A few recent articles make a strong argument for collaborative networks, like ImproveCareNow, to improve data collection to determine the most effective therapies.
- Kierkus J, et al. JPGN 2015; 60: 580-85.
- Audu GK, et al. JPGN 2015; 60: 586-91
- Dotson JL, et al. Inflamm Bowel Dis 2015; 21: 1109-14
- Saps M, et al. JPGN 2015; 60: 645-53.
A brief description of each study.
1. This study presented a multi-center randomized open-label trial of 99 pediatric patients with Crohn’s disease (CD) who were administered infliximab (IFX) along with an immunomodulator (azathioprine or methotrexate). After a 10 week induction, 84 were randomized to either monotherapy for 54 weeks or dual therapy for 26 weeks. The authors did not find significant differences in response between the groups. However, they reached a conclusion: “Twenty-six weeks likely represent (sic) the safe duration of combined IFX/immunomodulator therapy in our sample of pediatric patients with CD.”
2. The second study described three cases of chronic recurrent multifocal ostesomyelitis (CRMO) associated with inflammatory bowel disease. They tried to identify all pediatric cases in UK in the last 10 years. (As an aside, I have treated one teenager with CRMO and ulcerative colitis.)
3. The third study is a retrospective single center of 30 patients with pediatric Crohn’s disease (CD) who developed intra-abdominal abscesses (IAA) over a 12-year period. The authors note that this is “the largest single-center review of children and adolescents with CD and IAA to date.” Yet due to the small sample size, the study provides little guidance on this important medical problem; there were no predictors of successful medical or percutaneous drainage therapy. In addition, with the increasing use of biologics, the authors note that “the issue of which patients will eventually require surgery is even less clear.” Changes in imaging (eg. MRE) and changes in medical management (eg. more enteral nutrition and less corticosteroids) are not discussed.
4. The fourth study is a comprehensive review of randomized placebo-controlled pharmacological clinical trials in children with functional abdominal pain disorders. They found “no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous…We found a considerable risk of bias in most studies…There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures.”
Each of these studies makes a compelling argument for collaborative research networks. The first study had a relatively small number of patients, short follow-up period, lack of blinding, and numerous methodological limitations. How did the authors determine that 26 weeks was the time to stop dual therapy? Among adults with CD, a well-designed SONIC study (NEJM 2010; 362: 1383) showed the superiority of dual therapy during the study period. In children, because of concerns about thiopurine safety, the best approach is still unclear. The second study identified only three patients despite examining a large population. Similarly, the third study describes 30 patients with a common complication of CD but provides little insight.
The fourth study is a cautionary tale illustrating the lack of progress due to the absence of collaborative research. Reports indicate a high prevalence of functional abdominal pain; one study indicated that abdominal pain affects “38% of school children weekly” (J Pediatr 2009; 154: 322-6). In fact, studies on the high prevalence of this disorder dates back for 60 years (Apley, 1975; Apley & Hale, 1973; Apley & Naish, 1958). Despite the prevalence of this problem, the data for all of the treatments is poor. The lack of progress in defining treatments for functional abdominal pain is multifactorial, including the following:
- Cost: For many of the available treatments, there is not a financial incentive to conduct research.
- Biomarker: lack of objective markers for improvement
- Disease Stigma: many people attribute functional disorders as being due solely to psychological factors
- Physician Champions: in pediatric gastroenterology, it took concerted physician efforts over many years to develop ImproveCareNow. Similar physician champions would be needed to improve the outcomes for children with functional disorders
Bottomline: While ImproveCareNow has a lot of work ahead including improving data reliability and ascertaining accurate outcome measures, I think the effort is forward-thinking and will make a difference in understanding and treating children with IBD. ImproveCareNow has more than 600 participating pediatric gastroenterologists and more than 20,000 patients. What I would like to see is a sister network to address the morbidity from functional disorders so that in 60 years (or sooner), we will be better equipped to treat children with abdominal pain that is not due to IBD.
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