Alexandra Gutierrez

Long‐term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7‐year results from the PRECiSE 3 study

The efficacy and safety of certolizumab pegol (CZP) in moderate‐to‐severe Crohns disease were demonstrated in two 26‐week double‐blind studies (PRECiSE 1 & 2).

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice

BACKGROUND AND AIMS Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohns disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. METHODS Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. RESULTS One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohns Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. CONCLUSIONS Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort.

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study

Clinical factors were previously identified as predictors of short‐term treatment efficacy in Crohns disease (CD). The PRECiSE 3 (P3) 7‐year trial provides an opportunity to study predictors of short‐ and long‐term clinical remission among CD patients treated with certolizumab pegol (CZP).

Autoimmune Hepatitis-Primary Sclerosing Cholangitis Overlap Syndrome Complicated by Crohn’s Disease

transhepatic cholangiography (PTC) with temporary biliary stenting was performed within a month of the new diagnosis for worsening cholestasis. Three months later, mycophenolate mofetil (Cellcept) was started for persistently increased transaminases. She finally began to respond with significant decrease in serum transaminase and alkaline phosphatase levels. After 3 years of successful management, she developed diarrhea and abdominal cramping. Colonoscopy revealed extensive patchy mucosal inflammation throughout the colon and terminal ileum. Mucosal biopsies demonstrated extensive crypt distortion, focal cryptitis, increased chronic inflammation, fibrino-inflammatory exudates and erosion establishing a diagnosis of Crohn’s disease (CD) ( fig. 1 ). Contrasted CT scan of the abdomen and pelvis revealed diffuse thickening of terminal ileum, cecum, ascending and transverse colonic wall and pericolic stranding consistent with active inflammatory bowel disease. It also demonstrated signs of liver cirrhosis (based on the increased caudate to right lobe ratio) as well as intraand extrahepatic biliary dilation ( fig. 2 a, b). Budesonide 9 mg daily was added to treat active CD and prednisone was discontinued. She remained symptomatic with continued diarrhea and further deterioraDear Sir Autoimmune hepatitis-primary sclerosing cholangitis (AIH-PSC) overlap syndrome is characterized by features of both conditions. Association of AIH-PSC overlap syndrome with ulcerative colitis (UC) is well recognized but is rarely seen with Crohn’s disease (CD). We report a case of a young African-American woman with AIH-PSC overlap syndrome complicated by CD that illustrates the approach to diagnosis and management of the condition. A brief discussion of the topic follows the case presentation.

Reinduction with Certolizumab Pegol in Patients with Crohn's Disease Experiencing Disease Exacerbation: 7-year Data from the Precise 4 Study

Background:Patients with Crohns disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2. Methods:Patients eligible for PRECiSE 4 had Crohns disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy. Results:Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohns disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient-years was 6.11 for serious infections and 1.29 for malignancies. Conclusions:Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings.

Crohn's colitis with perianal disease complicated by collagenous colitis: discourse on management options.

disease. She also had a history of depression and had undergone trials of several mood stabilizers over the years. The patient was being maintained in clinical remission on a TNF blocker when she developed new onset perianal pain with discharge as well as increased diarrhea for which endoscopic and surgical evaluation was scheduled. An active perianal fistula was confirmed with a probe ( fig. 1 ). Flexible sigmoidoscopy performed after seton placement into the fistula revealed a completely normal colonic mucosa to the level of the splenic flexure except for a minute area of inflammation at the anorectal junction where biopsies were taken. The pathology report suggested evidence of subepithelial accentuation of collagen band with increased chronic inflammation ( fig. 2 a, b). A subsequent colonoscopy performed for complete colonic mucosal evaluation also did not reveal any endoscopic disease, however, random colonic biopsies taken during the procedure confirmed the subepithelial accentuation of collagen band with increased chronic inflammation throughout the colon, therefore establishing a diagnosis of concomitant CC in the patient ( fig. 3 ). The patient had a history of severe acute steroid psychosis in the past and Dear Sir, Crohn’s disease (CD) and collagenous colitis (CC) are rarely seen together in clinical practice and when they are, they may present a management challenge. We describe the case of a patient with perianal CD unable to take steroids whose clinical course was complicated by the development of CC. A brief review of the topic follows the case presentation.

Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol: Longitudinal Data from a 7-Year Study in Crohn's Disease

Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohns disease. Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP–ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP–ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Results: Of the CZP–ADAb–positive patients, 40 (22.6%) had transient CZP–ADAbs and 94 (77.4%) had persistent CZP–ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP–ADAb–positive group relative to the CZP–ADAb–negative group. Transient CZP–ADAb–positive and CZP–ADAb–negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. Conclusions: This analysis demonstrates that persistent CZP–ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery

Abstract Background Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence. Methods Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968. Demographic and clinical data were obtained from medical records. Wilcoxon, ANOVA, Chi square, and Fisher’s exact tests were used for comparisons. Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking. Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery. (Significance: P < 0.05 for main effects; P < 0.2 for interaction terms) Results 400 (65.8%) patients had Crohn’s disease (CD) and 208 (34.2%) had ulcerative colitis (UC). 298 (49%) underwent an IBD-related surgery. There was a trend towards significance between rs16969968 and smoking behavior (smoking status [P = 0.05], nicotine dependence [AA > AG > GG; P = 0.08]). Smoking and genotype were not independently associated with surgery in UC or CD. However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1). CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD. The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery.

Smoking Interacts with CHRNA5, a Nicotine Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD Related Surgery

Background Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence. Methods Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968. Demographic and clinical data were obtained from medical records. Wilcoxon, ANOVA, Chi square, and Fishers exact tests were used for comparisons. Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking. Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery. (Significance: P AG > GG; P = 0.08]). Smoking and genotype were not independently associated with surgery in UC or CD. However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1). CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD. The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery. 10.1093/ibd/izx094_video1izx094.video15775248538001.

Considerations in Imaging Among Emergency Department Patients With Inflammatory Bowel Disease

&NA; Patients with inflammatory bowel disease who experience abdominal pain and gastrointestinal symptoms often seek care in the emergency department (ED). These patients commonly undergo abdominopelvic computed tomography (CT) as part of their evaluation, and the rate of imaging appears to be increasing without a corresponding increase in identification of clinically actionable findings or effect on disposition. Studies demonstrate that the yield of CT tends to be fairly high. Yet, because inflammatory bowel disease is often diagnosed at an early age, these patients are repeatedly imaged during their lifetime, a subset of whom accumulate high levels of ionizing radiation exposure, increasing their risk of cancer. This compounds an already increased risk of cancer in these patients because of inflammatory bowel disease alone. Lack of intimate knowledge of a patient’s disease phenotype and disease progression contributes to uncertainty in distinguishing between an inflammatory exacerbation; a complication such as obstruction, abscess, perforation, fistula, or stricture; and a noninflammatory‐bowel‐disease‐related condition. This uncertainty can lead to overuse of imaging with CT. Limited availability of and lack of awareness of alternate imaging modalities and strategies may prevent providers from pursuing strategies that avoid ionizing radiation. In this article, we review options for imaging inflammatory bowel disease patients in the ED and attempts undertaken to risk stratify these patients, and we discuss ways in which details of a patient’s disease might guide imaging decisionmaking.