A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: methotrexate; Drug: placebo; Drug: tocilizumab [RoActemra/Actemra]

Study type: Interventional

Funder types: Industry

Identifiers

NCT00810199

MA21488

2008-001847-20

Details and patient eligibility

About

This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.

Enrollment: 556 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult patients, ≥ 18 years of age;
• moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
• inadequate response to methotrexate;
• on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.

Exclusion criteria

• prior treatment with a biologic;
• Rheumatoid arthritis (RA) functional class IV;
• known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
• evidence of active malignant disease.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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556 participants in 2 patient groups, including a placebo group

Tocilizumab + Methotrexate

Experimental group

Description:

Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: methotrexate

Tocilizumab + Placebo

Placebo Comparator group

Description:

Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.

Treatment:

Drug: placebo

Drug: tocilizumab [RoActemra/Actemra]