Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis

Phase 3

Completed

• Conditions: Ankylosing Spondylitis

• Registration Number: NCT00439283
• Lead Sponsor: Association de Recherche Clinique en Rhumatologie

Brief Summary

Continuous treatment with the anti-tumor necrosis factor alpha monoclonal antibody infliximab is efficacious in ankylosing spondylitis (AS), whereas treatment discontinuation results in disease relapse, with variable delay. Objective of this study was to compare efficacy between a continuous treatment with infliximab, and a treatment adapted to symptoms recurrence. Addition of methotrexate (MTX)to infliximab was also tested.

Detailed Description

Patients with active AS were randomly assigned to receive infliximab every 6 weeks (Q6), or only upon symptoms recurrence (on-demand), following a loading regimen of infusions at weeks 0, 2, and 6. Patients in the latter group were randomly assigned to receive MTX or not, starting 4 weeks prior to infliximab. Monitoring was performed over one year. The primary end point was the proportion of patients with a 20% improvement response according to the ASsessment in Ankylosing Spondylitis (ASAS) criteria, at week 54.

Study Timeline

• Study Start: 2003-04
• Study Completion: 2004-12
• Status Verified: 2007-02
• Study First Submitted: 2007-02-22
• Study First Submitted QC: 2007-02-22
• Study First Posted: 2007-02-23
• Last Update Submitted: 2007-02-26
• Last Update Posted: 2007-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Adult patients (> 18 years old)
• With a diagnosis of AS
• With at least one of the following evidences for active inflammation, present within 3 months before inclusion: a serum C-reactive protein (CRP) level above twice the upper limit value of the normal range, a positive magnetic resonance imaging of the spine or sacro-iliac joints, a vascularized enthesitis by power-Doppler ultrasound technic.
• Presence of clinically active axial disease, as defined by 1) a Bath AS Disease Activity Index (BASDAI) (18) of ≥ 3/10, and 2) a score of ≥ 3/10 for axial pain (second item of BASDAI).
• Disease-modifying antirheumatic drugs (DMARDs), such as sulphasalazine, methotrexate, hydroxychloroquine, intra-muscular gold, thiol compound, cyclosporin, intravenous biphosphonate had to be discontinued for at least 4 weeks before inclusion.
• Dosages of NSAIDs and corticosteroid were required to remain stable for at least 4 weeks before inclusion.
• A negative pregnancy test result was required for non menopausal female patients, and contraception during the study period and for six months after the last infusion of infliximab was recommended to all patients of childbearing potential.

Exclusion Criteria

• Pregnancy.
• Breastfeeding.
• Vaccination with a live organism during the last month.
• Present infection or any episode of serious infection within the last three months.
• Active malignancy within the previous five years.
• Alcohol or drug addiction.
• Severe chronic concomitant disease.
• Administration of an investigational drug within the last three months, or of any known TNF inhibitor therapy in the past (such as thalidomide, infliximab or etanercept).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary end point was the proportion of patients with a 20% improvement response according to the ASAS criteria, at week 54.

Secondary Outcome Measures

Name	Time	Method
Achievement of the ASAS50 and ASAS70.
The proportion of patients who experienced a partial remission, according to ASAS definition.
Improvement in independent components of the ASAS response criteria.
BASDAI.
SF-36.
Schober test.
Finger to floor test.
Chest expansion score.
Occiput-to-wall measurements.
Acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein level).
Number of infusions administered after the loading regimen.
Number of patients requiring an increase in the dose of infliximab.
The area under the curves (AUCs) of the BASDAI recorded on a weekly basis on automatic phone server, calculated from week 0 through week 54.
The area under the curves (AUCs) of the global pain scores recorded on a weekly basis on automatic phone server, calculated from week 0 through week 54.

Trial Locations

Locations (31)

CHU Amiens; 🇫🇷 Amiens, France

CHU Hôpital Minjoz; 🇫🇷 Besançon, France

Hôpital Gilles de Corbeil; 🇫🇷 Corbeil Essonnes, France

CHRU Hôpital Roger Salengro; 🇫🇷 Lille, France

CHU Dupuytren; 🇫🇷 Limoges, France

Hôpital Ambroise Paré; 🇫🇷 Boulogne Billancourt, France

Centre Hospitalier Saint Philibert; 🇫🇷 Lomme, France

CHU - Hôpital de Bois Guillaume; 🇫🇷 Rouen, France

CHU de la Cavale Blanche; 🇫🇷 Brest, France

CHU Côte de Nacre; 🇫🇷 Caen, France

Hôpital Bicêtre; 🇫🇷 Le Kremlin Bicêtre, France

Hôpital Lapeyronie; 🇫🇷 Montpellier, France

Hôpital Général; 🇫🇷 Dijon, France

Hôpital de la Conception; 🇫🇷 Marseille, France

Hôpital Porte Madeleine; 🇫🇷 Orléans, France

CHU Nancy-Brabois; 🇫🇷 Vandoeuvre Les Nancy, France

Hôpital de Purpan; 🇫🇷 Toulouse, France

CH St Joseph - St Luc; 🇫🇷 Lyon, France

Hôpital Cochin; 🇫🇷 Paris, France

CHU - Hôpital Sud; 🇫🇷 Rennes, France

CHU Saint-Etienne; 🇫🇷 Saint-Etienne, France

CHU Hautepierre; 🇫🇷 Strasbourg, France

CHU Hôpital Trousseau; 🇫🇷 Tours, France

Hôpital Avicenne; 🇫🇷 Bobigny, France

Hôpital Pellegrin; 🇫🇷 Bordeaux, France

CHU A. Michallon; 🇫🇷 Grenoble, France

Hôpital Henri Mondor; 🇫🇷 Creteil, France

Groupe Hospitalier du Havre; 🇫🇷 Le Havre, France

Hôpital de la Pitié; 🇫🇷 Paris, France

CHU l'Archet 1; 🇫🇷 Nice, France

CHU de Poitiers; 🇫🇷 Poitiers, France