Abstract Background Subjects maintained on infliximab scheduled therapy for inflammatory bowel disease may require dose optimization due to secondary loss of response. There are limited data on ...infliximab dose optimization for ulcerative colitis. Aims To investigate dose optimization in ulcerative colitis patients with secondary loss of response. Methods This was a retrospective multicentre study. Primary outcome was rapid clinical response assessed at the next administration of infliximab after dose intensification. Secondary outcomes were rapid clinical remission, and clinical response, remission and colectomy rate by week 52. Doubling the dose (10 mg/kg q8 weeks) vs. shortening the dose interval (5 mg/kg every 6 or 4 weeks) were compared. Results Forty-one patients from eight centres were enrolled (15 for double dose and 26 for interval shortening). Rapid response was achieved in 37/41 patients (90.2%), while 19/41 (46.3%) achieved rapid clinical remission. At week 52, 28/41 patients were maintained in clinical remission, but 4 (9.8%) underwent colectomy. No difference was found between the two optimization strategies. Subjects achieving rapid clinical response had a significantly higher colectomy-free rate at week 52 ( p = 0.002). Conclusion Dose optimization of infliximab was effective to restore clinical response or remission and to prevent colectomy in ulcerative colitis patients with secondary loss of response.
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal ...lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathology. Remission, is usually defined as resolution of symptoms. Recently, mucosal healing (MH) has emerged as an important end point of any short-term medical therapy for IBD. It may predict long-term remission and may impact on the natural history of the disease in Crohn's disease (CD), while data in UC patients are still limited. This review of the literature is focused on the recent evidence on the impact of medications on MH in UC and on the impact of MH on the natural course of UC.
Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific ...microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD. Conventional therapy of UC quite commonly fails to avoid complications or colectomy and the therapeutic armamentarium remains still limited. New therapeutic options, such as, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucoapheresis, have been investigated recently. Biological therapy is focused on different targets involved in the inflammatory process. Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNF-α agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and more. We review the recent advances in biological therapy for UC treatment beyond the anti-TNFs.
Ulcerative colitis (UC) is a chronic inflammatory disease rarely arising during gestation. Because the available information is based on case reports or small retrospective studies, diagnosis may be ...difficult and treatment is still controversial. A case of toxic megacolon developing in late pregnancy associated to a sudden fetal decompensation is described. Diagnostic and clinical topics of acute UC onset in pregnancy are debated.A primipara, 34 years old, 33/0 weeks of gestation, was admitted with a diagnosis of preterm labor, associated to acute bloody diarrhea (up to 10 daily motions) and cramping abdominal pain. A diagnosis of new‐onset early‐stage UC was made by sigmoidoscopy. An intensive care regimen including hydrocortisone, antibiotics and parenteral nutrition was immediately started. Magnetic resonance imaging of maternal abdomen, fostered by the worsening patient conditions, evidenced dilatation of the entire colon and a severely hampered of fetal muscular tone.Toxic megacolon complicated by superimposed Clostridium difficile infection was associated to a sudden fetal decompensation diagnosed by chance during maternal abdominal magnetic resonance imaging. An emergency cesarean section was mandatory. According to a senior surgeon's decision, total colectomy was not immediately performed following cesarean section with reference to the absence of colonic perforation. We obtained a good short‐term maternal outcome and an uncomplicated neonatal course. Counseling of those patients must be focused on timely and multidisciplinary intervention in order to improve the course of maternal disease and to prevent fetal distress.
The advent of salicylates in the treatment of ulcerative colitis started in 1938 with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the first time a therapeutic chance to ...patients with ulcerative colitis. In this paper we describe the fascinating history of Salazopyrin and salicylates from the first serendipitous observations to the last randomized clinical trials. Attention was paid to the pharmacokinetics and the mechanism of action of 5-aminosalicylates and, in particular, to the issue of the mucosal concentrations of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new oral mesalazine formulations that allow the homogenous distribution of 5-aminosalicylate through all the large bowel was taken. Lastly, the possible use of mesalazine in the prevention of colorectal cancer was reviewed.
Small intestinal bacterial overgrowth (SIBO) has been reported with varying prevalence, depending upon the criteria used for diagnosis. Lactulose and glucose breath tests are the most used in ...clinical settings. Early rises of hydrogen excretion during a lactose breath test suggest SIBO, but the finding could result from accelerated mouth-to-caecum transit time.
Defining the prevalence of early hydrogen peaks during lactose breath tests and assessing the proportion of patients affected by SIBO.
An early (≤ 60′) hydrogen excretion peak was observed in 120/663 patients with positive lactose hydrogen breath test. Eighty-one of them underwent a 50 g-9sample-glucose hydrogen breath test to diagnose SIBO.
The glucose breath test proved positive in 11/81 (13.6%) patients. The positivity rate was 18.2% (2/11) in those with the first peak detected at 30′ and 12.8% (9/70) in those with the peak occurring at 60′.
Early hydrogen excretion peaks are rarely associated with SIBO. The low positive predictive value indicates that the finding does not help identifying patients at high risk for this condition. Indirectly, the present data support the opinion that the prevalence of SIBO diagnosed by standard lactulose breath tests is much lower than reported, and the reliability of the test is low.
Background:
The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been ...correlated with outcomes.
Methods:
Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission.
Results:
Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400mg/d (median 5 days range 1–11). Median follow-up was 14 months (2–33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0–8) was 5 (3–8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 range 4–8 versus 5/8 3–8, both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint.
Conclusion:
Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin.
Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory bowel disease (IBD), both in Crohn's disease (CD) and ulcerative colitis (UC). In the last decade, some progress has ...been made in understanding their key role in leukocyte trafficking control in terms of basic research, but evidence of clinical efficacy is lacking. In the last 2 years, new molecules directed against integrins and integrin receptors have been developed and investigated in clinical trials, showing that anti-α4β7 integrin agents can be effective and safe for the induction and maintenance of remission in active CD and UC. Preliminary data show that anti-MAdCAM, anti-β7 and anti-integrin receptor agents are not all effective in IBD. Such results open new perspectives on clinical management of IBD, and new directions in understanding the role of adhesion molecules and leukocyte recruitment both in CD and UC.
Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids ...during hospitalization is superior to corticosteroids alone is unknown.
This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy.
Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07).
In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation.
gov ID: NCT01941589.
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