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

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.

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.

Study Overview

• Status: Completed
• Conditions: Spondylarthropathies
• Intervention / Treatment: Drug: Reduced doses of anti-TNF; Drug: Stable doses of anti-TNF

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alacant, Spain
    • Hospital Clínic Universitari Sant Joan d'Alacant
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • IMIM-Hospital del Mar
  • Córdoba, Spain
    • Hospital Reina Sofia
  • Guadalajara, Spain
    • Hospital Universitario de Guadalajara
  • La Coruña, Spain
    • Hospital Juan Canalejo
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario de la Princesa
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Murcia, Spain
    • Hospital Universitario Virgen de la Arrixaca
  • Salamanca, Spain
    • Hospital Clínico de Salamanca
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Tarragona, Spain
    • Hospital Sant Pau i Santa Tecla
  • Valencia, Spain
    • Hospital General de Valencia
  • Asturias
    • Oviedo, Asturias, Spain
      • Hospital Universitario Central de Asturias
    • Oviedo, Asturias, Spain
      • Hospital Monte Naranco
  • Badajoz
    • Llerena, Badajoz, Spain
      • Hospital General de Llerena-Zafra
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
    • Sant Joan Despí, Barcelona, Spain
      • Hospital de Sant Joan Despi Moises Broggi
  • Girona
    • Palamós, Girona, Spain
      • Hospital Comarcal de Palamós
  • Illes Balears
    • Palma de Mallorca, Illes Balears, Spain
      • Hospital Son Llatzer
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain
      • Hospital Universitario de Gran Canaria Dr. Negrin
  • Madrid
    • Alcalá de Henares, Madrid, Spain
      • Hospital Universitario Príncipe de Asturias
    • Alcorcón, Madrid, Spain
      • Hospital Universitario Fundacion Alcorcon
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
    • Móstoles, Madrid, Spain
      • Hospital Universitario de Móstoles

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spanish Clinical Pharmacology Society
• Collaborators: Spanish reumatology Society
• Investigators: Principal Investigator: Gratacós Jordi, MD, PhD, Hospital de Sabadell - Corporació Sanitària i Universitaria Parc Taulí UAB

Publications and helpful links

General Publications

• Gratacos J, Pontes C, Juanola X, Sanz J, Torres F, Avendano C, Vallano A, Calvo G, de Miguel E, Sanmarti R; REDES-TNF investigators. Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Ther. 2019 Jan 8;21(1):11. doi: 10.1186/s13075-018-1772-z.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 24, 2012

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Spondylarthropathies; Persistent clinical remission with anti-TNF therapy; Standardized protocol for dose reduction anti-TNF therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthritis; Spondylitis; Spondylarthropathies; 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; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Etanercept; Adalimumab; Antibodies, Monoclonal; Infliximab; Golimumab
• Other Study ID Numbers: REDES-TNF/2012; 2011-005871-18 (EudraCT Number)