Very early treatment with infliximab in addition to methotrexate in early, poor‐prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: Results from a twelve‐month randomized, double‐blind, placebo‐controlled trial

Abstract

Objective. Anti-tumor necrosis factor ␣ agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poorprognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months.Methods. All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months.Results. Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05).Conclusion. Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.Drs.

Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

“…The overall degree of clinical response in this population was similar to findings in previous studies of treatment with infliximab plus MTX in early RA (6)(7)(8). Notably, in 67 of 77 patients (87%) who initially achieved a good response (DAS Յ2.4 for 6 months), this response lasted despite infliximab discontinuation, and MTX could be tapered to a maintenance dosage (discontinuation of MTX was not allowed in the protocol).…”

“…Biologic agents, particularly tumor necrosis factor (TNF) inhibitors, were initially developed to treat patients whose disease remained active despite treatment with conventional DMARDs. More recently, TNF inhibitors were shown to be more effective than methotrexate (MTX) as treatment for patients with newly diagnosed RA (6)(7)(8). To date, the high costs of these drugs and the uncertainties about the risk of adverse effects from prolonged use are among the reasons TNF inhibitors are not the initial therapy for many patients recently diagnosed as having RA (9).…”

Effect of the early use of the anti–tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis

“…Several studies have significantly associated high HAQ scores with work limitations (22). In the early RA study by Quinn et al (23), the infliximab ϩ MTX group achieved an improvement in HAQ and RAQoL scores sig- nificantly faster than the placebo ϩ MTX group. Therefore, those patients who struggle at work should benefit from aggressive treatment to quickly improve symptoms of RA and, subsequently, function (HAQ) and work problems.…”

Extremity magnetic resonance imaging in rheumatoid arthritis: Report of the american college of rheumatology extremity magnetic resonance imaging task force

“…In another small, blinded study comparing outcomes in 20 patients with early RA treated with an "induction regimen" of methotrexate with or without infliximab for 1 year, 1.5T MRIs of the second through the fifth MCP joints were evaluated for evidence of synovitis, bone marrow edema, and erosion (34). Joints were evaluated using the same protocol as in the study described above (10), including the use of intravenous gadolinium enhancement.…”