Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease-do we have reliable markers?

Abstract

Treatment refractoriness is a severe problem in the management of patients with ulcerative colitis and Crohn's disease. Despite some promising new therapeutic approaches, corticosteroids are still the preferential primary treatment for moderate to severe Crohn's disease and of severe ulcerative colitis. However, clinical response to corticosteroids varies, and many patients are resistant to such treatment. Since corticosteroids have frequent and even severe side effects, and toxicity increases with chronic steroid intake, factors predictive of response to such treatment would be very helpful for decisions on further management of these patients. At least in severe attacks of ulcerative colitis, the consensus seems to be that a high frequency of bowel movements as well as a high C‐reactive protein and low serum albumin recorded after a few days of intensive medical treatment are important signs for early prediction of treatment failure in the majority of the patients. In Crohn's disease thus far, data on predictive factors are conflicting. No reliable marker with sufficient predictive value for treatment refractoriness could be identified. This might be due to the tremendous heterogeneity of Crohn's disease with many clinical phenotypes, which requires subgroup analysis with sufficient numbers of patients. Corticosteroids as well as other immunomodulating and immunosuppressive medications interfere with the immune system, which plays a central role in the mediation of intestinal inflammation. Treatment refractoriness might have its origin in specific immunological peculiarities eventually reflected in abnormal immunological, biochemical, and clinical parameters. Further exploration of those parameters to predict treatment refractoriness in patients with ulcerative colitis or Crohn's disease is of great clinical importance for safe and efficient management of patients.

What Determines the Later Clinical Course of Patients Who Do Not Undergo Colectomy at the First Attack A Japanese Cohort Study on Ulcerative Colitis

“…Previous reports have indicated that a high frequency of bowel movements after intensive medical treatment is an important predictor of treatment failure [1,2,3,4]. In addition, high C-reactive protein (CRP) [4,5] and low serum albumin [2,6] levels have also been reported as significant predictive factors.…”

“…Second, treatment failure following one severe episode, defined as the necessity for colectomy, was the only outcome analyzed in those previous studies. Thus, prognostic factors for long-term disease course have not been documented for patients in complete remission, or for whom surgical intervention was not necessary after one severe episode of UC [1,4]. …”

Low serum albumin at admission is a predictor of early colectomy in patients with moderate to severe ulcerative colitis

“…Previous studies have reported that the predictors of induction therapy failure include a high frequency of bowel movements after intensive induction therapy and a high C‐reactive protein (CRP) level 1–5 . Furthermore, disease activity at diagnosis and lower serum levels of hemoglobin and albumin after the first induction therapy have also been reported as significant predictors of relapse and colectomy 6 .…”

Role of Biomarkers in the Study and Management of Inflammatory Bowel Disease

“…115 In severe attacks of UC, high CRP along with high stool frequency and lowserum albumin have been associated with higher likelihood of failure of medical therapy. 113 The same predictive value of CRP seems to be true for CD as well. 116 High CRP 1 year after diagnosis of either UC or CD has also been reported to be a predictive factor for surgery within the subsequent 4 years.…”

“…107 Likewise, another study using the same retrospective 12-to 18-month design was performed in 71 patients with CD by GETAID, with strong predictive value being noted for both increased ESR and CRP. 108 In addition, the potential role of fecal biomarkers is being widely investigated as a predictor of clinical relapse of IBD, 60,87,[109][110][111] and more specifically as a surrogate for endoscopic assessment of postoperative recurrence of CD, 82,83,112 as well as for assessment of response to therapy, 113 as discussed immediately below.…”