New Biologic Therapy Helps Children with Crohn's Disease

Crohn's disease is a chronic, debilitating and relapsing disorder characterized by inflammatory destruction of the gastrointestinal tract, most commonly affecting the large and small bowel. (See the related article for general information on this condition). About 400,000 Americans suffer from Crohn's disease, with symptoms including diarrhea, fever, abdominal pain and weight loss. It is estimated than one in every 800 US children has Crohn's disease, usually presenting between 12 and 16 years of age.

Patients with severe Crohn's disease often receive steroids to control inflammation. In addition to the stunted growth and delayed puberty these cause in children, steroids also may cause bone damage including osteoporosis, as well as neurological difficulties, severe acne and moon face. Physicians typically limit steroid use and try to taper patients off steroids while using immunomodulators, which control inflammation but may take several months to become effective. However, many patients are unable to taper off steroids, even when receiving immunomodulator therapy.

In a study by Medical College of Wisconsin researchers, children with active severe Crohn's disease, who had not responded to conventional therapy for over four months and had not been able to taper off their potentially growth-stunting steroid therapy, showed significant improvement and were able to decrease their steroid usage within four weeks of an infusion of a new biologic therapy, infliximab. Biologic therapy involves treatment with substances that can stimulate the immune system to fight off disease more effectively.

The study, reported in the November issue of the American Journal of Gastroenterology (Volume 95 #11), showed that those children with early disease -- up to two years from time of diagnosis -- had a markedly prolonged response to the drug compared with those who were diagnosed with Crohn's disease for longer than two years. No serious, clinically significant adverse effects were shown during the 12-month study of 15 pediatric patients at Children's Hospital of Wisconsin.

"Because Crohn's disease most frequently is diagnosed in adolescents and young adults, optimizing treatment in pediatric patients is crucial. We use corticosteroids to control inflammation, but when these are given on a long-term basis they can have serious side effects that are detrimental to physical and emotional development in adolescents," said Subra Kugathasan, MD, Assistant Professor of Pediatrics and lead investigator of the study. "Early use of infliximab in steroid-dependent children may enable pediatricians to titrate patients off steroids more quickly and may represent an optimal approach that is fast, effective and, especially important in pediatric cases, less prone to significant adverse effects."

Fifteen pediatric patients with severe and persistent refractory Crohn's disease, as defined by their inability to discontinue steroids, lack of response to immuno-modulators, and active disease, were treated with one infusion of infliximab and followed over the next 12 months. All patients remained on immunomodulators during and after the infusion treatment period while investigators sought to determine infliximab's short-term efficacy, safety and duration of response.

"Nearly half of these children were so severely disabled by Crohn's disease that they could not attend school or were actually hospitalized," said Dr. Kugathasan. "Within four weeks of the infliximab infusion, 94% had achieved significant decreases in their disease activity, and by week 10, 67% were in complete remission. One patient who was diagnosed with severe inflammation of the entire gastrointestinal tract showed dramatic intestinal healing five weeks after the infusion, as determined by endoscopy. This study indicates that early use of infliximab may represent an optimal approach to avoiding irreversible tissue damage when children are treated early in the disease process."

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.