scholarly journals Infliximab for the Treatment of Crohn'S Disease: Review and Indications for Clinical Use in Canada

2001 ◽  
Vol 15 (6) ◽  
pp. 371-375 ◽  
Author(s):  
Remo Panaccione
Keyword(s):  
Crohn’S Disease ◽  
Abdominal Pain ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Activity Index ◽  
Significant Risk ◽  
Inflammatory Disorder ◽  
Aminosalicylic Acid ◽  
Onset Of Action ◽  
Necrosis Factor Alpha

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. It may affect any portion of the gastrointestinal tract from the mouth to the anus. Symptoms typically include cramping abdominal pain, diarrhea (which may be bloody) and nausea. As the severity of the illness worsens, patients may experience constant abdominal pain, vomiting, weight loss and fever. From the perspective of the patient, disease symptoms significantly impair quality of life, and interfere with their work environment and activities of daily living. Unfortunately, there is no cure for Crohn's disease. Patients experience a chronic, relapsing course characterized by recurrent flares of their disease. Conventional medical treatment of Crohn's disease includes the use of non-specific anti-inflammatory drugs (5-aminosalicylic acid agents, prednisone, budesonide), immunosuppressives (6-mercaptopurine, azathioprine, methotrexate) and antibiotics. A variable onset of action, incomplete response rates and a significant risk of adverse effects characterize current therapies. Although surgery is frequently used to treat complications or medically refractory disease, postoperative recurrence is a common problem. Infliximab, a murine chimeric monoclonal antibody directed toward tumour necrosis factor-alpha, is a highly effective treatment of active Crohn's disease. In randomized, placebo-controlled clinical trials, 33% of patients treated with infliximab 5 mg/kg achieved remission (Crohn's Disease Activity Index score less than 150), compared with only 4% of those receiving placebo (P<0.001). Additionally, infliximab is the only drug therapy shown to be effective for the treatment of fistulizing Crohn's disease. In studies done to date, infliximab appears to be well tolerated and has a favourable side effect profile.

scholarly journals Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn’s disease: a retrospective study

2021 ◽  
Vol 14 ◽  
pp. 175628482110430
Author(s):  
Hee Seung Hong ◽  
Kyuwon Kim ◽  
Kyunghwan Oh ◽  
Jae Yong Lee ◽  
Seung Wook Hong ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Oral Administration ◽  
Clinical Response ◽  
Activity Index ◽  
Medical Center ◽  
Retrospective Chart Review ◽  
Asian Population ◽  
Aminosalicylic Acid ◽  
Parenteral Injection

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn’s disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn’s disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX ( p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration.

scholarly journals Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn’s disease

2002 ◽  
Vol 61 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Miranda C. E. Lomer ◽  
Richard P. H. Thompson ◽  
Jonathan J. Powell
Keyword(s):  
Crohn’S Disease ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Ultrafine Particles ◽  
Activity Index ◽  
Food Additives ◽  
Disease Activity Index ◽  
Mucosal Immune Response ◽  
Double Blind

Crohn’s disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0·1–1·0 µm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn’s disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 1012 particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn’s disease, with a significant (P = 0·002) improvement in the Crohn’s disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.

scholarly journals Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn’s disease

2019 ◽  
Vol 12 ◽  
pp. 175628481988073
Author(s):  
Xiao-Xian Qian ◽  
Chen-Wen Cai ◽  
Han-Yang Li ◽  
Li-Jie Lai ◽  
Dong-Juan Song ◽  
...  
Keyword(s):  
Body Weight ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Intestinal Permeability ◽  
Activity Index ◽  
Trinitrobenzene Sulfonic Acid ◽  
T84 Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Objectives: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn’s disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. Methods: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. Results: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI ( r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI ( r = 0.824, p = 0.008), HI ( r = 0.672, p = 0.021), and intestinal permeability ( r = 0.636, p = 0.012), while negatively correlated with body weight ( r = –0.574, p = 0.035), colon length ( r = –0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. Conclusions: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.

scholarly journals Oral 5-Aminosalicyclic Acid Versus 6-Methylprednisolone in Active Crohn's Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 446-451 ◽  
Author(s):  
Jürgen Schölmerich ◽  
Harro Jenss ◽  
Franz Hartmann ◽  
Hanne Döpfer ◽  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Entrance Examination ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Treatment Groups ◽  
Starting Dose

The response to 5-aminosalicylic acid (5-ASA) in active Crohn's disease was studied in comparison to methylprednisolone in a 24 week randomized double-blind multicentre study. Sixty-two patients were included in the analysis. Thirty were treated with 500 mg 5-ASA qid and 32 with methylprednisolone (starting dose 48 mg for one week, then reduced weekly to 32, 24, 20, 16 and 12 mg with maintenance at 8 mg/day for the remaining 18 weeks). Mean age, earlier surgical intervention, localization of Crohn's disease and extraintestinal manifestations were not different in both groups. The Crohn's disease activity index (CDAI) and the van Hees index were not significantly different in both treatment groups at the entrance examination (median CDAI 232 in the 5-ASA group and 220 in the methylprednisolone group). According to the protocol, treatment was stopped due to insufficient efficacy in 73% of the patients receiving 5-ASA and in 34% of the patients receiving methylprednisolone (x2test P=0.0019). The area under the curve for the CDAl was significantly greater in 5-ASA (median 170) than in methylprednisolone (P≤0.007) (68). Eleven per cent of patients taking 5-ASA and 26% of patients taking methylprednisolone presented relevant side effects to treatment (not significant). It is concluded from these data that 5-ASA at the dose used in this study is not efficient in the treatment of active Crohn's disease. Considering recent studies in ulcerative colitis, a trial using a higher dose is indicated.

Crohn’s disease

2018 ◽  
Vol 11 (8) ◽  
pp. 435-442
Author(s):  
James Franklin
Keyword(s):  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Crohn’S Disease ◽  
Abdominal Pain ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Terminal Ileum ◽  
Bowel Disease ◽  
Rare Condition ◽  
Inflammatory Bowel

Crohn’s disease is a chronic relapsing gastrointestinal condition. It is an inflammatory bowel disease that can affect any part of the gastrointestinal tract from mouth to anus, but most commonly affects the terminal ileum and colon. Individuals can present with a wide variety of symptoms, but diarrhoea, abdominal pain and weight loss are the most common. It is a rare condition, but GPs play an important role in recognising Crohn’s disease and supporting patients through their lifelong treatment.

scholarly journals Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn’s Disease

2019 ◽  
Author(s):  
James D Lewis ◽  
Paul Rutgeerts ◽  
Brian G Feagan ◽  
Geert D’haens ◽  
Silvio Danese ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Abdominal Pain ◽  
Crohn's Disease ◽  
Linear Regression ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Stool Frequency ◽  
Endoscopic Score ◽  
Disease Location

Abstract Background The Crohn’s Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn’s Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship. Methods We pooled patient-level data from 3 placebo-controlled Crohn’s disease (CD) trials that tested adalimumab, upadacitinib, and risankizumab. Disease location was defined as ileum only, colon only, or ileocolonic based upon colonoscopy at study entry. Pearson correlation coefficients and linear regression assessed correlations between items of the CDAI and SES-CD. Results A total of 353 patients were included (20.7% ileal, 30.6% colonic, 48.7% ileocolonic disease). Crohn’s Disease Activity Index and SES-CD scores were moderately correlated (R = 0.33; P < 0.001). Among CDAI items, the strongest correlations with SES-CD were seen with very soft or liquid stool frequency (SF) and patient-reported outcome 2 (PRO2; which includes SF and abdominal pain score; both R = 0.36; P < 0.001); these correlations were numerically stronger in colonic disease (SF: R = 0.46; P < 0.001; PRO2: R = 0.44; P < 0.001) than in ileal disease (SF: R = 0.14; P = 0.23; PRO2: R = 0.21; P = 0.07), although a test for interaction was not significant. In adjusted linear regression models, the proportion of mucosa that was inflamed and the proportion of mucosa with ulceration were positively correlated, whereas the presence of strictures was inversely correlated with SF. Conclusions The SF item of the CDAI is moderately correlated with SES-CD and independently correlated with mucosal ulceration, inflammation, and strictures. Understanding why bowel inflammation as measured endoscopically does not correlate more strongly with patients’ symptoms could help develop scales that link CD pathology to patient experience.

scholarly journals Refractory Crohn’s Disease of the Vulva Treated with Infliximab: A Case Report

2007 ◽  
Vol 21 (12) ◽  
pp. 835-837 ◽  
Author(s):  
Sapna Makhija ◽  
Martin Trotter ◽  
Elizabeth Wagner ◽  
Sylvain Coderre ◽  
Remo Panaccione
Keyword(s):  
Weight Loss ◽  
Crohn’S Disease ◽  
Abdominal Pain ◽  
Case Report ◽  
Crohn's Disease ◽  
Inflammatory Disorder ◽  
Extraintestinal Manifestations ◽  
Common Presentation ◽  
The Common ◽  
Systemic Symptoms

Crohn’s disease (CD) is a chronic relapsing and remitting inflammatory disorder of the gastrointestinal tract. The common presentation includes abdominal pain, abdominal cramping and diarrhea. Many patients may exhibit systemic symptoms of fever and weight loss. Approximately 20% to 40% of patients will experience extraintestinal manifestations that involve the eyes, skin and joints. Women may experience a variety of gynecological manifestations, including vulvovaginal involvement, which is often not recognized and also difficult to treat. A case of refractory vulvovaginal CD is presented and the literature of gynecological manifestations of CD and its treatment are reviewed.

Efficacy of tumor necrosis factor-alpha inhibitors in fistulising perianal Crohn’s disease

2013 ◽  
Vol 154 (49) ◽  
pp. 1943-1948 ◽  
Author(s):  
Renáta Bor ◽  
Klaudia Farkas ◽  
Anita Bálint ◽  
Mónika Szűcs ◽  
Szabolcs Ábrahám ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Tumor Necrosis Factor ◽  
Crohn's Disease ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Activity Index ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
One Year ◽  
Necrosis Factor

Introduction: Tumor necrosis factor-alpha inhibitors are increasingly used in the treatment of severe Crohn’s disease. Aim: The aim of the authors was to assess retrospectively the short and long term efficacy of tumor necrosis factor-alpha inhibitors in fistulising Crohn’s disease. Method: Responses to therapy was determined using Crohn’s Disease Activity Index, Perianal Disease Activity Index, the rate of complete fistula closure and the additional surgical procedures during biological therapy. Results: After 12 weeks the perianal activity was decreased in more than 80% of the cases, and the complete remission rate was about 60%. After one year of therapy about one third of the patients had fistula closure, but after cessation of the biological therapy recurrence of fistulas was detected in every second patient. In most cases additional immunosuppressive therapy was necessary during biological treatment. During the one-year therapy period additional surgical treatments were performed in 45% of patients; seton insertion and abscess drainage were the most frequent procedures. Conclusions: Tumor necrosis factor-alpha inhibitor therapy is effective in the treatment of perianal Crohn’s disease, however, additional immunosuppressive drugs and rectum sparing surgical procedures were necessary during the one-year treatment period. Because of the high rate of fistula recurrence, long term tumor necrosis factor-alpha treatment may be useful. Orv. Hetil., 154(49), 1943–1948.

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