Monitoring Of Severe Crohn's Colitis Treated With Intravenous Corticosteroids By C-Reactive Protein: Results Of A Prospective Study
S Ouerdiane, M Serghini, S Karoui, J Boubaker, A Filali
c-reactive protein, crohn's disease
S Ouerdiane, M Serghini, S Karoui, J Boubaker, A Filali. Monitoring Of Severe Crohn's Colitis Treated With Intravenous Corticosteroids By C-Reactive Protein: Results Of A Prospective Study. The Internet Journal of Gastroenterology. 2008 Volume 7 Number 2.
Intravenous corticosteroid is the first line treatment of acute severe colitis in Crohn's disease (1). Recently, treatment by intravenous cyclosporine had constituted a great progress in acute colitis management, avoiding early colectomy in 80% of cases (2). Nevertheless, few studies analyse predictive factors for poor response to intravenous glucocorticosteroid treatment in inflammatory bowel disease, concerning most of the time ulcerative colitis. The results were discordant (3,4,5,6,7).
The aim of our study is to identify predictive factors of poor response to intravenous glucocorticosteroid treatment in patients with acute severe Crohn's disease colitis. This will enable us to define a group of patients in whom a more aggressive medical treatment should be considered at an early stage.
Material And Methods
All patients admitted for management of acute severe Crohn's colitis between January 1990 and June 2004 were included. A severe episode of Crohn's disease was defined according to the modified Truelove and Witts (8) criteria and/or to endoscopic findings classified according to Carbonnel et al. (9). Patients who presented with complications (toxic megacolon, perforation, massive bleeding) underwent emergency colectomy without medical treatment were not included in the present study.
All patients receive intravenous glucocorticosteroid treatment (hydrocortisone 300 to 400 mg/day) associated with bowel rest, peripheral parenteral nutrition and a triple intravenous antibiotherapy including cephalosporin, aminoglycoside, and metronidazole.
Surveillance of the patients includes clinical, biological and radiological tools (daily abdominal radiography). An endoscopic control wasn't performed systematically.
CRP and erythrocyte sedimentation rate (ESR) levels were assessed at the 3 rd day after treatment initiation.
Response to intensive intravenous treatment was defined by clinical improvement especially by a decrease in bloody stool frequency. Failure of intensive intravenous treatment was defined as no change of clinical symptoms, deteriorations or complications under treatment.
Clinical data was analyzed by SPSS 8.0. Qualitative variables were compared by chi2 test or Fisher's exact test. Quantitative variables were compared by Student's t test. Univariate analyses were initially performed to identify potential determinants of outcome. Forward stepwise multiple logistic regressions was then employed to identify predictive factors associated with our outcomes. A
A total of 51 patients (34 female and 17 male) fulfilled the inclusion criteria. The median age at presentation was 31,7 years. All patients were treated with standard medical therapy of intravenous corticosteroids (hydrocortisone 400 mg/day). ESR was assessed at the 3 rd day after treatment initiation in 39 patients (77%). CRP was assessed before starting treatment in 26 (51%) and at day three in 24 (47%) patients.
Predictive factors of therapeutic response
Response to intensive intravenous treatment was achieved in 35 of 51 patients (69%). Failure of medical therapy occurs in 16 patients (31%). In univariate analysis, parameters predicting failure of medical treatment were the lack of decrease of ESR value by 50% at third day of therapy (p=0,001 OR [IC95%]: 0,46 [0.32 - 0.67]) and the lack of decrease of CRP level by 50% at third day of therapy (p<0,0001 OR [ IC95%]: 0.01 [0.02 - 0.30]). In multivariate analysis, the only independent factor predictive of treatment failure found was the lack of decrease of CRP level by 50% at third day of therapy (p=0,001 OR [IC95%]: 0,79 [0.45 - 0.95]).
Medical treatment failure was observed in 31% of the cases. This result is similar to what is observed in the most recent studies (7). Nevertheless, our study is particular in regard of the great number of Crohn's disease patients included comparing to the other studies in the literature, even though the most recent ones (5, 7).
The definition of predictive factors for treatment refractoriness is important considering the bad prognosis of acute severe colitis and the increased risk of life-threatening complications due to prolonged corticosteroid treatment (10).
Second-line therapy was previously represented by colectomy, currently by intravenous cyclosporine (2 mg/Kg/day) or infliximab (5mg/kg). Cyclosporine proved it's effectiveness in management of severe acute ulcerative colitis (11).
Infliximab is approved for the treatment of moderate to severe Crohn's disease, as well as for fistulizing disease (12). The efficacy of infliximab has been proven, both in randomized, controlled trials and in the clinical setting and has become a mainstay in the treatment for refractory Crohn's disease
Travis et al. show in their study that the decrease of CRP levels at the 3 rd day after treatment initiation seems to have a strong predictive value of treatment responsiveness (3). These results were not confirmed by more recent studies (5,7).
In our study, decrease of CRP level of more of 50% at the 3 rd day of treatment was correlated to a good response of medical therapy. An initially low CRP level had a predictive value for treatment failure. This result wasn't found in other studies, probably due to the lack of studies about Crohn's colitis. Nevertheless, similar result were found by Louis et al. (13) studying the response of Crohn's colitis to infliximab. In this study, the patients who respond to infliximab had a raised initial CRP level if compared to the non-responders (16,8mg/l vs 9,6mg/l, p=0,02). In a recent study, CDP-571, a more humanized alpha plus anti-tumor necrosis factor than infliximab, had not shown it's superiority in regard to placebo in patients with a CRP level > 10mg/l (14).
In conclusion, our study is the first Tunisian study attempting to assess predictive factors for response to intravenous corticosteroids in acute severe colitis in Crohn's disease. CRP measurement before and at the 3 rd day of treatment initiation had to be systematically done to better identify patients at high risks to resist to corticosteroid treatment and need cyclosporine or colectomy.
Dr Sami Karoui Department of Gastroenterology A La Rabta Hospital. 1007 Tunis. Tunisia. Tel: +21671578794 Fax: +21671560522 Mail: email@example.com