A Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Active Rheumatoid Arthritis (SERENE)

Genentech

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Methylprednisolone; Drug: Methotrexate; Drug: Folate; Drug: Placebo; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00299130

WA17045 (Other Identifier)

U2973g

Details and patient eligibility

About

This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).

Enrollment: 511 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients 18-80 years of age.

• Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.

• Receiving outpatient treatment for RA.

• Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.

• At screening, either

  • C-reactive protein (CRP) ≥ 0.6 mg/dL (6 mg/L), or
  • Erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour.

• Inadequate response to methotrexate, having received and tolerated at a dose of 10-25 mg/week it for ≥ 12 weeks.

Exclusion criteria

• Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA.
• Inflammatory joint disease other than RA, or other systemic autoimmune disorder.
• Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16.
• Surgery within 12 weeks of study or planned within 24 weeks of randomization.
• Previous treatment with any approved or investigational biological agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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511 participants in 3 patient groups

Placebo + methotrexate (MTX)

Active Comparator group

Description:

Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Treatment:

Drug: Folate

Drug: Rituximab

Drug: Placebo

Drug: Methotrexate

Drug: Methylprednisolone

Rituximab 2 x 0.5 g + MTX

Experimental group

Description:

Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Treatment:

Drug: Folate

Drug: Rituximab

Drug: Methotrexate

Drug: Methylprednisolone

Rituximab 2 x 1.0 g + MTX

Experimental group

Description:

Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Treatment:

Drug: Folate

Drug: Rituximab

Drug: Methotrexate

Drug: Methylprednisolone