A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate (SCORE)

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Methylprednisolone; Drug: Methotrexate; Drug: Folic acid or folate; Drug: Placebo; Biological: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00578305

MA21056

Details and patient eligibility

About

This 3 arm study assessed the efficacy of rituximab (MabThera®/Rituxan®) in the prevention of progression of structural joint damage in participants with active rheumatoid arthritis who had an inadequate clinical response to methotrexate. Participants were randomized to receive rituximab 500 mg intravenously (iv), rituximab 1000 mg iv, or placebo iv on days 1 and 15 every 24 weeks in the main study; all participants received concomitant methotrexate at a stable dose of 12.5-25 mg/week throughout the study. Further courses of rituximab were provided to eligible participants. Structural joint damage was assessed by magnetic resonance imaging (MRI) at baseline and at intervals during the study.

Full description

There were 3 phases in the study: A 52 week long main study, a study extension phase, and a 48 week long safety follow-up phase.

The first course of treatment with placebo or rituximab was initiated on Day 1 of the 52 week long main study. A second course of treatment was initiated after Week 24, if the participant met eligibility criteria. After Week 52, eligible participants received further treatment courses at intervals ≥ 6 months in the study extension phase. No treatments were administered in the safety follow-up phase.

Participants had to meet the following eligibility criteria to receive rituximab in the study extension phase.

• Minimum of 24 weeks had passed since the first infusion of the last course of study medication.

• C-reactive protein-based Disease Activity Score 28 (DAS28-CRP) ≥ 2.6.

• Absolute neutrophil count not below 1.5 x 103/μL.

• Patient had not developed contraindications for receiving rituximab, such as:

  1. Any new or uncontrolled concomitant disease such as, but not limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
  2. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
  3. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization, or treatment with iv anti-infectives within 4 weeks prior to infusion or completion of oral anti-infectives within 2 weeks prior to infusion.

• Patient was not pregnant or breast feeding.

• Patients who entered the study and were found to be hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (HBcAb) positive, were to be negative for hepatitis B viral DNA (< 29 IU/mL) and were to have aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) results within the last 12 weeks.

Enrollment: 185 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients, 18-80 years of age.
• Active rheumatoid arthritis for ≥ 3 months and ≤ 10 years.
• Evidence of erosive disease and/or clinical synovitis in a signal joint.
• Inadequate response to 12.5-25 mg/week methotrexate for ≥ 12 weeks.

Exclusion criteria

• Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis. - Any surgical procedure within 12 weeks prior to baseline.
• Previous treatment with a biologic agent or with a B cell modulating or cell depleting therapy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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185 participants in 3 patient groups, including a placebo group

Rituximab 500 mg

Experimental group

Description:

Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Treatment:

Biological: Rituximab

Drug: Methylprednisolone

Drug: Folic acid or folate

Drug: Methotrexate

Rituximab 1000 mg

Experimental group

Description:

Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Treatment:

Biological: Rituximab

Drug: Methylprednisolone

Drug: Folic acid or folate

Drug: Methotrexate

Placebo

Placebo Comparator group

Description:

Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Treatment:

Drug: Methylprednisolone

Drug: Folic acid or folate

Drug: Placebo

Drug: Methotrexate