Background and Aims
Infliximab rescue therapy is effective in patients with corticosteroid refractory acute severe ulcerative colitis, but predictors of response remain poorly understood. We aimed to ...identify predictors of colectomy in this high-risk patient population.
Methods
Patients hospitalized with acute severe ulcerative colitis who received infliximab after failing intravenous corticosteroid therapy between July 2012 and June 2017 were retrospectively identified. Stepwise regression with backward elimination was used to identify predictors of colectomy at 90 days and 1 year. Ninety-day and 1-year colectomy rates were compared between the patients who received 5 mg/kg and 10 mg/kg IFX rescue dose.
Results
Sixty-three patients met the eligibility criteria. Twenty-nine patients received 5 mg/kg, and 34 received 10 mg/kg infliximab dose. Serum albumin on admission (OR 0.10;
p
= 0.04) and band neutrophil percentage at the time of infliximab administration (OR 1.21;
p
= 0.02) were independent predictors of 90-day colectomy. A combination of serum albumin ≤ 2.5 g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy. Unadjusted 90-day and 1-year colectomy rates were similar in the 5 mg/kg and 10 mg/kg infliximab groups. After adjusting for confounding factors, 10 mg/kg infliximab dose was potentially protective for 90-day (OR 0.07;
p
= 0.06) but not for 1-year colectomy (OR 0.19;
p
= 0.16).
Conclusions
Bandemia and low serum albumin are independent predictors of failure of infliximab rescue therapy in acute severe ulcerative colitis. Serum albumin ≤ 2.5 g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy.
Background & Aims
: Crohn’s disease patients can be characterized by antibody responses against Crohn’s disease-related bacterial sequence,
Escherichia coli outer membrane porin C,
Saccharomyces ...cerevisiae (oligomannan), and neutrophil nuclear antigens. Our aim was to determine whether expression of antibodies against Crohn’s disease-related bacterial sequence and
Escherichia coli outer membrane porin C is associated with distinct phenotypic manifestations.
Methods
: Sera from 303 patients were tested for antibodies to the Crohn’s disease-related bacterial sequence (I2), anti-
Escherichia coli outer membrane porin C, anti-
Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibodies and for 3 Crohn’s disease-associated variants of the NOD2 gene (R702W, G908R, and 1007fs) and compared with clinical data.
Results
: Patients expressing I2 were more likely to have fibrostenosing Crohn’s disease (64.4% vs. 40.7%;
P < 0.001) and to require small bowel surgery (62.2% vs. 37.4%;
P < 0.001). Patients with anti-
Escherichia coli outer membrane porin C were more likely to have internal perforating disease (50.0% vs. 30.7%;
P = 0.001) and to require small bowel surgery (61.4% vs. 44.2%;
P = 0.003). Anti-Crohn’s disease-related bacterial sequence was independently associated with fibrostenosis (
P = 0.027) and small bowel surgery (
P = 0.01), whereas anti-
Escherichia coli outer membrane porin C was independently associated with internal perforations (
P < 0.006). Patients positive for I2, anti-
Escherichia coli outer membrane porin C, and anti-
Saccharomyces cerevisiae were the most likely to have undergone small bowel surgery (72.0%; odds ratio, 8.6;
P < 0.001) compared with patients without reactivity (23.0%). When the presence and magnitude of antibody responses were considered, 90% of patients with small bowel disease who required surgery had high levels of I2,
Escherichia coli outer membrane porin C, and oligomannan antibodies, compared with only 18.2% with low-titer responses (
P < 0.001).
Conclusions
: I2 and anti-
Escherichia coli outer membrane porin C are associated with Crohn’s disease phenotypes, and patients with the highest level of serum reactivity toward an increasing number of microbiota have the greatest frequency of strictures, internal perforations, and small bowel surgery.
Background & Aims:
Control of Crohn’s disease (CD) is important for conception and sustaining a pregnancy to term. Small series of infliximab use during pregnancy have reported favorable fetal and ...maternal outcomes. As a result of heightened maternal concern triggered by recent labeling changes, infliximab levels were measured in the newborn of a mother treated with infliximab.
Methods:
Serum and breast milk infliximab levels were measured by enzyme-linked immunosorbent assay.
Results:
A 32-year-old woman with treatment-refractory CD continued infliximab therapy throughout pregnancy. Five infusions of infliximab, 10 mg/kg, the last one 2 weeks before delivery, successfully controlled her symptoms. Six weeks after delivery, the breast-fed infant’s serum infliximab level was 39.5 μg/mL. Infliximab was not detected in the breast milk. Serial measurements revealed a continued slow decline of the infant’s infliximab levels during the following 6 months, despite resumption of breast-feeding and subsequent retreatments of the mother with infliximab.
Conclusions:
Clinically significant infliximab levels were detected in the offspring. High infliximab levels in the serum of this infant are likely due to placental transfer, not breast-feeding. Similar to other maternally acquired antibodies, the half-life of infliximab appears prolonged in newborns. The true short-term and long-term implications of exposure to infliximab during the newborn period are unknown. Patients and physicians must be informed about in utero exposure to infliximab and potentially other therapeutic antibodies. The timing of infusions to minimize antibody transfer to the fetus might be an important strategic consideration when therapeutic antibodies are used in pregnancy.
Background:
Acute severe ulcerative colitis (UC) remains a significant clinical challenge and the ability to predict, at an early stage, those individuals at risk of colectomy for medically ...refractory UC (MR‐UC) would be a major clinical advance. The aim of this study was to use a genome‐wide association study (GWAS) in a well‐characterized cohort of UC patients to identify genetic variation that contributes to MR‐UC.
Methods:
A GWAS comparing 324 MR‐UC patients with 537 non‐MR‐UC patients was analyzed using logistic regression and Cox proportional hazards methods. In addition, the MR‐UC patients were compared with 2601 healthy controls.
Results:
MR‐UC was associated with more extensive disease (P = 2.7 × 10−6) and a positive family history of UC (P = 0.004). A risk score based on the combination of 46 single nucleotide polymorphisms (SNPs) associated with MR‐UC explained 48% of the variance for colectomy risk in our cohort. Risk scores divided into quarters showed the risk of colectomy to be 0%, 17%, 74%, and 100% in the four groups. Comparison of the MR‐UC subjects with healthy controls confirmed the contribution of the major histocompatibility complex to severe UC (peak association: rs17207986, P = 1.4 × 10−16) and provided genome‐wide suggestive association at the TNFSF15 (TL1A) locus (peak association: rs11554257, P = 1.4 × 10−6).
Conclusions:
A SNP‐based risk scoring system, identified here by GWAS analyses, may provide a useful adjunct to clinical parameters for predicting the natural history of UC. Furthermore, discovery of genetic processes underlying disease severity may help to identify pathways for novel therapeutic intervention in severe UC. (Inflamm Bowel Dis 2010)
The treatment of inflammatory bowel disease (IBD) often includes immunosuppressive medications, which may increase the risk of vaccine-preventable illnesses. We aimed to assess the impact of ...immunosuppression on immune responses to pneumococcal vaccination in patients with IBD.
The study design consists of a prospective controlled clinical trial. This study was carried out at a tertiary-care IBD clinic. The subjects for the study belonged to one of the following three groups: adult patients with IBD on combination TNF-blockers and immunomodulators (Group A), those without immunosuppressive therapy (Group B), and age-matched healthy controls (Group C). The treatment consisted of immunization with 23-valent pneumococcal polysaccharide vaccines (PSVs). The main outcome was immune response for five serotypes defined as a twofold or greater increase from pre-vaccination titers and > or =1 microg post-vaccination titer.
Sixty-four subjects participated in the study: 20 in Group A, 25 in Group B, and 19 in Group C. Pre-vaccination titers were similar among the three groups. Vaccine responses were lower in Group A than in Group B (P< or =0.01 for four out of five antigens) and Group C (P<0.01 for all five antigens). Overall vaccine response was seen in 45, 80, and 85% of Groups A, B, and C (P=0.01), respectively.
Immune response to PSV-23 is impaired in Crohn's disease (CD) patients on combination immunosuppressive therapy but is normal among non-immunosuppressed patients. Given the unpredictable likelihood for immunosuppressive therapy, newly diagnosed patients with IBD should undergo vaccination before the initiation of immunosuppressive therapy.
Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive therapies, potentially increasing their risk of ...developing an infection. Empiric data suggest that vaccines are underutilized in immunocompromised patients, despite published guidelines recommending their use. We aimed to assess exposure risk and immunization status among patients receiving care in an IBD specialty clinic.
Patients completed a self-administered, pretested, structured questionnaire during a routine visit for the management of IBD. Survey questions related to medical and immunization histories, and exposures to known risk factors for influenza, pneumococcus, viral hepatitis, and varicella. Additionally, in a subgroup of patients who agreed to donate a sample of blood, immune status to hepatitis A (HAV), hepatitis B (HBV), and varicella was determined.
Two hundred four patients were asked to participate in the study; 169 completed surveys and comprised the study population. Mean age was 35 yr (range 13-75 yr). One hundred forty-six respondents (86%) reported current or prior use of immunosuppressive medications. Only 45% of respondents recalled tetanus immunization within the past 10 yr, 41 (28%) reported regularly receiving flu shots, and 13 (9%) reported having received pneumococcal vaccine. The most common reasons for nonimmunization with influenza included lack of awareness (49%) and concern for side effects (18%). Responses indicated that 75 (44%) patients were at risk for HBV but only 47 (28%) had been vaccinated against the infection; of patients with previous HBV vaccination, only three of nine (33%) had measurable antibodies against hepatitis B surface antigen.
Immunization against selected vaccine-preventable illnesses was uncommon in patients with IBD, despite the presence of significant risk factors. Efforts to improve immunization status among patients with IBD and other chronic, immune-mediated conditions are needed.
Abstract
Background
Crohn disease (CD) affects the small bowel in 80% of patients. Double balloon endoscopy (DBE) provides the potential for direct and extensive mucosal visualization with the ...potential for diagnostic monitoring and therapeutic intervention. This study aimed to investigate the safety and effectiveness of DBE in small-bowel CD.
Methods
From our DBE database, patients with CD at the time of index DBE (January 2004-January 2013) were identified. Data collection included demographics, CD phenotype (age at diagnosis, disease location, disease activity), procedural information, adverse events (perforation, pancreatitis, death), therapeutic intervention (stricture dilation), and outcome (escalation or maintenance of existing therapy, referral to surgery).
Results
A total of 184 DBEs were performed in patients with inflammatory bowel disease over 162 endoscopic sessions. In this cohort, 115 patients had previously diagnosed CD. A diagnosis of CD was made in 22 patients. Of those with known CD, 140 DBEs were performed in 82 patients; DBE findings led to escalation of medical therapy in 26% of patients, maintenance of therapy in 26% of patients, and surgery in 18% of patients. We considered DBE to have failed in 11% (n = 18) of patients. During 46 endoscopic sessions, in 29 patients, 103 strictures were dilated via balloon dilation. Of patients undergoing dilation with clinical follow-up, 19 of 24 (79%) patients were surgery-free during the study period. Overall, there were 2 perforations.
Conclusions
We found that DBE is a safe and effective procedure in patients with suspected or established CD. Furthermore, patients undergoing dilation of strictures via DBE had an 80% surgery-free rate within the follow-up period.
Crohn's disease (CD) is considered a contraindication to ileal pouch--anal anastomosis (IPAA). In this study, we compare outcomes of CD and ulcerative colitis (UC) patients undergoing IPAA.
Patients ...were considered to have CD before surgery based on a history of small bowel disease, perianal disease, noncrypt-associated granuloma, or pretreatment skip colonic lesions. Patients were prospectively assessed for pouchitis or CD. Postoperative CD (pouch inflammation into the afferent limb or pouch fistula) or pouch failure (need for permanent diversion) were assessed. Preoperative serum was assayed for IBD-associated antibodies using enzyme-linked immunosorbent assay (ELISA).
Seventeen patients with preoperative CD were identified. Seven (41%) patients developed postoperative recurrent CD in the afferent limb (n = 3) or pouch fistulizing disease (n = 4). One patient (6%) required pouch excision. The incidence of postoperative CD was higher (P = 0.002) in preoperative CD patients (41%) than UC patients (11%). There was no significant difference in pouchitis or pouch failure. There was also no significant difference in any preoperative clinical feature between patients with or without postoperative CD. Afferent limb inflammation developed in three (50%) of the six patients with pANCA+/OmpC- expression compared to none of the 11 patients without this serologic profile (P = 0.03).
Although the intentional use of IPAA in CD has a higher incidence of postoperative disease vs. UC patients, there was no significant difference in pouch failure. Demographics, clinical features, and serologic factors do not predict outcome of CD patients undergoing IPAA. IBD serology may identify the phenotype manifestation of postoperative recurrent CD.
Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased ...readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P=0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P<0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P=0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% P=0.04; length of stay, 13.62 days versus 6.38 days P=0.02). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.
Background & Aims The ability to identify children with CD who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. ...The aims of this study were to determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression. Methods Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti–outer membrane protein C, anti– Saccharomyces cerevisiae , and perinuclear antineutrophil cytoplasmic antibody by using enzyme-linked immunosorbent assay. Genotyping (Taqman MGB) was performed for 3 CARD15 variants (single nucleotide polymorphisms 8, 12, and 13). Associations between immune responses (antibody sum and quartile sum score, CARD15, and clinical phenotype were evaluated. Results Thirty-two percent of patients developed at least 1 disease complication within a median of 32 months, and 18% underwent surgery. The frequency of internal penetrating, stricturing, and surgery significantly increased ( P trend < .0001 for all 3 outcomes) with increasing antibody sum and quartile sum score. Nine percent of seropositive groups had internal penetrating/stricturing versus 2.9% in the seronegative group ( P = .01). Twelve percent of seropositive groups underwent surgery versus 2% in the seronegative group ( P = .0001). The highest antibody sum group (3) and quartile sum score group (4) demonstrated the most rapid disease progression ( P < .0001). Increased hazard ratio was observed for antibody sum group 3 (7.8; confidence interval, 2.2–28.7), P < .002 and quartile sum score group 4 (11.0; confidence interval, 1.5–83.0, P < .02). Conclusions The rate of complicated CD increases in children as the number and magnitude of immune reactivity increase. Disease progression is significantly faster in children expressing immune reactivity.
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