is of non-inferiority of the experimental arm with dose reduction versus the control arm with standard treatment.

Official Title
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Evaluation of Clinical Value of Standardized Protocol for Dose-reduction in Patients With Spondylarthropathies and Clinical Remission With Anti-TNF Therapy: Open-label, Controlled, Randomized, Multicenter Trial.

Conditions
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Spondylarthropathies

Intervention / Treatment
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* Drug: Reduced doses of anti-TNF
* Drug: Stable doses of anti-TNF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years Patients with Spondylarthropathies according ASAS group criteria. Patients under treatment with anti-TNF therapy (infliximab, adalimumab, etanercept, golimumab) who present established clinical remission Patients to give their informed consent to participate in the study Exclusion Criteria: Patients with secondary Spondylarthropathies Patients with Spondylarthropathies and predominantly clinical of peripheral arthritis which receive anti-TNF therapy by peripheral symp tons. Patients with Spondylarthropathies and other associated diseases that hinders or modify the clinical evaluation of the patient (fibromyalgia, chronic inflammatory disorders…) Patients with bowel inflammatory disease Patients under chronic therapy with anti-TNF therapy who received the patterns of reduction that will be explored in the experimental group, or low doses or most spaced that those in the experimental group before study inclusion

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced doses of anti-TNF<br>Standardized schedule of reduced doses of anti-TNF, reached either through the interval spacing of administration (adalimumab, etanercept or golimumab) or reducing doses of infliximab | Drug: Reduced doses of anti-TNF<br>* Standardized schedule of reduced doses of anti-TNF, reached either through the interval spacing of administration (adalimumab, etanercept or golimumab) or reducing doses of infliximab<br>* Other names: Infliximab: 3 mg/kg / 8 weeks;|
| Active Comparator: Stable doses of anti-TNF<br>Stable doses of anti-TNF according clinical practice based on approved summary product characteristics (SPC) and SER consensus about biological therapies in Ankylosing Spondylitis and other Spondylarthropathies, except Psoriatic Arthritis | Drug: Stable doses of anti-TNF<br>* Stable doses of anti-TNF according clinical practice based on approved summary product characteristics (SPC) and SER consensus about biological therapies in Ankylosing Spondylitis and other Spondylarthropathies, except Psoriatic Arthritis<br>* Other names: Infliximab: 5 mg/kg / 6-8 weeks;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Rheumatology Society (SER) consensus, after one year | Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Society of Reumatology (SER) consensus (BASDAI < 4, global clinical impression by physician <4 and by patient < 4 and axial nocturnal pain <4) after one year | one year after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients in remission one year after inclusion in the study | Proportion of patients in remission, defined as ASDAS-C score lower than than 1.3, after one year from inclusion in the study | one year | 
| Proportion of patients who experience a clinical reactivation | Proportion of patients who experience a clinical reactivation, defined according criteria of active disease by Spanish Society of Reumatology (SER) consensus (BASDAI > 4, global clinical impression by physician >4 and at least one of three following criteria: patient impression >= 4, axial nocturnal pain (VAS) >= 4, and increased of acute phase reactants (reactive C protein (PCR) and/or erytrocyte sedimentation rate (ESR)) | last study visit (up to 3 years or December 2014) | 
| Proportion of patients who are kept in the acceptable therapeutic objective in the last study visit | Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Society of Reumatology (SER) consensus (BASDAI < 4, global clinical impression by physician <4 and by patient < 4 and axial nocturnal pain <4) in the last study visit | last study visit (up to 3 years or December 2014) | 
| Proportion of patients who are kept in the ideal therapeutic objective in the last follow visit | Proportion of patients who are kept in the ideal therapeutic objective according to the Spanish Society of Reumatology (SER) consensus (BASDAI < 2, global clinical impression by physician <2 and by patient < 2 ) in the last study visit | last study visit (up to 3 years or December 2014) | 
| Time to clinical reactivation | Time to clinical reactivation, defined according to the criteria of active disease by Spanish Society of Reumatology (SER) consensus, BASDAI + VAS and ASDAS, respectively | last study visit (up to 3 years or December 2014) | 
| Withdrawal because of clinical requirement to modify the antiTNF treatment. | Proportion of patients who are withdrawn from the study because of clinical requirement to modify the antiTNF treatment. | last study visit (up to 3 years or December 2014) | 
| NSAIDs use | NSAIDs use measured according semiquantitative Dougados criteria | last study visit (up to 3 years or December 2014) | 
| Suspected Serious Adverse Reactions | Proportion of patients who experience a Serious Adverse Event at least possibly related with anti-TNF therapy. | last study visit (up to 3 years or December 2014) | 
| Time to Suspected Serious Adverse Reaction | Time to Serious Adverse Events at least possibly related with anti-TNF therapy | last study visit (up to 3 years or December 2014) | 
| Proportion of patients in remission after two years from inclusion in the study | Proportion of patients in remission, defined as ASDAS-C point less than 1.3, after two years from inclusion in the study | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spondylarthropathies, Persistent clinical remission with anti-TNF therapy, Standardized protocol for dose reduction anti-TNF therapy