FDA Okays Infliximab for Pediatric Ulcerative Colitis

September 23, 2011

September 23, 2011 (UPDATED October 4, 2011) — The US Food and Drug Administration (FDA) approved infliximab (Remicade, Janssen Biotech) to treat moderately to severely active ulcerative colitis (UC) in children older than 6 years who have not responded adequately to conventional therapy.

Infliximab, a type of tumor necrosis factor (TNF)-α blocker, reduces signs and symptoms of UC and maintains clinical remission. It works by suppressing the immune system and blocking the activity of TNF, a substance that can cause inflammation and trigger autoimmune diseases.

The drug was previously approved for treating UC in adults, Crohn's disease in adults and children older than 6 years, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis in adults.

An FDA advisory committee in July recommended approving infliximab for children but voiced concerns about the drug's safety, especially with long-term use.

Boxed Warnings

Its label has a boxed warning for increased risk for serious infections leading to hospitalization or death, including opportunistic infection, tuberculosis, bacterial sepsis, and invasive fungal infections including histoplasmosis. The FDA had issued a previous alert regarding bacterial infections associated with drugs such as infliximab and other TNF-α blockers.

The boxed warning also notes some reports of lymphoma and other malignant diseases, some of which were fatal, in children and adolescents treated with TNF-α blockers, including infliximab. Also reported with infliximab and other TNF-α blockers were postmarketing cases of hepatosplenic T-cell lymphoma, a rare, fatal type of T-cell lymphoma. All of these cases were reported in patients (mostly adolescent or young adult men) with Crohn's disease and UC treated with azathioprine or 6-mercaptopurine concurrently with infliximab, at diagnosis or before diagnosis.

Common Adverse Events

The most common adverse events with infliximab, occurring in more than 10% of patients, are worsening of UC, upper respiratory tract infections, infusion-related reactions, abdominal pain, and headache.

Administration of the Drug

"There are serious risks associated with [infliximab's] use," said Donna Griebel, MD, director of the Division of Gastroenterology and Inborn Errors Products in the FDA's Center for Drug Evaluation and Research, in a press release. "Patients and their families should always discuss with their physician the risks and benefits of using a medication before deciding to start treatment."

The FDA is advising clinicians that children should be caught up on all of their vaccinations before starting infliximab therapy, and children should not receive live vaccines while taking the drug.

Infliximab should not be given during an active infection. If an infection develops while the patient is taking infliximab, careful monitoring is indicated, and the drug should be stopped if the infection becomes serious. For patients who reside in or travel to regions where mycoses are endemic and who develop a systemic illness while taking infliximab, empiric antifungal therapy should be considered.

Clinical Trial Results

Clinical trials showed some differences in the adverse reactions seen in pediatric patients receiving infliximab vs those seen in adults with Crohn's disease. Compared with adult patients with Crohn's disease receiving a similar treatment regimen, children given 5 mg/kg of infliximab were more likely to have anemia (11%), blood in the stool (10%), leukopenia (9%), flushing (9%), virus infection (8%), neutropenia (7%), bone fracture (7%), bacterial infection (6%), and respiratory tract allergic reactions (6%).

In Study Peds Crohn's, 56% of randomly assigned pediatric patients had infections, as did 50% of adult patients in Study Crohn's I. Infections were reported more frequently for patients in Study Peds Crohn's, who received infusions every 8 weeks vs every 12 weeks (74% vs 38%, respectively). Serious infections were reported for 3 patients in the every-8-week maintenance treatment group and 4 patients in the every-12-week group. Upper respiratory tract infection and pharyngitis were the most commonly reported infections, and abscess was the most commonly reported serious infection.

Clinical trials in children with Crohn's disease also showed infusion reactions in 18% of randomly assigned patients, with no striking difference between treatment groups, and development of antibodies to infliximab in 3%. Liver function abnormalities were also noted, with elevations in alanine transaminase levels up to 3 times the upper limit of normal in 18%, alanine transaminase elevations of 3 or more times the upper limit of normal in 4%, and elevations of 5 or more times the upper limit of normal in 1%.

More information about infliximab is available on the agency's Web site.

Laurie Barclay, MD, contributed to this synopsis.

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