Clinical trial NCT04360785: Effect of Two Methotrexate in Sync With the First Adalimumab to Prevent the Immunisation Anti Ada in Spondyloarthritis
Official title: Effect of Two Methotrexate Injections in Sync With the First Adalimumab Injection to Prevent the Immunisation Anti Adalimumab During Treatment of Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spondyloarthritis
Keywords: adalimumab
anti-drug antibodies
tolerization
methotrexate
spondyloarthritis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Preliminary report have demonstrated that methotrexate induces an anti bio-medicament tolerization whan administrated just before the first administration of the bio-medicament. Once this tolerization is obtained it seems useless to continue the methotrexate because this treatment has no efficacity in cases of spondyloarthritis.

Detailed description: spondyloarthritis are treated in first intention by NSAIDs but in case of inefficacity biotherapies that inhib the TNF are used. Adalimumab is the most used anti TNF in this indication. Monoclonal antibody uses in therapy is immunogene, and there is a clear link between increase of anti drug antibody and in one hand decrease of drug serum concentration and in an other failure of the therapeutic response. With adalimumab there is an apparition of ADAb in 30%. There are reports suggesting that adding methotrexate to the therapy in a specific timeline allow to prevent the immunization. A previous study shows that association in long terms between methotrexate and adalimumab induce less immunized patients. The investigator's goal is to assess if two methotrexate subcutaneous injections at day 1 and 2 could prevent anti adalimumab antibodies formation.

Eligibility criteria: Inclusion criteria :

* Patients aged from 18 to 90
* Patients suffering from axial SpA, radiographic or non-radiographic according to ASAS criteria (peripheral involvement and/or Inflammatory bowel diseases could be present).
* Indication for anti TNF treatment: resistance to at least 2 NSAIDs and no contraindication to adalimumab
* No previous treatment with methotrexate in the last 3 months
* Stable dosage of steroids (less than 10mg/day of prednisone equivalent) and/or of NSAIDs for at least 10 days
* Contraception feminine or masculine
* Informed and written consent
* Social insurance

Exclusion criteria :

* Contraindication to methotrexate
* Previous treatment with adalimumab
* Steroids more than 10mg/day of prednisone equivalent
* Previous treatment with:

  * Etanercept in the last month
  * Infliximab, golimumab, certolizumab in the last 2 months (Previous treatment hereafter these dates with anti-TNF except adalimumab or secukinumab are not a counterindication)
* Current immunosuppressive drugs except methotrexate
* Current and proven pregnancy
* Project of pregnancy in the next 3 months following inclusion
* Legal safeguards
* Inclusion in another interventional research project

Primary outcomes:
measure: serum concentrations of ADAb anti adalimumab
timeFrame: 6 month
Secondary outcomes:
measure: residual serum concentration of adalimumab
timeFrame: At 1, 3, 6 and 12 months
measure: serum concentrations of ADAb anti adalimumab
timeFrame: At 1, 3 and 12 months
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: At 1, 3, 6 and 12 months
measure: Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
timeFrame: At 3, 6 and 12 months
measure: Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
timeFrame: At 3, 6 and 12 months
measure: Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
timeFrame: At 3, 6 and 12 months
measure: Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
timeFrame: At 3, 6 and 12 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopital Pellegrin
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Paré
city: Brest
country: France
facility: Hopital La Cavale Blanche
city: Chambray-lès-Tours
country: France
facility: CHU Trousseau
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: Hopital Mondor
city: Le Kremlin-Bicêtre
country: France
facility: Kremlin Bicetre hospital
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: Hopital Saint Philibert
city: Nantes
country: France
facility: CHU Nantes
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Hopital Bichat
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital la Pitié Salpétrière
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pontoise
country: France
facility: CH Pontoise
city: Rouen
country: France
facility: CHU Rouen
Study officials:
affiliation: APHP
name: gaetane Nocturne
role: PRINCIPAL_INVESTIGATOR
References: