Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis - Full Text View

Sponsored by:	Association de Recherche Clinique en Rhumatologie
Information provided by:	Association de Recherche Clinique en Rhumatologie
ClinicalTrials.gov Identifier:	NCT00439283

Purpose

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.

Condition	Intervention	Phase
Ankylosing Spondylitis	Drug: infliximab Drug: methotrexate	Phase III

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis

Drug Information available for: Methotrexate Infliximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study
Official Title:	Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis: Comparison of Infusion Every 6 Weeks Versus Infusion on Demand

Further study details as provided by Association de Recherche Clinique en Rhumatologie:

Primary Outcome Measures:

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:

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.

Estimated Enrollment:	240
Study Start Date:	April 2003
Estimated Study Completion Date:	December 2004

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439283

Locations

France
Hôpital Cochin
Paris, France, 75014
Hôpital Ambroise Paré
Boulogne Billancourt, France, 92104
Hôpital Henri Mondor
CRETEIL, France, 94010
CHRU Hôpital Roger Salengro
LILLE, France, 59037
CHU Amiens
Amiens, France, 80054
CHU - Hôpital de Bois Guillaume
Rouen, France, 76031
CHU de la Cavale Blanche
Brest, France, 29609
CHU - Hôpital Sud
Rennes, France, 35056
Centre Hospitalier Saint Philibert
LOMME, France, 59160
Hôpital Porte Madeleine
Orléans, France, 45032
CHU Hautepierre
Strasbourg, France, 67098
Hôpital Avicenne
Bobigny, France, 93009
Hôpital Pellegrin
Bordeaux, France, 33076
Hôpital de Purpan
Toulouse, France, 31059
CHU l'Archet 1
Nice, France, 06202
Hôpital Lapeyronie
Montpellier, France, 34295
Hôpital Lapeyronie
Montpellier, France, 34295
CHU Côte de Nacre
Caen, France, 14033
CHU Hôpital Minjoz
Besançon, France, 25030
CHU Dupuytren
Limoges, France, 87042
CHU Hôpital Trousseau
Tours, France, 37044
Hôpital Général
Dijon, France, 21000
CHU Saint-Etienne
Saint-Etienne, France, 42055
Hôpital Bicêtre
Le Kremlin Bicêtre, France, 94275
Hôpital de la Pitié
Paris, France, 75013
CHU Nancy-Brabois
Vandoeuvre Les Nancy, France, 54511
Hôpital de la Conception
Marseille, France, 13385
Hôpital Gilles de Corbeil
Corbeil Essonnes, France, 91106
Groupe Hospitalier du Havre
Le Havre, France, 76083
CHU de Poitiers
Poitiers, France, 86021
CH St Joseph - St Luc
Lyon, France, 69365
CHU A. Michallon
Grenoble, France, 38043

Sponsors and Collaborators

Association de Recherche Clinique en Rhumatologie

Investigators

Study Director:

Maxime DOUGADOS, Professor

ARCR

More Information

Publications indexed to this study:

Breban M, Ravaud P, Claudepierre P, Baron G, Henry YD, Hudry C, Euller-Ziegler L, Pham T, Solau-Gervais E, Chary-Valckenaere I, Marcelli C, Perdriger A, Le Loët X, Wendling D, Fautrel B, Fournié B, Combe B, Gaudin P, Jousse S, Mariette X, Baleydier A, Trape G, Dougados M; French Ankylosing Spondylitis Infliximab Network. Maintenance of infliximab treatment in ankylosing spondylitis: results of a one-year randomized controlled trial comparing systematic versus on-demand treatment. Arthritis Rheum. 2008 Jan;58(1):88-97.

Study ID Numbers:	A R C R 2003 - 01 / PO 3353
Study First Received:	February 22, 2007
Last Updated:	February 26, 2007
ClinicalTrials.gov Identifier:	NCT00439283
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Association de Recherche Clinique en Rhumatologie:

Ankylosing spondylitis
infliximab
Systematic regimen
On-demand regimen

Study placed in the following topic categories:

Spinal Diseases
Infliximab
Joint Diseases
Spondylarthropathy
Bone Diseases
Folic Acid
Musculoskeletal Diseases

Arthritis
Spondylitis, Ankylosing
Methotrexate
Spondylarthritis
Spondylitis
Spondylarthropathies
Ankylosis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Enzyme Inhibitors
Reproductive Control Agents
Folic Acid Antagonists

Infection
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Bone Diseases, Infectious
Therapeutic Uses
Abortifacient Agents
Antirheumatic Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009