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

Purpose

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.

Condition	Intervention	Phase
Spondylarthropathies	Drug: Reduced doses of anti-TNF Drug: Stable doses of anti-TNF	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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.

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Spondylarthropathy

U.S. FDA Resources

Further study details as provided by Dra. Caridad Pontes, Spanish Clinical Pharmacology Society:

Primary Outcome Measures:

Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Rheumatology Society (SER) consensus, after one year [ Time Frame: one year after inclusion ]
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

Secondary Outcome Measures:

Proportion of patients in remission one year after inclusion in the study [ Time Frame: one year ]
Proportion of patients in remission, defined as ASDAS-C score lower than than 1.3, after one year from inclusion in the study
Proportion of patients who experience a clinical reactivation [ Time Frame: last study visit (up to 3 years or December 2014) ]
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))
Proportion of patients who are kept in the acceptable therapeutic objective in the last study visit [ Time Frame: last study visit (up to 3 years or December 2014) ]
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
Proportion of patients who are kept in the ideal therapeutic objective in the last follow visit [ Time Frame: last study visit (up to 3 years or December 2014) ]
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
Time to clinical reactivation [ Time Frame: last study visit (up to 3 years or December 2014) ]
Time to clinical reactivation, defined according to the criteria of active disease by Spanish Society of Reumatology (SER) consensus, BASDAI + VAS and ASDAS, respectively
Withdrawal because of clinical requirement to modify the antiTNF treatment. [ Time Frame: last study visit (up to 3 years or December 2014) ]
Proportion of patients who are withdrawn from the study because of clinical requirement to modify the antiTNF treatment.
NSAIDs use [ Time Frame: last study visit (up to 3 years or December 2014) ]
NSAIDs use measured according semiquantitative Dougados criteria
Suspected Serious Adverse Reactions [ Time Frame: last study visit (up to 3 years or December 2014) ]
Proportion of patients who experience a Serious Adverse Event at least possibly related with anti-TNF therapy.
Time to Suspected Serious Adverse Reaction [ Time Frame: last study visit (up to 3 years or December 2014) ]
Time to Serious Adverse Events at least possibly related with anti-TNF therapy
Proportion of patients in remission after two years from inclusion in the study [ Time Frame: 2 years ]
Proportion of patients in remission, defined as ASDAS-C point less than 1.3, after two years from inclusion in the study


Enrollment:	120
Study Start Date:	July 2012
Study Completion Date:	September 2015
Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Reduced doses of anti-TNF 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 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 Other Names: Adalimumab: 40 mg / 3 weeks Etanercept: 50 mg / 10 days Golimumab: 50 mg / 6 weeks Infliximab: 3 mg/kg / 8 weeks
Active Comparator: Stable doses of anti-TNF 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 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 Other Names: Adalimumab: 40 mg / 2 weeks Etanercept: 25 mg / 3 days ó 50 mg /7 days Golimumab: 50 mg / 4 weeks Infliximab: 5 mg/kg / 6-8 weeks

Arms

Assigned Interventions

Experimental: Reduced doses of anti-TNF

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

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

Other Names:

Adalimumab: 40 mg / 3 weeks
Etanercept: 50 mg / 10 days
Golimumab: 50 mg / 6 weeks
Infliximab: 3 mg/kg / 8 weeks

Active Comparator: Stable doses of anti-TNF

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

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

Other Names:

Adalimumab: 40 mg / 2 weeks
Etanercept: 25 mg / 3 days ó 50 mg /7 days
Golimumab: 50 mg / 4 weeks
Infliximab: 5 mg/kg / 6-8 weeks

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604629

Locations


Spain
Hospital Monte Naranco
Oviedo, Asturias, Spain
Hospital Universitario Central de Asturias
Oviedo, Asturias, Spain
Hospital General de Llerena-Zafra
Llerena, Badajoz, Spain
Hospital Universitario de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Corporació Sanitària Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital de Sant Joan Despí Moisès Broggi
Sant Joan Despí, Barcelona, Spain
Hospital Comarcal de Palamós
Palamós, Girona, Spain
Hospital Son Llàtzer
Palma de Mallorca, Illes Balears, Spain
Hospital Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria, Las Palmas, Spain
Hospital Universitario Príncipe de Asturias
Alcalá de Henares, Madrid, Spain
Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid, Spain
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain, 28222
Hospital Universitario de Móstoles
Móstoles, Madrid, Spain
Hospital Clínic Universitari Sant Joan d'Alacant
Alacant, Spain
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Hospital Vall d'Hebron
Barcelona, Spain
IMIM-Hospital del Mar
Barcelona, Spain
Hospital Reina Sofía
Córdoba, Spain
Hospital Universitario de Guadalajara
Guadalajara, Spain
Hospital Juan Canalejo
La Coruña, Spain
Hospital Clínico San Carlos
Madrid, Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario de La Princesa
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Universitario Virgen de la Arrixaca
Murcia, Spain
Hospital Clínico de Salamanca
Salamanca, Spain
Hospital Universitario Virgen Macarena
Sevilla, Spain
Hospital Sant Pau i Santa Tecla
Tarragona, Spain
Hospital General de Valencia
Valencia, Spain

Sponsors and Collaborators

Spanish Clinical Pharmacology Society

Spanish reumatology Society

Investigators


Principal Investigator:	Gratacós Jordi, MD, PhD	Hospital de Sabadell - Corporació Sanitària i Universitaria Parc Taulí UAB

More Information


Responsible Party:	Dra. Caridad Pontes, Study coordinator, Spanish Clinical Pharmacology Society
ClinicalTrials.gov Identifier:	NCT01604629 History of Changes
Other Study ID Numbers:	REDES-TNF/2012 2011-005871-18 ( EudraCT Number )
Study First Received:	May 17, 2012
Last Updated:	November 16, 2015

Keywords provided by Dra. Caridad Pontes, Spanish Clinical Pharmacology Society:


Spondylarthropathies Persistent clinical remission with anti-TNF therapy Standardized protocol for dose reduction anti-TNF therapy

Additional relevant MeSH terms:


Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases Bone Diseases Musculoskeletal Diseases Arthritis Joint Diseases Adalimumab Etanercept Infliximab Antibodies, Monoclonal	Anti-Inflammatory Agents Antirheumatic Agents Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Immunosuppressive Agents Immunologic Factors Dermatologic Agents

ClinicalTrials.gov processed this record on July 25, 2017

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