Highlights in Clinical IBD
Research presentations at this year's Digestive Disease Week (DDW) offered numerous insights on inflammatory bowel disease, including novel therapeutic approaches to ulcerative colitis and Crohn disease.
Prior data from Israeli Army recruits and a European registry suggested that serologies associated with Crohn disease could predict the subsequent development and phenotype of Crohn disease.
Choung and colleagues presented a subset analysis of the Proteomic Research and Discovery in Crohn's disease Translational Science (PREDICTS) Study. They evaluated the longitudinal status of serologic markers from 100 US Army personnel with incident Crohn disease. Samples were obtained from the Department of Defense Serum Repository for each participant at approximately 2, 4, and 6 years prior to diagnosis and at diagnosis. The samples were tested for 6 markers: ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, and anti-FlaX. They evaluated the relationships between Crohn disease-associated antibodies and both complicated and uncomplicated Crohn disease.
The investigators found that ASCA-IgA, ASCA-IgG, anti-A4-Fla2, and anti-FlaX titers prior to diagnosis were higher in complicated Crohn disease compared with uncomplicated disease. Median survival decreased from first positive serum to complication as the measures of marker accumulation increased. Notably, the presence and accumulation of serum markers were detectable well before the diagnosis of Crohn disease predicted the development of later complications.
The confirmation of abnormal serologic markers preceding the diagnosis of inflammatory bowel disease (IBD) suggests that individuals who are at risk might be able to be diagnosed in a preclinical phase. Eventually, further diagnostics or interventions in individuals before the development of symptoms could be considered (eg, pre-diabetes or pre-hypertension).
After the diagnosis of ulcerative colitis is confirmed, one of the long-term risks of disease progression is cancer. Prior studies have identified various risk factors for the development of cancer in the setting of ulcerative colitis, including the extent of colitis, the presence of primary sclerosing cholangitis, onset at a young age, and the presence of persistent inflammation.
Previous observations suggested that the persistence of histologic crypt architectural distortion was a hallmark of chronic ulcerative colitis (CUC) and differentiated CUC from acute self-limited colitis. Most recently, evidence from the University of Chicago suggests that complete histologic normalization of the mucosa is achievable in CUC with more effective therapies. The investigators looked at whether patients in clinical remission who achieved complete histologic normalization were at a lower risk for clinical relapse compared with patients with residual histologic activity or patients with histologic quiescence (ie, absent acute inflammation but with residual crypt architectural distortion). They followed 300 patients who had undergone colonoscopic evaluations, of whom 77 developed a clinical relapse. The hazard ratio for clinical relapse was greatest for patients with residual histologic activity compared with patients who had complete histologic normalization. The hazard ratio for relapse was also greater for patients with histologic quiescence compared with patients who had complete histologic normalization. No other demographic, disease, or medication-related characteristics were significantly associated with clinical relapse.
Additional support for the relevance of complete histologic normalization as a target comes from a retrospective study of adult patients with ulcerative colitis who had quiescent endoscopic disease and were followed for at least 12 months. Among 77 patients, time to relapse was shorter in those with residual histologic activity. On multivariate analysis, the presence of basal plasmacytosis was associated with a shorter time to relapse and with disease relapse by 18 months.
Research presentations at this year's Digestive Disease Week (DDW) offered numerous insights on inflammatory bowel disease, including novel therapeutic approaches to ulcerative colitis and Crohn disease.
Advances in Early Diagnosis of Crohn Disease
Prior data from Israeli Army recruits and a European registry suggested that serologies associated with Crohn disease could predict the subsequent development and phenotype of Crohn disease.
Choung and colleagues presented a subset analysis of the Proteomic Research and Discovery in Crohn's disease Translational Science (PREDICTS) Study. They evaluated the longitudinal status of serologic markers from 100 US Army personnel with incident Crohn disease. Samples were obtained from the Department of Defense Serum Repository for each participant at approximately 2, 4, and 6 years prior to diagnosis and at diagnosis. The samples were tested for 6 markers: ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, and anti-FlaX. They evaluated the relationships between Crohn disease-associated antibodies and both complicated and uncomplicated Crohn disease.
The investigators found that ASCA-IgA, ASCA-IgG, anti-A4-Fla2, and anti-FlaX titers prior to diagnosis were higher in complicated Crohn disease compared with uncomplicated disease. Median survival decreased from first positive serum to complication as the measures of marker accumulation increased. Notably, the presence and accumulation of serum markers were detectable well before the diagnosis of Crohn disease predicted the development of later complications.
The confirmation of abnormal serologic markers preceding the diagnosis of inflammatory bowel disease (IBD) suggests that individuals who are at risk might be able to be diagnosed in a preclinical phase. Eventually, further diagnostics or interventions in individuals before the development of symptoms could be considered (eg, pre-diabetes or pre-hypertension).
Histologic Normalization in Ulcerative Colitis and Rate of Clinical Relapse
After the diagnosis of ulcerative colitis is confirmed, one of the long-term risks of disease progression is cancer. Prior studies have identified various risk factors for the development of cancer in the setting of ulcerative colitis, including the extent of colitis, the presence of primary sclerosing cholangitis, onset at a young age, and the presence of persistent inflammation.
Previous observations suggested that the persistence of histologic crypt architectural distortion was a hallmark of chronic ulcerative colitis (CUC) and differentiated CUC from acute self-limited colitis. Most recently, evidence from the University of Chicago suggests that complete histologic normalization of the mucosa is achievable in CUC with more effective therapies. The investigators looked at whether patients in clinical remission who achieved complete histologic normalization were at a lower risk for clinical relapse compared with patients with residual histologic activity or patients with histologic quiescence (ie, absent acute inflammation but with residual crypt architectural distortion). They followed 300 patients who had undergone colonoscopic evaluations, of whom 77 developed a clinical relapse. The hazard ratio for clinical relapse was greatest for patients with residual histologic activity compared with patients who had complete histologic normalization. The hazard ratio for relapse was also greater for patients with histologic quiescence compared with patients who had complete histologic normalization. No other demographic, disease, or medication-related characteristics were significantly associated with clinical relapse.
Additional support for the relevance of complete histologic normalization as a target comes from a retrospective study of adult patients with ulcerative colitis who had quiescent endoscopic disease and were followed for at least 12 months. Among 77 patients, time to relapse was shorter in those with residual histologic activity. On multivariate analysis, the presence of basal plasmacytosis was associated with a shorter time to relapse and with disease relapse by 18 months.
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