The Infliximab Rheumatoid Arthritis Methotrexate Tapering (iRAMT) Protocol
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of the study was to evaluate the ability of a maintenance dosage regimen of
      infliximab to achieve and sustain at least 40% improvement from baseline in the total joint
      count in patients with active Rheumatoid Arthritis (RA) during methotrexate tapering.
    

Detailed description: 
      Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown etiology that occurs in
      approximately one percent of the population. Current therapy for RA comprises non-steroidal
      anti-inflammatory drugs (NSAIDs) in early stages of the disease, ultimately giving way to
      oral glucocorticoids and the disease-modifying anti-rheumatic drugs (DMARDs) as the disease
      progressively worsens. Therapy with DMARDs (e.g., D-penicillamine, auranofin,
      hydroxychloroquine, azathioprine, methotrexate) is not ideal in that they generally have a
      slow onset of action (measured in months), variable levels of effectiveness, and
      dose-limiting toxicity. Methotrexate (MTX) has become the DMARD of choice of many
      rheumatologists because of its faster mode of action and better record of prolonged use.
      However, despite the use of high doses of MTX, many patients only experience partial relief
      of symptoms and still have features of active disease. The current product labeling provides
      for a range of infliximab doses. Four fixed maintenance dose regimens proved to be safe and
      efficacious in the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT)
      trial. However, the efficacy of incremental dose titration in patients with RA who have not
      achieved or maintained a clinically important improvement from baseline status has not been
      established in a clinical trial setting. Additionally, whether MTX tapering is possible in
      those patients who have achieved a clinically important improvement from baseline status has
      not been demonstrated. The iRAMT trial utilizes a prescribed strategy for infliximab dose
      titration in the event that individuals do not achieve a 40% improvement in the combined
      swollen and tender joint count, or have a disease flare or recurrent worsening. The iRAMT
      trial defines a clinically important improvement as at least a 40% improvement from baseline.
      Once the 40% improvement is achieved, MTX tapering will be initiated as appropriate for the
      specific patient. The primary efficacy endpoint is the number (%) of patients on a
      maintenance dose of infliximab who achieve at least 40% improvement from baseline in the
      combined tender and swollen joint count and tolerate any reduction in MTX dose at Week 54.
      Hence, this trial will provide information regarding an infliximab dose titration strategy as
      well as a MTX tapering schedule in those patients responding to therapy. The iRAMT trial will
      examine, in a manner consistent with clinical practice, if a schedule of infliximab
      maintenance will allow for tapering of MTX to occur. Patients will receive Infliximab
      infusions at a minimum dose of 3 mg/kg at Weeks 0, 2, 6 and every 8 weeks thereafter until
      Week 46. During the study, the dose of infliximab may be increased by single 100-mg vials
      using a specified regimen up to a maximum of 10 mg/kg every 4 weeks.
    

Intervention name(s): infliximab
Intervention type(s): Drug
Intervention MeSH terms: Infliximab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rheumatoid Arthritis; Infliximab infusions; Methotrexate; Remicade