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

October 2, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Effect of Two Methotrexate Injections in Sync With the First Adalimumab Injection to Prevent the Immunisation Anti Adalimumab During Treatment of Spondyloarthritis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France
        • Hôpital Pellegrin
      • Boulogne-Billancourt, France
        • Hopital Ambroise Pare
      • Brest, France
        • Hopital La Cavale Blanche
      • Chambray-lès-Tours, France
        • CHU Trousseau
      • Corbeil-Essonnes, France
        • CH SUd Francilien
      • Créteil, France
        • Hôpital Mondor
      • Le Kremlin-Bicêtre, France
        • Kremlin Bicetre hospital
      • Le Mans, France
        • CH Le Mans
      • Lille, France
        • Hôpital Saint Philibert
      • Nantes, France
        • CHU Nantes
      • Orléans, France
        • CHR Orléans
      • Paris, France
        • Hôpital Bichat
      • Paris, France
        • Hopital Saint Antoine
      • Paris, France
        • Hopital Cochin
      • Paris, France
        • Hôpital La Pitié Salpêtrière
      • Pontoise, France
        • CH Pontoise
      • Rouen, France
        • CHU Rouen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methotrexate + Adalimumab
Experimental group : patients will receive 2 subcutaneous injections of methotrexate in addition of the usual adalimumab
Drug: Methotrexate
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
No Intervention: Adalimumab
Reference group : patient will receive adalimumab as usual to treat spondyloarthritis

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
residual serum concentration of adalimumab
Time Frame: At 1, 3, 6 and 12 months
To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.
At 1, 3, 6 and 12 months
serum concentrations of ADAb anti adalimumab
Time Frame: At 1, 3 and 12 months
To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups
At 1, 3 and 12 months
Incidence of Treatment-Emergent Adverse Events
Time Frame: At 1, 3, 6 and 12 months
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
At 1, 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
Time Frame: At 3, 6 and 12 months
Assess by Number of patient who didn't switch treatment
At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
Time Frame: At 3, 6 and 12 months
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)
At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
Time Frame: At 3, 6 and 12 months
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)
At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
Time Frame: At 3, 6 and 12 months
Assess by ASAS-NSAIDS score (Assessment of SpondyloArthritis international Society - nonsteroidal antiinflammatory drugs) (minimum 0. a higher score means a worse outcome)
At 3, 6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: gaetane Nocturne, APHP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2020

Primary Completion (Actual)

September 13, 2022

Study Completion (Actual)

February 27, 2023

Study Registration Dates

First Submitted

March 2, 2020

First Submitted That Met QC Criteria

April 21, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

October 4, 2023

Last Update Submitted That Met QC Criteria

October 2, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP180571

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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