Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide

Rheumatoid Arthritis Clinical Trial

— BIO3  

Official title:

Randomized Controlled Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02714634
• Other study ID #: 6020
• Status: Recruiting
• Phase: Phase 4
• Start date: March 30, 2016
• Est. completion date: March 2025

Study information

• Verified date: July 2022
• Source: University Hospital, Strasbourg, France
• Contact: Jacques-Eric GOTTENBERG, Professor
• Phone: 3 88 12 79 53
• Email: jacques-eric.gottenberg[@]chru-strasbourg.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 286
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria

• DAS28-CRP>3.2

• Insufficient response to methotrexate at a weekly dose=15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment

• RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)

• Age greater or equal to 18 years

• Written informed consent, dated and signed before initiating any trial-related procedure

• Affiliation to a social insurance system

• Women of child bearing potential, negative ß-HCG assay (Human chorionic gonadotropin)

• Effective method of birth control during the study and continuing after the discontinuation of the investigational drug or study. The duration will depend on the drug used (referred to the summary product characteristic).

Exclusion Criteria:

• Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)

• Previous treatment with triple therapy

• Other inflammatory arthritis except RA associated with Sjögren's syndrome

• Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine

• Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion

• Absence of tuberculosis screening

• Patient who cannot be followed during 12 months

• Pregnancy, breastfeeding, desire of pregnancy in the 12 months

• Drug addiction, addiction to alcohol

• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment

• Women of child bearing potential, unless they are using an effective method of birth control

• Patient under law protection

• Prisoners

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate + targeted therapy administration
Methotrexate or leflunomide + adalimumab or Methotrexate or leflunomide + certolizumab or Methotrexate or leflunomide + etanercept or Methotrexate or leflunomide + golimumab or Methotrexate or leflunomide + infliximab or Methotrexate or leflunomide + abatacept or Methotrexate or leflunomide + rituximab or Methotrexate or leflunomide + tocilizumab or Methotrexate or leflunomide + sarilumab or Methotrexate or leflunomide + filgotinib or Methotrexate or leflunomide + upadacitinib or Methotrexate or leflunomide + Tofacitinib or Methotrexate or leflunomide + baricitinib
• methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration

Locations

Country	Name	City	State
France	Hôpitaux Universitaires de Strasbourg	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose = 7.5 mg/day of equivalent prednisone		At 12 months
Secondary	Serious adverse events rate		At 3, 6, 9 and at 12 months
Secondary	Blood concentrations of hydroxychloroquine, leflunomide, sulfasalazine and methotrexate in the triple therapy group and methotrexate, leflunomide, biologic / JAK/STAT inhibitor and anti-drug antibody in the other group.		at 6, and 12 months
Secondary	Clinical disease activity index (CDAI).		At inclusion, 3, 6, 9 and 12 months
Secondary	DAS 28 CRP score.		at inclusion, 3, 6, 9 and 12 months.
Secondary	2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission.		at 3, 6, 9 and 12 months.
Secondary	Modified Sharp Van der Heijde score.		at inclusion and at 12 months
Secondary	Change in comedications (dose)		at 3, 6, 9 and 12 months
Secondary	Change in comedications (route of administration)		at 3, 6, 9 and 12 months
Secondary	Change in comedications (drug)		at 3, 6, 9 and 12 months
Secondary	QUALISEX score at inclusion, 6 months and at 12 months.		at inclusion, 6 months and at 12 months.
Secondary	Medico-economic costs.		at inclusion, 3, 6, 9 and at 12 months.
Secondary	Treatment compliance	A questionnaire will be filled by patient	at 3, 6, 9 and 12 months