Centocor, Inc. (HORSHAM, Pa.), a wholly owned subsidiary of Johnson & Johnson, announced that the US FDA has expanded marketing approval for Remicade® (infliximab) to inhibiting the progression of structural damage and improving physical function in patients with active psoriatic arthritis (PsA), in addition to reducing the signs and symptoms of active arthritis. 

Centocor's supplemental Biologics License Application (sBLA) for Remicade was based on 1-year data from the double-blind, placebo-controlled trial IMPACT 2 and 2-year data from the double-blind, placebo-controlled trial IMPACT. The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) was a phase IIb randomized, double-blind, placebo-controlled study that involved 104 patients with active PsA (defined as affecting at least five joints) who had responded inadequately to at least one disease-modifying anti-rheumatic drug (DMARD). The Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2 (IMPACT 2) was a phase III, randomized, double-blind, placebo-controlled study of 200 patients with active PsA. The study evaluated the safety and efficacy of Remicade in patients who had an inadequate response to DMARDs or nonsteroidal anti-inflammatory drugs (NSAIDs).

One-year radiographic analyses from IMPACT 2 showed that treatment with Remicade resulted in significantly greater inhibition of the progression of structural damage, compared with placebo (as measured by the change from baseline in van der Heijde-Sharp [vdH-S] score modified for PsA by adding measurement for distal interphalangeal joints of the hands). At week 54, patients who received a full 54-week regimen of Remicade experienced a mean change of -0.94 (+/- 3.40) from baseline, compared with an average change of 0.53 (+/- 2.60) in patients who crossed over from placebo to Remicade (P = .001) at week 16 or 24.

Remicade-treated patients demonstrated significant improvement in physical function as measured by the Health Assessment Questionnaire (HAQ). As early as week 14, patients in the REMICADE group experienced a median improvement of 43%, compared with 0% in the placebo group (P <.001), and results were maintained through 1 year. At week 54, there was a median 50% improvement in HAQ score from baseline in the group randomized to Remicade, and a 46% improvement in placebo patients who switched to Remicade. At week 54, 59% of Remicade randomized patients and 53% of placebo patients who crossed over to Remicade had improvement in HAQ by >e;0.3 scores, indicating clinically meaningful improvement in physical function.

In addition, long-term Remicade data showed sustained efficacy in the psoriatic component of the disease. Approximately 64% of Remicade-treated patients in IMPACT maintained at least a 75% improvement from baseline in the skin component of the disease as assessed by the Psoriasis Area Severity Index (PASI 75) through 2 years, and 48% of Remicade-treated patients in IMPACT achieved PASI 90, or near total skin clearance, through 2 years.

Remicade has received European Union approval, in combination with methotrexate, for the treatment of active and progressive PsA in patients who have responded inadequately to DMARDs. Additionally, the European Commission has recently approved the use of Remicade for the treatment of active and progressive PsA in patients who have responded inadequately to DMARDs to be used in combination with methotrexate or alone in patients who show intolerance to methotrexate or in whom methotrexate is contraindicated.

Remicade is a chimeric IgG1 anti-TNF-alpha monoclonal antibody composed of human constant and murine variable regions administered by intravenous infusion by healthcare professionals in the clinic or office setting. In PsA, Remicade is a 2-hour infusion (5 mg/kg) administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, Remicade patients may require as few as six treatments each year.

—A. Techman