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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04360785

Collaborator

(none)

124

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Spondyloarthritis	Drug: Methotrexate	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

serum concentrations of ADAb anti adalimumab [6 month]
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 [At 1, 3, 6 and 12 months]
To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.
serum concentrations of ADAb anti adalimumab [At 1, 3 and 12 months]
To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups
Incidence of Treatment-Emergent Adverse Events [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
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS score. [At 3, 6 and 12 months]
A therapeutic efficacity will be described as a clinical pertinent increase of ASDAS : Ankylosing Spondylitis Disease Activity Score (at least 1,1 point)
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI score. [At 3, 6 and 12 months]
A therapeutic efficacity will be described as a clinical pertinent increase of BASDAI : Bath Ankylosing Spondylitis Disease Activity Index (at least 2 points)
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance [At 3, 6 and 12 months]
Assess by Number of patient who didn't switch treatment
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction [At 3, 6 and 12 months]
Assess by ASAS-NSAIDS score (Assessment of SpondyloArthritis international Society - nonsteroidal antiinflammatory drugs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts 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