Navigating childhood and adolescence is tough enough under ideal circumstances. No car, no cash and plenty of homework, not to mention Dad’s bad jokes. It’s enough to make a kid crazy. Now throw into the mix a chronic disease that can destroy the digestive system and you’re standing in the shoes of the young patients seen every day at the Johns Hopkins Pediatric IBD Center.
IBD stands for inflammatory bowel disease, which, like cancer, is actually many diseases grouped under one. The best known IBDs are Crohn’s disease, which can affect any part of the gastrointestinal tract, and ulcerative colitis, which attacks the colon. Even among experienced physicians, IBDs are considered adult diseases– a potentially dangerous assumption, as many of the 140,000 annual pediatric IBD cases often go misdiagnosed for years.
“In the public at large, no one thinks of kids having IBD,” says Maria Oliva-Hemker, director of the Pediatric IBD Center. “Even many pediatricians believe IBD is a disease only of adulthood.”
The initial symptoms – persistent diarrhea, abdominal pain, rectal bleeding and weight loss – can recur each time the disease flares. Controlling these flares is at the heart of Oliva-Hemker’s work. With no cure for Crohn’s, and only a serious surgical intervention – removal of the colon – for curing ulcerative colitis, medications are usually the first course of treatment. However, such medications often call for frequent dosing throughout the day – not an easy task for families. Indeed, the medication non-compliance rate, according to Oliva-Hemker’s latest study in the Journal of Pediatric Gastroenterology & Nutrition (February 2007), is a depressing 33 percent, which helps explain why children suffer repeated outbreaks. Medicines such as steroids and anti-inflammatories effectively push 90 percent of mild to moderate IBD cases into remission, though rarely permanently.
“We have good data that 50 percent of patients either can’t sustain their remission without steroids, or they don’t respond at all,” says pediatric gastroenterologist Carmen Cuffari.
That’s why Oliva-Hemker and Cuffari are now focusing on a new class of medicines that may offer greater efficacy with fewer side effects. These so called “biologics” are genetically engineered mini-missiles that inhibit specific GI enzymes thought to set off inflammatory flares.
Forty percent of children with moderate and severe Crohn’s went into remission using Remicade, after being extremely non-responsive to traditional therapies. Some researchers believe those numbers could jump to a 60–70 percent response rate if Remicade, the first FDA approved biologic for use in Crohn’s, were offered earlier in treatment. It’s also possible that drugs like Remicade could drive milder cases of pediatric IBDs into longer remissions, or be introduced as part of a more effective drug “cocktail.”
With biologics now at their disposal – and some 100 now in development – Oliva-Hemker’s team is researching just how and when to deploy these powerful weapons. Because drug companies and the government don’t collect much pediatric drug data, Oliva-Hemker and her colleagues participate in a consortium of 18 national pediatric IBD centers. That allows them to follow nearly 1,000 pediatric IBD patients, and learn everything from optimal dosing schedules to targeted treatments.
Developing pediatric clinical trials to test these hypotheses is part of the plan. The data is vital because severe IBD in children often presents more aggressively than in adults, and drug efficacy varies depending on age of exposure. Also, children who develop a chronic illness have a greater chance of being exposed to more drugs for longer periods of time than adults. Rare side effects for drugs such as biologics may not show up in FDA approval studies, requiring ongoing monitoring of patients taking biologics.
In a recent editorial for the Journal of Pediatric Gastroenterology and Nutrition, Oliva-Hemker noted that in a very small percentage of pediatric patients, Remicade use was associated with T cell lymphoma and a surprising increase in infections such as tuberculosis. “They have to take the risk/benefit ratio into account,” Oliva-Hemker says.
With a second biologic, Humira, now FDA approved for clinical use in Crohn’s, and Remicade, now also approved for ulcerative colitis, IBD treatments may soon promise longer remissions. Cuffari notes that a pivotal study with non-biologics found that “early, aggressive treatment within six weeks of diagnosis of the disease leads to better long-term clinical response” (Journal of Pediatric Gastroenterology and Nutrition, February 2007) – possibly bringing the center one step closer to its goal.
“We’re looking to alter the ‘natural’ course of the disease,” explains Oliva-Hemker, “so that our young patients can grow up leading active, healthy lives.”