Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis

Ankylosing Spondylitis Clinical Trial

Official title:

Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis: Comparison of Infusion Every 6 Weeks Versus Infusion on Demand

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00439283
• Other study ID #: A R C R 2003 - 01 / PO 3353
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2007
• Last updated: February 26, 2007
• Start date: April 2003
• Est. completion date: December 2004

Study information

• Verified date: February 2007
• Source: Association de Recherche Clinique en Rhumatologie
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• infliximab

• methotrexate

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU Hôpital Minjoz	Besançon
France	Hôpital Avicenne	Bobigny
France	Hôpital Pellegrin	Bordeaux
France	Hôpital Ambroise Paré	Boulogne Billancourt
France	CHU de la Cavale Blanche	Brest
France	CHU Côte de Nacre	Caen
France	Hôpital Gilles de Corbeil	Corbeil Essonnes
France	Hôpital Henri Mondor	Creteil
France	Hôpital Général	Dijon
France	CHU A. Michallon	Grenoble
France	Groupe Hospitalier du Havre	Le Havre
France	Hôpital Bicêtre	Le Kremlin Bicêtre
France	CHRU Hôpital Roger Salengro	Lille
France	CHU Dupuytren	Limoges
France	Centre Hospitalier Saint Philibert	Lomme
France	CH St Joseph - St Luc	Lyon
France	Hôpital de la Conception	Marseille
France	Hôpital Lapeyronie	Montpellier
France	CHU l'Archet 1	Nice
France	Hôpital Porte Madeleine	Orléans
France	Hôpital Cochin	Paris
France	Hôpital de la Pitié	Paris
France	CHU de Poitiers	Poitiers
France	CHU - Hôpital Sud	Rennes
France	CHU - Hôpital de Bois Guillaume	Rouen
France	CHU Saint-Etienne	Saint-Etienne
France	CHU Hautepierre	Strasbourg
France	Hôpital de Purpan	Toulouse
France	CHU Hôpital Trousseau	Tours
France	CHU Nancy-Brabois	Vandoeuvre Les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Association de Recherche Clinique en Rhumatologie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point was the proportion of patients with a 20% improvement response according to the ASAS criteria, at week 54.
Secondary	Achievement of the ASAS50 and ASAS70.
Secondary	The proportion of patients who experienced a partial remission, according to ASAS definition.
Secondary	Improvement in independent components of the ASAS response criteria.
Secondary	BASDAI.
Secondary	SF-36.
Secondary	Schober test.
Secondary	Finger to floor test.
Secondary	Chest expansion score.
Secondary	Occiput-to-wall measurements.
Secondary	Acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein level).
Secondary	Number of infusions administered after the loading regimen.
Secondary	Number of patients requiring an increase in the dose of infliximab.
Secondary	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.
Secondary	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.