Monitoring Crohn’s Disease Using Inflammation Biomarkers and Symptoms Led to Better Patient Outcomes Than Using Symptoms Alone, Mount Sinai Researchers Report
46 percent of patients experienced mucosal healing vs. 30 percent using standard therapeutic strategies
An efficacy and safety study of two treatment models for patients with Crohn’s disease has found that monitoring both inflammation biomarkers and symptoms led to superior outcomes compared to clinical management of symptoms alone.
Mount Sinai researchers found that 46 percent of patients randomly assigned to a “tight control” (TC) protocol of biomarker and symptom monitoring experienced mucosal healing—the complete absence of all ulcerative lesions in all segments of the gut after 48 weeks—compared with 30 percent of patients randomized to clinical management (CM). In addition, a significantly higher proportion of patients in the TC group achieved deep remission and steroid-free remission compared with the CM group.
The trial, known as CALM, “Open-Label, Multi Center, Efficacy and Safety Study to Evaluate Two Treatment Algorithms in Subjects with Moderate to Severe Crohn's Disease” is the first study to demonstrate that monitoring inflammation biomarkers, including C-reactive protein (CRP) and fecal calprotectin, along with clinical symptoms led to superior patient outcomes while using anti-tumor necrosis factor (TNF) therapy (adalimumab/Humira®) compared with symptom-driven decisions alone.
The results of the study will be published online in The Lancet on Tuesday, October 31, at 8:01 pm EDT and will be presented at the United European Gastroenterology Week meeting in Barcelona.
“With this study, we have implemented a new concept of ‘tight control’ of Crohn’s disease, which will change the way that patients will be followed in clinical practice,” said the paper’s lead author, Jean–Frederic Colombel, MD, Director of The Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at The Mount Sinai Hospital and Professor of Medicine and Gastroenterology at the Icahn School of Medicine at Mount Sinai. “Treatment should be based on objective markers of inflammation and not only on symptoms. A patient with Crohn’s disease may do well clinically, but if biomarkers for the disease remain high, we still need to escalate interventions including drugs. This study shows tight control led to more patients experiencing clinical remission, which will ultimately improve their long-term outcomes.”
In the phase 3, multi-center clinical trial, 244 patients with moderate to severe Crohn’s disease were randomly assigned in equal numbers to TC or CM groups after eight weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise from no treatment to adalimumab induction every other week, to every week and finally to both adalimumab and azathioprine every week. The presence of CRP in blood and fecal calprotectin in stool was monitored in the TC group: In the TC group, drugs were escalated to the next step when CRP rose above 5mg/L or fecal calprotectin above250 ìg. In both groups, drugs were also escalated to the next step when patients reported increases in clinical symptoms.
According to Dr. Colombel, further research is needed to demonstrate the long-term effects of the TC approach on Crohn’s disease as measured by shorter hospitalizations, fewer surgeries and complications, and less disability.
“When patients with Crohn’s disease are making therapeutic decisions about starting a drug, or escalating or de-escalating a drug, they can’t base these decisions on symptoms alone,” said Dr. Colombel. “They need objective data including biomarkers and endoscopy results. Ultimately this will disable their disease from progressing.”
This study was supported by NIH NCT01235689. AbbVie, the maker of Humira, funded the study, contributed to design, and participated in the collection, analysis, and interpretation of the data and in preparation and approval of this report. All authors had access to study data, reviewed and approved the final report, and take full responsibility for the accuracy of the data and statistical analysis. The corresponding author had full access to study data and had final responsibility for the decision to submit for publication.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The System includes approximately 6,600 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 13 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally.