Centocor, Inc (HORSHAM, Pennsylvania), a wholly owned subsidiary of Johnson & Johnson and Schering-Plough Corp (KENILWORTH, New Jersey), announced that the European Commission has approved a new indication for Remicade (infliximab) allowing for the treatment of severe, active Crohn's disease (CD) in pediatric patients ages 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator, and primary nutrition therapy, or who are intolerant to, or have contraindications for such therapies. Remicade has been studied only in combination with conventional immunosuppressive therapy. Remicade is the first and only biologic therapy approved in the EU for the treatment of pediatric CD (PCD) and moderate-to-severe ulcerative colitis (UC).
The revised labeling will permit physicians to administer a 5 mg/kg intravenous infusion of Remicade over a 2-hour period, followed by additional 5 mg/kg infusions at 2 and 6 weeks, then every 8 or 12 weeks thereafter. Available data do not support further Remicade treatment in pediatric patients not responding within the first 10 weeks of treatment.
The approval was based on phase III data from a Randomized, multicenter, open-label study to Evaluate the safety and efficacy of Anti-TNFα CHimeric monoclonal antibody (REACH) trial of Remicade in PCD. The REACH trial enrolled 112 patients, all of whom received 6-mercaptopurine (6-MP), azathioprine (AZA), or methotrexate (MTX); 35% of patients with an inadequate response to conventional therapies also received 5 mg/kg infusions of Remicade at weeks 0, 2, and 6. Patients assessed to be in clinical response at week 10 were randomized and received 5 mg/kg Remicade at either q8 weeks or q12 weeks as a maintenance treatment regimen. Patients who lost clinical response during maintenance treatment could receive Remicade at a higher frequency or dose.
The proportion of subjects in clinical response at week 10 was 88.4% (99/112). The proportion of subjects achieving clinical remission at week 10 was 58.9% (66/112). At week 30, the proportion of subjects in the maintenance treatment group in clinical remission was higher in the q8 week (59.6%, 31/52) than in the q12 week (35.3%, 18/51; P = .013). At week 54, the proportion of subjects in clinical remission was 55.8% (29/52) and 23.5% (12/51) in the q8 week and q12 week maintenance groups, respectively (P <.001).
Thirty-two pediatric patients (9 in the q8 week and 23 in the q12 week maintenance group) lost response and received Remicade at a higher dose or more frequently. Twenty-four of these 32 patients (75%) regained clinical response. Of the 22 subjects who had fistulas at baseline, 63.6% (14/22), 59.1% (13/22), and 68.2% (15/22) were in complete fistula response at weeks 10, 30, and 54, respectively, in the combined q8 week and q12 week maintenance group. In addition, statistically and clinically significant improvements in growth rates and in quality of life, as well as a significant reduction in corticosteroid use, were observed.
The following adverse events were reported more commonly in PCD patients in the REACH trial than in adult CD patients: anemia (10.7%), blood in stool (9.7%), leukopenia (8.7%), flushing (8.7%), viral infection (7.8%), neutropenia (6.8%), bone fracture (6.8%), bacterial infection (5.8%), and respiratory tract allergic reaction (5.8%).
Centocor discovered Remicade and has exclusive marketing rights to the product in the US. Schering-Plough markets Remicade in all countries outside of the US, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd, markets the product; Xian-Janssen markets Remicade in China. The US FDA approved Remicade for PCD in May 2006. Nearly 925,000 patients have been treated with Remicade worldwide across all indications including CD, PCD, UC, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.
—A. Techman
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