Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.

P. Verschueren

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Sulfasalazine; Drug: Prednisone; Drug: Leflunomide; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT01172639

2008-007225-39 (EudraCT Number)

CareRA

Details and patient eligibility

About

The Combinatietherapie Bij Reumatoide Artritis (CoBRA) trial was a milestone in the development of the present treatment paradigm for Rheumatoid Arthritis (RA). This study introduced the principle of fast remission induction by means of a combination of standard Disease Modifying AntiRheumatic Drugs (DMARDs) and a step down bridge therapy with high dose glucocorticoids in early Rheumatoid Arthritis.

The purpose of the present study is to compare different combinations of traditional DMARDs and glucocorticoids, based on the original CoBRA protocol, for treatment of early Rheumatoid Arthritis.

Besides the efficacy and effectiveness of these strategies, patient centered outcomes and potential implementation problems of such treatment strategies are evaluated.

Enrollment: 400 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of RA as defined by the 1987 or 2010 revised American College of Rheumatology (ACR) criteria
• Early RA (less than 1 year)
• Use a reliable method of contraception for women of childbearing potential
• Able and willing to give written informed consent and participate in the study

Exclusion criteria

• Previous treatment with DMARDs
• Previous treatment with oral corticosteroids at a dosage of more than 10 milligrams (mg) prednisone within 4 weeks before baseline
• Previous treatment with oral corticosteroids at a dosage equal to or less than 10 mg prednisone within 2 weeks before baseline
• Previous treatment with oral corticosteroids for more than 4 weeks
• Previous treatment with Intra Articular corticosteroids within 4 weeks before baseline
• Previous treatment with an investigational drug for the treatment or prevention of RA
• Contraindications for corticosteroids
• Contraindications for DMARDs
• Psoriatic Arthritis
• Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
• Pregnancy, breastfeeding or no use of a reliable method of contraception
• Alcohol or drug abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 5 patient groups

CoBRA classic high risk group

Other group

Description:

* Methotrexate 15mg tablet by mouth, weekly for entire trial * Sulfasalazine 2g tablet by mouth, daily for 40 weeks * Prednisone tablet by mouth, weekly step down scheme 60 - 40 - 25 - 20 - 15 - 10 mg daily for 6 weeks, followed by 7.5mg daily till week 28, then further tapered down to stop at week 32

Treatment:

Drug: Methotrexate

Drug: Prednisone

Drug: Sulfasalazine

CoBRA slim high risk group

Other group

Description:

* Methotrexate 15mg tablet by mouth, weekly for entire trial * Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32

Treatment:

Drug: Methotrexate

Drug: Prednisone

CoBRA avant-garde high risk group

Other group

Description:

* Methotrexate 15mg tablet by mouth, weekly for 40 weeks (continued for entire trial if randomized to Methotrexate monotherapy at week 40) * Leflunomide 10mg tablet by mouth, daily for 40 weeks (continued for entire trial if randomized to Leflunomide monotherapy at week 40) * Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32

Treatment:

Drug: Methotrexate

Drug: Prednisone

Drug: Leflunomide

CoBRA slim low risk group

Other group

Description:

* Methotrexate 15mg tablet by mouth, weekly for entire trial * Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32

Treatment:

Drug: Methotrexate

Drug: Prednisone

Tight Step Up low risk group

Other group

Description:

* Methotrexate 15mg tablet by mouth, weekly for entire trial * No oral steroids allowed during the first year of the trial

Treatment:

Drug: Methotrexate