Clinical trial NCT00439283: Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis
Official title: Study of Two Schedules of Infliximab Maintenance Therapy in Ankylosing Spondylitis: Comparison of Infusion Every 6 Weeks Versus Infusion on Demand
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Keywords: Ankylosing spondylitis
infliximab
Systematic regimen
On-demand regimen
Lead sponsor: Association de Recherche Clinique en Rhumatologie
Sponsor class: OTHER
First posted: 2007-02-23
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: The primary end point was the proportion of patients with a 20% improvement response according to the ASAS criteria, at week 54.
Secondary outcomes:
measure: Achievement of the ASAS50 and ASAS70.
measure: The proportion of patients who experienced a partial remission, according to ASAS definition.
measure: Improvement in independent components of the ASAS response criteria.
measure: BASDAI.
measure: SF-36.
measure: Schober test.
measure: Finger to floor test.
measure: Chest expansion score.
measure: Occiput-to-wall measurements.
measure: Acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein level).
measure: Number of infusions administered after the loading regimen.
measure: Number of patients requiring an increase in the dose of infliximab.
measure: 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.
measure: 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.
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Besançon
country: France
facility: CHU Hôpital Minjoz
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Boulogne Billancourt
country: France
facility: Hôpital Ambroise Paré
city: Brest
country: France
facility: CHU de la Cavale Blanche
city: Caen
country: France
facility: CHU Côte de Nacre
city: Corbeil Essonnes
country: France
facility: Hôpital Gilles de Corbeil
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: Hôpital Général
city: Grenoble
country: France
facility: CHU A. Michallon
city: Le Havre
country: France
facility: Groupe Hospitalier du Havre
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lille
country: France
facility: CHRU Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU Dupuytren
city: Lomme
country: France
facility: Centre Hospitalier Saint Philibert
city: Lyon
country: France
facility: CH St Joseph - St Luc
city: Marseille
country: France
facility: Hôpital de la Conception
city: Montpellier
country: France
facility: Hôpital Lapeyronie
city: Nice
country: France
facility: CHU l'Archet 1
city: Orléans
country: France
facility: Hôpital Porte Madeleine
city: Paris
country: France
facility: Hôpital de la Pitié
city: Paris
country: France
facility: Hôpital Cochin
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU - Hôpital Sud
city: Rouen
country: France
facility: CHU - Hôpital de Bois Guillaume
city: Saint-Etienne
country: France
facility: CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Toulouse
country: France
facility: Hôpital de Purpan
city: Tours
country: France
facility: CHU Hôpital Trousseau
city: Vandoeuvre Les Nancy
country: France
facility: CHU Nancy-Brabois
Study officials:
affiliation: ARCR
name: Maxime DOUGADOS, Professor
role: STUDY_DIRECTOR
References:
citation: Fautrel B, Benhamou M, Breban M, Roy C, Lenoir C, Trape G, Baleydier A, Ravaud P, Dougados M. Cost effectiveness of two therapeutic regimens of infliximab in ankylosing spondylitis: economic evaluation within a randomised controlled trial. Ann Rheum Dis. 2010 Feb;69(2):424-7. doi: 10.1136/ard.2008.103887. Epub 2009 Sep 9.
citation: 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 Loet X, Wendling D, Fautrel B, Fournie 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. doi: 10.1002/art.23167.