http://pic2.cmt.com.cn/WebImages/Res/20121218/20121218_07b349d6-2637-4801-bdbd-4fb2c4b2a867.pdf

Management of Crohn's Disease in Adults

ACG Clinical Guideline: Management of Crohn’s Disease in Adults

https://www.medigraphic.com/pdfs/gastro/ge-2006/ge063r.pdf

American Gastroenterological Association Institute Technical Review on Corticosteroids, Immunomodulators, and Infliximab in Inflammatory Bowel Disease

Revisión técnica sobre corticosteroides, inmunomoduladores, e infliximab en enfermedad inflamatoria intestinal del Instituto de la Asociación de Gastroenterología Americana

Background
Historically, corticosteroids have been the most commonly used class of medication for induction of remission in Crohn's disease (CD). Corticosteroids down regulate production of inflammatory cytokines and interfere with NF-κB production, thereby blunting inflammatory response.

Objectives
The primary objective was to systematically review the efficacy and safety of traditional corticosteroids (given orally or intravenously) for induction of remission in CD.

Search methods
The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group Specialized Trial Register, and ClinicalTrials.gov. No language restrictions were applied. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched.

Selection criteria
Randomized, controlled clinical trials of traditional, systemic corticosteroids for the induction of remission of active CD were included in this review. Control groups included patients receiving either placebo or 5-aminosalicylates (5-ASA). The study population included patients of any age with active CD (as defined by the study authors or validated clinical activity indices), receiving any formulation of systemically available corticosteroid by any oral or parenteral methods of delivery. The primary outcome was induction of remission of CD. Secondary outcomes included clinical response, change in mean CDAI, adverse events and the proportion of patients withdrawing due to adverse events.

Data collection and analysis
Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.

Main results
Two studies compared corticosteroids to placebo and six studies compared corticosteroids to 5-ASA. Corticosteroids were found to be significantly more effective than placebo at inducing remission in CD (RR 1.99; 95% CI 1.51 to 2.64; P 15 weeks; RR 1.65; 95% CI 1.33 to 2.03; P < 0.00001). Corticosteroids induced adverse events in a higher proportion of patients than placebo (RR 4.89; 95% CI 1.98 to 12.07; P = 0.0006), or low-dose 5-ASA (RR 2.38; 95% CI 1.34 to 4.25; P = 0.003). No difference existed in the proportion of patients experiencing adverse events when steroids were compared to high-dose 5-ASA. Steroids did not induce more study withdrawals due to adverse events than either placebo or 5-ASA.

Authors' conclusions
Corticosteroids are effective for induction of remission in patients with CD, particularly when used for more than 15 weeks. Although corticosteroids cause more adverse events than either placebo or low-dose 5-ASA, these adverse events did not lead to increased study withdrawal in the included studies. Further information is required to determine the optimal duration of treatment and tapering protocol to maximize the efficacy of treatment with corticosteroids. Additionally, further study is required to determine whether corticosteroids are more effective in patients with certain phenotypes or when administered intravenously.

/pdf/traditional-corticosteroids-for-induction-of-remission-in-3yfdura0ix.pdf

Traditional corticosteroids for induction of remission in Crohn's disease

PURPOSE To evaluate treatment response to intravenous (IV) infliximab (IFX) as a first-line therapy in patients hospitalized for severe Crohn's disease and compare it with our earlier data using IV hydrocortisone. METHODS Seventeen cases received IFX (5 mg/kg) and were matched for the same goal of therapy to those who had received hydrocortisone (300 mg/d). The Crohn's and Colitis Foundation of America-International Organization of Inflammatory Bowel Disease (CCFA-IOIBD) score was obtained for the IFX-treated cases on admission and daily and the Crohn's disease activity index (CDAI) score weekly throughout the hospitalization and compared with those who received hydrocortisone. Discharge was guided by the same criteria in both groups. RESULTS For the IFX group, the admission mean CCFA-IOIBD score was 13.5 (+/-4.4). Eight of 17 patients achieved a clinical response with a mean score of 4 (+/-1.5), representing a >or=50% reduction from baseline to discharge. The mean admission score for the hydrocortisone group was 17.75 (+/-7.1) with 13 of 16 achieving a mean score of 4.5 (+/-2.3). The mean discharge score for the 17 IFX patients was 6.9 (+/-3) and for the hydrocortisone group was 5.9 (+/-3.2). Median length of hospitalization for the IFX patients was 4 days (range 1 to 9) and 7.5 (5 to 15) days for the hydrocortisone group (P<0.001). CONCLUSIONS IFX therapy was an effective first-line agent in patients with severe Crohn's disease who require hospitalization and therefore a primary treatment option. Most patients receiving IFX can anticipate a briefer hospitalization than with IV hydrocortisone. Failure of an early response can provide an opportunity to consider an alternate form of therapy sooner with IFX than with hydrocortisone.

A prospective open-label trial of Remicade in patients with severe exacerbation of Crohn's disease requiring hospitalization: a comparison with outcomes previously observed in patients receiving intravenous hydrocortisone.

Infliximab vs. Hydrocortisone for Crohnʼs Disease Patients Requiring Hospitalization: 802

Adrenocorticotrophic hormone (ACTH) and corticosteroids have no maintenance values for inflammatory bowel disease but serve to reduce the severity of disease. The effectiveness of intravenous corticotrophin versus hydrocortisone in ulcerative colitis has been determined including whether previous steroid therapy influenced the better response to one rather than the other, but no such studies have ever been done in Crohn's disease. Eighty-eight patients hospitalized with moderate-to-severe Crohn's disease (Present-Korelitz [P-K] Index -3 to -2 and the International Organisation for the Study of Inflammatory Bowel Disease-Crohn's & Colitis Foundation of America [IOIBD-CCFA] Index, mean 14, range 5-23) were treated in a prospective, randomized, double-blind clinical trial to receive either continuous intravenous infusion of 120 U/day of ACTH (44 patients) or hydrocortisone 300 mg/day (44 patients). Patients were also subdivided into those who received oral steroids during the 30 days prior to intravenous therapy and those who had not. Response was followed on a daily basis and tabulated at 3, 5, and 10 days. Patients were followed from 1-3 years to determine the later status. After 10 days of intravenous therapy 36 of 44 patients (82%) who received ACTH and 41 of 44 patients (93%) who received hydrocortisone fully responded (P-K index +3 and IOIBD-CCFA Index mean of 3). At the end of the study, response to intravenous ACTH and hydrocortisone was not statistically different whether or not patients received oral steroids during the 30 days prior to admission, although the response to IV ACTH tended to be faster at 3 days in those who had received previous steroid therapy. Intravenous ACTH and hydrocortisone are equally effective in achieving therapeutic goals in patients with Crohn's disease who have not achieved results with oral medications. Moreover the response rate was high (mean 88%), serving to buy time for establishment of successful maintenance programs of treatment with oral 5-ASA and immunosuppressive drugs for 69% of patients at 1-3 years.

Intravenous Corticotrophin vs. Hydrocortisone in the Treatment of Hospitalized Patients with Crohn's Disease: A Randomized Double-Blind Study and Follow-Up

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A prospective open-label trial of Remicade in patients with severe exacerbation of Crohn's disease requiring hospitalization: a comparison with outcomes previously observed in patients receiving intravenous hydrocortisone.

Infliximab vs. Hydrocortisone for Crohnʼs Disease Patients Requiring Hospitalization: 802

Intravenous Corticotrophin vs. Hydrocortisone in the Treatment of Hospitalized Patients with Crohn's Disease: A Randomized Double-Blind Study and Follow-Up