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Effect of Two Methotrexate in Sync With the First Adalimumab to Prevent the Immunisation Anti Ada in Spondyloarthritis (MESYNAD)

Primary Purpose

Spondyloarthritis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Methotrexate
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Spondyloarthritis focused on measuring adalimumab, anti-drug antibodies, tolerization, methotrexate, spondyloarthritis

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Pellegrin
  • Hopital Ambroise Paré
  • Hopital La Cavale Blanche
  • CHU Trousseau
  • CH Sud Francilien
  • Hopital Mondor
  • Kremlin Bicetre hospital
  • CH Le Mans
  • Hopital Saint Philibert
  • CHU Nantes
  • CHR Orléans
  • Hopital Bichat
  • Hopital Cochin
  • Hopital la Pitié Salpétrière
  • Hopital Saint Antoine
  • CH Pontoise
  • CHU Rouen

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Methotrexate + Adalimumab

Adalimumab

Arm Description

Experimental group : patients will receive 2 subcutaneous injections of methotrexate in addition of the usual adalimumab

Reference group : patient will receive adalimumab as usual to treat spondyloarthritis

Outcomes

Primary Outcome Measures

serum concentrations of ADAb anti adalimumab
To assess if 2 subcutaneous injections of methotrexate could prevent anti adalimumab antibodies formation at month 6 in patients with spondyloarthritis

Secondary Outcome Measures

residual serum concentration of adalimumab
To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.
serum concentrations of ADAb anti adalimumab
To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events as assessed by the number of AE and SAE related to the treatment that occur during the participation of the patient
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
A therapeutic efficacity will be described as a clinical pertinent change of ASDAS : Ankylosing Spondylitis Disease Activity Score (at least 1,1 point) (a higher score means a worse outcome)
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
A therapeutic efficacity will be described as a clinical pertinent change of BASDAI : Bath Ankylosing Spondylitis Disease Activity Index (0 to 50 points - a higher score means a worse outcome)
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
Assess by Number of patient who didn't switch treatment
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
Assess by ASAS-NSAIDS score (Assessment of SpondyloArthritis international Society - nonsteroidal antiinflammatory drugs) (minimum 0. a higher score means a worse outcome)

Full Information

First Posted
March 2, 2020
Last Updated
October 2, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04360785
Brief Title
Effect of Two Methotrexate in Sync With the First Adalimumab to Prevent the Immunisation Anti Ada in Spondyloarthritis
Acronym
MESYNAD
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
November 11, 2020 (Actual)
Primary Completion Date
September 13, 2022 (Actual)
Study Completion Date
February 27, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spondyloarthritis
Keywords
adalimumab, anti-drug antibodies, tolerization, methotrexate, spondyloarthritis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methotrexate + Adalimumab
Arm Type
Experimental
Arm Description
Experimental group : patients will receive 2 subcutaneous injections of methotrexate in addition of the usual adalimumab
Arm Title
Adalimumab
Arm Type
No Intervention
Arm Description
Reference group : patient will receive adalimumab as usual to treat spondyloarthritis
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Patients randomized in this arm will have one subcutaneous injection of methotrexate 15min before and one 24h after their first injection of adalimumab prescribed as usual
Primary Outcome Measure Information:
Title
serum concentrations of ADAb anti adalimumab
Description
To assess if 2 subcutaneous injections of methotrexate could prevent anti adalimumab antibodies formation at month 6 in patients with spondyloarthritis
Time Frame
6 month
Secondary Outcome Measure Information:
Title
residual serum concentration of adalimumab
Description
To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.
Time Frame
At 1, 3, 6 and 12 months
Title
serum concentrations of ADAb anti adalimumab
Description
To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups
Time Frame
At 1, 3 and 12 months
Title
Incidence of Treatment-Emergent Adverse Events
Description
Incidence of Treatment-Emergent Adverse Events as assessed by the number of AE and SAE related to the treatment that occur during the participation of the patient
Time Frame
At 1, 3, 6 and 12 months
Title
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
Description
A therapeutic efficacity will be described as a clinical pertinent change of ASDAS : Ankylosing Spondylitis Disease Activity Score (at least 1,1 point) (a higher score means a worse outcome)
Time Frame
At 3, 6 and 12 months
Title
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
Description
A therapeutic efficacity will be described as a clinical pertinent change of BASDAI : Bath Ankylosing Spondylitis Disease Activity Index (0 to 50 points - a higher score means a worse outcome)
Time Frame
At 3, 6 and 12 months
Title
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
Description
Assess by Number of patient who didn't switch treatment
Time Frame
At 3, 6 and 12 months
Title
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
Description
Assess by ASAS-NSAIDS score (Assessment of SpondyloArthritis international Society - nonsteroidal antiinflammatory drugs) (minimum 0. a higher score means a worse outcome)
Time Frame
At 3, 6 and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
gaetane Nocturne
Organizational Affiliation
APHP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Pellegrin
City
Bordeaux
Country
France
Facility Name
Hopital Ambroise Paré
City
Boulogne-Billancourt
Country
France
Facility Name
Hopital La Cavale Blanche
City
Brest
Country
France
Facility Name
CHU Trousseau
City
Chambray-lès-Tours
Country
France
Facility Name
CH Sud Francilien
City
Corbeil-Essonnes
Country
France
Facility Name
Hopital Mondor
City
Créteil
Country
France
Facility Name
Kremlin Bicetre hospital
City
Le Kremlin-Bicêtre
Country
France
Facility Name
CH Le Mans
City
Le Mans
Country
France
Facility Name
Hopital Saint Philibert
City
Lille
Country
France
Facility Name
CHU Nantes
City
Nantes
Country
France
Facility Name
CHR Orléans
City
Orléans
Country
France
Facility Name
Hopital Bichat
City
Paris
Country
France
Facility Name
Hopital Cochin
City
Paris
Country
France
Facility Name
Hopital la Pitié Salpétrière
City
Paris
Country
France
Facility Name
Hopital Saint Antoine
City
Paris
Country
France
Facility Name
CH Pontoise
City
Pontoise
Country
France
Facility Name
CHU Rouen
City
Rouen
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effect of Two Methotrexate in Sync With the First Adalimumab to Prevent the Immunisation Anti Ada in Spondyloarthritis

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