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

Spondyloarthritis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04360785
• Other study ID #: APHP180571
• Status: Completed
• Phase: N/A
• Start date: November 11, 2020
• Est. completion date: February 27, 2023

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: February 27, 2023
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Spondylarthritis
• Spondylitis
• Spondyloarthritis

Intervention

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

Locations

Country	Name	City	State
France	Hopital Pellegrin	Bordeaux
France	Hopital Ambroise Paré	Boulogne-Billancourt
France	Hopital La Cavale Blanche	Brest
France	CHU Trousseau	Chambray-lès-Tours
France	CH Sud Francilien	Corbeil-Essonnes
France	Hopital Mondor	Créteil
France	Kremlin Bicetre hospital	Le Kremlin-Bicêtre
France	CH Le Mans	Le Mans
France	Hopital Saint Philibert	Lille
France	CHU Nantes	Nantes
France	CHR Orléans	Orléans
France	Hopital Bichat	Paris
France	Hopital Cochin	Paris
France	Hopital la Pitié Salpétrière	Paris
France	Hopital Saint Antoine	Paris
France	CH Pontoise	Pontoise
France	CHU Rouen	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 month
Secondary	residual serum concentration of adalimumab	To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.	At 1, 3, 6 and 12 months
Secondary	serum concentrations of ADAb anti adalimumab	To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups	At 1, 3 and 12 months
Secondary	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	At 1, 3, 6 and 12 months
Secondary	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)	At 3, 6 and 12 months
Secondary	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)	At 3, 6 and 12 months
Secondary	Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance	Assess by Number of patient who didn't switch treatment	At 3, 6 and 12 months
Secondary	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)	At 3, 6 and 12 months