ImproveCareNow (ICN) is excited to share the findings from a years-long clinical trial COMBINE (Clinical Outcomes of Methotrexate Binary treatment with INfliximab or adalimumab in practice). The aim of this trial was to study if treatment with a single anti-TNF medication (infliximab and adalimumab) or dual therapy that includes methotrexate is more effective in children with moderate to severe Crohn’s disease.   

ImproveCareNow has been integral to this clinical trial from the beginning, including leading a research prioritization project in which the aim of this study was a top priority for members of the ICN community, to voting for the name of the study at the 2015 Community Conference. ICN care centers recruited for participation in this trial were vital to its success.  

Below is an excerpt from an article highlighting the key takeaways of this important trial from Principal Investigator Mike Kappelman, MD, MPH’s care center, University of North Carolina at Chapel Hill.  


A significant clinical trial under the direction of Michael Kappelman, MD, MPH, professor of pediatrics at UNC School of Medicine, found that patients receiving the tumor necrosis factor inhibitor adalimumab combined with a low dose of methotrexate, a second immunosuppressant, did better than those treated with adalimumab alone. However, patients initiating infliximab, another tumor necrosis factor inhibitor, had similar outcomes with or without methotrexate. 

Their findings were published in Gastroenterology, the leading journal in the field of gastrointestinal disease. 

Adalimumab and infliximab, the key drugs of interest, belong to a class of medications called anti-inflammatory tumor necrosis factor (TNF) inhibitors. These medications suppress the body’s natural response to TNF, a protein which is produced by white blood cells during inflammatory events. Adalimumab was approved by the Food and Drug Administration in 2014 for treatment in pediatric patients with Crohn’s disease, whereas infliximab was approved in 2006. 

“We know that both adalimumab and infliximab have proven to be effective and safe,” said Kappelman. “We also know that they that they don’t work for all patients and don’t work forever. This pivotal trial comparing anti-TNF alone or in combination with methotrexate has provided clear results that can immediately impact patient care.” 

The clinical trial had been in the works for a decade. Starting with the important decision of which research question was the most urgent and pressing need, Kappelman then engaged key stakeholder groups through a collaboration with ImproveCareNow, an international pediatric network that brings together medical professionals, patients, and families to advance care through research and quality improvement, support for psychosocial functioning and mental health, and escalating initiatives to address disparities, equity, and inclusivity. 

David Wohl, MD, professor of medicine in the Division of Infectious Diseases in UNC’s Department of Medicine, joined ImproveCareNow soon after his son was diagnosed with pediatric Crohn’s disease at nine years old. He was surprised at how little evidence there was behind treatment decisions. 

“I became vocal about the ‘data desert’ parents like me have to wander through to find answers,” said Wohl. “I immediately joined as a parent representative and became active in the organization and at our UNC site. My superpower was not only being a parent of a child with IBD, but also a clinician-researcher.” 

After Wohl’s son started seeing Kappelman for clinical care, they spoke about a need for better clinical trial data. Kappelman then approached Wohl with an idea, which would later become the landmark clinical trial. Subsequently, Wohl assumed a lead role in patient and parent engagement and enrollment, along with Lisa Pitch from Nevada and other parents through ImproveCareNow. 

“To see the study now provide us with a clear answer about what medicines work best in kids with Crohn’s is incredibly gratifying,” said Wohl. “It is truly a game-changer.” 


Read the entire article at UNC Health: Researchers Announce Findings from Landmark Clinical Trial for Pediatric Crohn’s Disease 

Learn more about the COMBINE Trial and other Current Research approved by the ImproveCareNow Research Committee.  

Read the latest Research Explained LOOP blog post about COMBINE. 


About ImproveCareNow 

ImproveCareNow is a Learning Health Network dedicated to transforming care, health and costs for all children and youth with Crohn’s disease and ulcerative colitis (Inflammatory Bowel Disease or IBD) by building a sustainable collaborative chronic care network. We are enabling patients, families, clinicians and researchers to work together in a learning health care system to accelerate innovation, discovery and the application of new knowledge. We invite everyone interested in getting kids with IBD better right now to join us. 

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