The safety and effectiveness of infliximab products have been established in pediatric patients 6 to 17 years of age for induction and maintenance treatment of CD and UC [see Dosage and Administration (2.2, 2.4) and Adverse Reactions (6.1)]. However, the safety and effectiveness of infliximab products in pediatric patients <6 years of age with CD or UC have not been established. The safety and effectiveness of infliximab products in the treatment of pediatric patients with Ps and juvenile rheumatoid arthritis (JRA) have not been established.

Pediatric Crohn's Disease

The safety and effectiveness of infliximab products have been established for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active CD who have had an inadequate response to conventional therapy. The use of infliximab for this indication is supported by evidence from a randomized, open-label pediatric CD study in 112 pediatric patients aged 6 years and older [see Clinical Studies (14.2)].

Infliximab has been studied only in combination with conventional immunosuppressive therapy in pediatric CD. The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric CD patients have not been established in clinical trials.

Postmarketing cases of HSTCL have been reported in pediatric patients treated with TNF blockers including infliximab products. Due to the risk of HSTCL, a careful risk-benefit assessment should be made when AVSOLA is used in combination with other immunosuppressants in pediatric CD patients [see Boxed Warning and Warnings and Precautions (5.2)].

Pediatric Ulcerative Colitis

The safety and effectiveness of infliximab products for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy have been established. The use of infliximab for this indication is supported by evidence from adequate and well-controlled studies of infliximab in adults with additional safety and pharmacokinetic data from an open-label pediatric UC study in 60 pediatric patients aged 6 years and older [see Dosage and Administration (2.4), Adverse Reactions (6.1), and Clinical Studies (14.4)]. The effectiveness of infliximab in inducing and maintaining mucosal healing in pediatric UC was not established. Although 41 patients had a Mayo endoscopy subscore of 0 or 1 at the Week 8 endoscopy, the induction phase was open-label and lacked a control group. Only 9 patients had an optional endoscopy at Week 54. Approximately half of the patients were on concomitant immunomodulators (AZA, 6-MP, MTX) at study start. 

Due to the risk of HSTCL, a careful risk-benefit assessment should be made when AVSOLA is used in combination with other immunosuppressants in pediatric UC patients [see Boxed Warning and Warnings and Precautions (5.2)].

The longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric UC patients have not been established in clinical trials.

Juvenile Rheumatoid Arthritis (JRA)

The safety and effectiveness of infliximab products in the treatment of pediatric patients with juvenile rheumatoid arthritis (JRA) have not been established.

The safety and efficacy of infliximab in patients with JRA were evaluated in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension, for a maximum of 44 weeks. Patients with active JRA between the ages of 4 and 17 years who had been treated with MTX for at least 3 months were enrolled. Concurrent use of folic acid, oral corticosteroids (≤0.2 mg/kg/day of prednisone or equivalent), NSAIDs, and/or disease-modifying antirheumatic drugs (DMARDs) was permitted.

Doses of 3 mg/kg infliximab or placebo were administered intravenously at Weeks 0, 2 and 6. Patients randomized to placebo crossed over to receive 6 mg/kg infliximab at Weeks 14, 16, and 20, and then every 8 weeks through Week 44. Patients who completed the study continued to receive open-label treatment with infliximab for up to 2 years in a companion extension study.

The study failed to establish the efficacy of infliximab in the treatment of JRA. Key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults. Additionally, a higher rate of clearance of infliximab was observed than had been observed in adults.

Population pharmacokinetic analysis showed that in pediatric patients with JRA with a body weight of up to 35 kg receiving 6 mg/kg infliximab and pediatric patients with JRA with body weight greater than 35 kg up to adult body weight receiving 3 mg/kg infliximab, the steady state area under the concentration curve (AUCss) was similar to that observed in adults receiving 3 mg/kg of infliximab.

A total of 60 patients with JRA were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. The proportion of patients with infusion reactions who received 3 mg/kg infliximab was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks. The most common infusion reactions reported were vomiting, fever, headache, and hypotension. In the 3 mg/kg infliximab group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions). In the 6 mg/kg infliximab group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction. Two of the 6 patients who experienced serious infusion reactions received infliximab by rapid infusion (duration of less than 2 hours). Antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg infliximab compared with 12% (6/49) of patients who received 6 mg/kg.

A total of 68% (41/60) of patients who received 3 mg/kg infliximab in combination with MTX experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg infliximab in combination with MTX over 38 weeks. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia. Other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient.