Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis (PREMIER)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Early Rheumatoid Arthritis

Treatments: Drug: Methotrexate placebo; Biological: Adalimumab; Biological: Adalimumab placebo; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00195663

DE013

Details and patient eligibility

About

The purpose of the study is to assess the safety and efficacy of adalimumab in combination with methotrexate in patients with recent onset rheumatoid arthritis (RA), and to assess the long-term safety and maintenance of efficacy after treatment with adalimumab for up to 10 years.

Full description

This study had an initial 2-year double-blind treatment period followed by an 8-year open-label extension period, for a total of up to 10 years study duration. The study was designed to assess the potential of adalimumab + methotrexate to improve signs and symptoms of disease and to inhibit radiographic progression in patients with recent onset (disease duration less than 3 years) rheumatoid arthritis not previously treated with methotrexate. Adalimumab is a human anti-tumor necrosis factor (TNF) monoclonal antibody.

Enrollment: 799 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
• Diagnosis of rheumatoid arthritis (RA) as defined by the 1987-revised American College of Rheumatology (ACR) criteria, with a disease duration less than 3 years, at least 8 swollen joints out of the 66 joints assessed, at least 10 tender joints out of the 68 joints assessed, at least 1 joint erosion or rheumatoid factor (RF) positivity, erythrocyte sedimentation rate (ESR) >= 28 mm/1h or C-reactive protein (CRP) >= 1.5 mg/dl

Exclusion criteria

• Chronic arthritis diagnosed before the age of 16
• Preceding treatment with MTX, cyclophosphamide, cyclosporin, azathioprine or more than 2 other disease-modifying anti-rheumatic drugs (DMARDs)
• Subject previously received anti-tumor necrosis factor (TNF) therapy
• Permanently wheelchair-bound or bedridden patients
• Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
• Female subject who is pregnant or breast-feeding or considering becoming pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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799 participants in 3 patient groups

Adalimumab

Experimental group

Description:

Participants received adalimumab 40 mg subcutaneous injection once every other week and placebo to methotrexate orally once a week during the 2-year double-blind treatment phase and then adalimumab 40 mg every other week for up to 8 years in the open-label extension.

Treatment:

Biological: Adalimumab

Drug: Methotrexate placebo

Adalimumab + methotrexate

Experimental group

Description:

Participants received adalimumab 40 mg subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.

Treatment:

Drug: Methotrexate

Biological: Adalimumab

Methotrexate

Experimental group

Description:

Participants received placebo to adalimumab subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.

Treatment:

Drug: Methotrexate

Biological: Adalimumab placebo