Gut. 2015 May 2. pii: gutjnl-2014-308973.
Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease.
Khanna R, Zou G, D'Haens G, et al.
OBJECTIVE: The Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however, neither instrument has been fully validated. We assessed intra-rater and inter-rater reliability of these indices.
DESIGN: Video recordings of colonoscopies obtained from 50 patients with CD who participated in an induction trial of a biological therapy were triplicated and reviewed in random order by four central readers. Data were used to assess intra-rater and inter-rater reliability for CDEIS, SES-CD and a global evaluation of lesion severity (GELS). Subsequently, readers participated in a consensus process that identified common sources of disagreement.
RESULTS: Intraclass correlation coefficients (ICCs) for intra-rater reliability for CDEIS, SES-CD and GELS (95% CIs) were 0.89 (0.86 to 0.93), 0.91 (0.89 to 0.95) and 0.81 (0.77 to 0.89), respectively, with standard error of measurement (SEM) of 2.10, 2.42 and 1.15. The corresponding ICCs for inter-rater reliability were 0.71 (0.63 to 0.76), 0.83 (0.75 to 0.88) and 0.62 (0.52 to 0.70), with SEM of 3.42, 3.07 and 1.63, respectively. Correlation between CDEIS and GELS was 0.75, between SES-CD and GELS was 0.74 and between CDEIS and SES-CD was 0.92. The most common sources of disagreement were interpretation of superficial ulceration, definition of disease site at the ileocolonic anastomosis, assessment of anorectal lesions and grading severity of stenosis.
CONCLUSIONS: Central reading of CDEIS and SES-CD had 'substantial' to 'almost perfect' intra-rater and inter-rater reliability; however, the responsiveness of these instruments is yet to be determined.
Am J Gastroenterol. 2015 May 12.
C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis.
Mosli MH, Zou G, Garg SK, et al.
OBJECTIVES: Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate thediagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD.
METHODS: Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.
RESULTS: Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease.
CONCLUSIONS: Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.
Crohns Colitis. 2015 May 9. pii: jjv080.
Bowel damage as assessed by the Lémann Index is reversible on anti-TNF therapy for Crohn's disease.
Fiorino G, Bonifacio C, Allocca M, et al.
BACKGROUND AND AIMS: Bowel damage (BD) will develop in about 50% of Crohn's disease (CD) patients. Recently, the Lémann Index (LI) was developed to measure BD.
METHODS: This was a prospective single-center cohort study. All included patients underwent full evaluation for bowel damage before starting anti-TNF therapy and every year thereafter. BD at baseline and during follow-up was measured using the LI. We assessed the impact of anti-TNF therapy on BD. We also assessed the sensitivity to change of the LI and the relationship between BD progression and disease outcomes, including the need for surgery.
RESULTS: Thirty CD patients were enrolled (13 on infliximab, 17 on adalimumab). Median baseline LI was 9.1 (range, 1.6-34.1). Median follow up was 32.5 months (range, 10-64). By a ROC curve analysis, a LI >4.8 defined CD subjects with BD. Any change >0.3 in the LI was related to BD change (AUC 0.98). During follow-up, 83% of subjects had BD regression and 17% had BD progression. Anti-TNF therapy significantly reduced LI at 12 months (p=0.007). Subjects with BD progression were more likely to undergo major abdominal surgery through the follow-up period (HR 0.19, p=0.005).
CONCLUSION: The LI has good sensitivity to change. Anti-TNFs agents are able to reverse BD in some CD patients. BD progression as measured by the LI may be predictive of major abdominal surgery in these patients
Inflamm Bowel Dis. 2015 May 5. [Epub ahead of print]
Previous cancer in a patient with Crohn's disease: is it appropriate to use biologics and immunosuppressants for IBD treatment?
Le PN, Greer JB, Oikonomou I, et al.
No abstract available
Eur J ClinPharmacol. 2015 May 27. [Epub ahead of print]
Review article: The pharmacokinetics and pharmacodynamics of drugs used in inflammatory bowel disease treatment.
Quetglas EG, Armuzzi A, Wigge S, et al.
BACKGROUND: The following review is a compilation of the recent advances and knowledge on the behaviour of the most frequently used compounds to treat inflammatory bowel disease in an organism.
RESULTS: It considers clinical aspects of each entity and the pharmacokinetic/pharmacodynamic relationship supported by the use of plasma monitoring, tissue concentrations, and certain aspects derived from pharmacogenetics.
J ClinGastroenterol. 2015 May 6. [Epub ahead of print]
Experience with anti-TNF-α biologic agents in succession in patients with Crohn's disease: a retrospective analysis of a single center.
Ferges W, Rampertab SD, Shafqet M, et al.
GOALS: Our aim was to identify and compare the effectiveness of antitumor necrosis factor biologics when used as initial agents and when used in succession for the treatment of moderate to severe Crohn's disease (CD).
BACKGROUND: Studies directly comparing the efficacy of biologics are lacking. When one biologic loses efficacy, patients are often treated with an alternate biologic. The effectiveness of this strategy has not been thoroughly investigated.
STUDY: This is a retrospective cohort study from a database of 153 patients with CD treated with infliximab, adalimumab, or certolizumabpegol. Response rates determined by physician global assessment were compared between biologics when given as initial agents and after failure of 1 or 2 prior biologics.
RESULTS: There were no significant differences in response between infliximab (64.5%), adalimumab (60.0%), and certolizumabpegol (66.7%) when given as initial biologics. As second-line or third-line agents after prior biologic failure, there was a trend toward increased response with infliximab (83.3%) versus adalimumab (52.7%) and certolizumabpegol (59.4%); however, this did not meet statistical significance. After failure or loss of response of 2 previous biologics, use of a third biologic was still effective with a response rate of 54.2%.CONCLUSIONS: All 3 biologics have similar efficacy in the treatment of CD when given as initial agents. Infliximab has a trend toward increased response after prior biologic failure; however, this did not meet statistical significance. Even after loss of response or failure of 2 previous biologics, trial of a third alternate biologic is an effective strategy
Inflamm Bowel Dis. 2015 May 12. [Epub ahead of print]
Comparative effectiveness of nutritional and biological therapy in North American children with active Crohn's disease.
Lee D, Baldassano RN, Otley AR, et al.
BACKGROUND: Therapeutic targets in pediatric Crohn's disease include symptoms, quality of life (QOL), and mucosal healing. Although partial enteral nutrition (PEN), exclusive enteral nutritional(EEN), and anti-tumor necrosis factor alpha (anti-TNF) therapy all improve symptoms, the comparative effectiveness of these approaches to improve QOL and achieve mucosal healing has not been assessed prospectively.
METHODS: In a prospective study of children initiating PEN, EEN, or anti-TNF therapy for Crohn's disease, we compared clinical outcomes using the Pediatric Crohn's Disease Activity Index (PCDAI), QOL (IMPACT score), and mucosal healing as estimated by fecal calprotectin (FCP). PCDAI, IMPACT, FCP, and diet (prompted 24-h recall) were measured at baseline and after 8 weeks of therapy.
RESULTS: We enrolled 90 children with active Crohn's disease (PCDAI, 33.7 ±13.7; and FCP, 976 ±754), of whom 52 were treated with anti-TNF, 22 with EEN, and 16 with PEN plus ad lib diet. Clinical response (PCDAI reduction ≥15 or final PCDAI ≤10) was achieved by 64% on PEN, 88% EEN, and 84% anti-TNF (test for trend P = 0.08). FCP ≤250 μg/g was achieved with PEN in 14%, EEN 45%, and anti-TNF 62% (test for trend P = 0.001). Improvement in overall QOL was not statistically significantly different between the 3 groups (P = 0.86). However, QOL improvement was the greatest with EEN in the body image (P = 0.03) domain and with anti-TNF in the emotional domain (P = 0.04).
CONCLUSIONS: Although PEN improved clinical symptoms, EEN and anti-TNF were more effective for decreasing mucosal inflammation and improving specific aspects of QOL.
Arch Med Sci. 2015 Apr 25;11(2):353-61. Epub 2015 Apr 23.
Is faecalcalprotectin equally useful in all Crohn's disease locations? A prospective, comparative study. Stawczyk-Eder K, Eder P, Lykowska-Szuber L, et al.
INTRODUCTION: There are data suggesting that the diagnostic usefulness of faecalcalprotectin (FC) may vary depending on the Crohn's disease (CD) location. The aim of the study was to compare the diagnostic usefulness of FC in CD patients with different disease locations.
MATERIAL AND METHODS: We prospectively enrolled 120 CD patients in the study. Disease activity was assessed by using Crohn's Disease Activity Index (CDAI), biochemical markers, and endoscopic and radiographic methods. Faecalcalprotectin concentration was assessed in single stool samples by using the ELISA method.
RESULTS: Among all patients, 54 (45%) had ileocolonic CD location, 44 (36.5%) had isolated small bowel location, and 22 (18.5%) had colonic CD location. FC correlated significantly with C-reactive protein concentration and endoscopic and radiographic activity among patients with isolated small bowel CD (p = 0.03, r = 0.32; p < 0.0001, r = 0.78; p = 0.03, r = 0.35; respectively) and with C-reactive protein and endoscopic activity in isolated colonic CD (p = 0.0009, r = 0.7; p = 0.0002, r = 0.78; respectively). CDAI and inflammatory biochemical markers did not correlate with endoscopic and radiographic assessment in small bowel CD. In patients with ileocolonic CD, FC correlated significantly with endoscopy (p = 0.006, r = 0.5), radiographic assessment (p = 0.04, r = 0.3), CDAI (p = 0.0006, r = 0.5) and the majority of biochemical markers.
CONCLUSIONS: Faecalcalprotectin is a useful diagnostic marker in all CD patients. Although its usefulness in small bowel CD seems to be the lowest, it should be utilized particularly in this disease location because of the lack of other reliable, non-invasive diagnostic methods.
Gut. 2015 May 18. pii: gutjnl-2015-309598. [Epub ahead of print]
Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up.
Bryant RV, Burger DC, Delo J, et al.
BACKGROUND: Endoscopic mucosal healing is an established treatment target for UC, yet the value of achieving histological remission remains unclear.
AIMS: To evaluate histological remission compared to endoscopic mucosal healing for predicting patient outcomes in UC.
METHODS: Blinded assessment of endoscopic and histological measures of disease activity was performed on patients with established UC at baseline. Concordance and prognostic values of endoscopic mucosal healing (defined by Baron score ≤1) and histological remission (defined by Truelove and Richards' index) for predicting outcomes of corticosteroid use, hospitalisation and colectomy were determined over a median 6 years follow-up, including κ statistics and Cox regression multivariate analysis.
RESULTS: 91 patients with UC were followed up for a median 72 months (IQR 54-75 months). Overall, concordance between endoscopic and histological remission was moderate (κ=0.56, 95% CI 0.36 to 0.77); 24% patients had persistent inflammation despite endoscopic remission. Histological remission predicted corticosteroid use and acute severe colitis requiring hospitalisation over the follow-up period (HR 0.42 (0.2 to 0.9), p=0.02; HR 0.21 (0.1 to 0.7), p=0.02; respectively), whereas endoscopic mucosal healing did not (HR 0.86, 95% CI 0.5 to 1.7, p0.65; HR 0.83 95% CI 0.3 to 2.4, p0.74; respectively).
CONCLUSIONS: Histological remission is a target distinct from endoscopic mucosal healing in UC and better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalisation, over a median of 6 years of follow-up. Our findings support the inclusion of histological indices in both UC clinical trials and practice, towards a target of 'complete remission
Mayo Clin Proc. 2015 May 8. pii: S0025-6196(15)00299-2. [Epub ahead of print]
Effect of medications on risk of cancer in patients with inflammatory bowel diseases: a population-based cohort study from Olmsted County, Minnesota.
Yadav S, Singh S, Harmsen WS, et al.
OBJECTIVES: To estimate the overall risk of cancer in a population-based cohort of patients with inflammatory bowel disease (IBD) and how IBD-related medications modify this risk.
METHODS: We identified all incident cancers (excluding nonmelanoma skin cancer) after IBD diagnosis in a cohort of 839 patients diagnosed as having IBD from January 1, 1940, through December 31, 2004, in Olmsted County, Minnesota, and followed up for a median 18 years through December 31, 2011 (122 patients taking biologic agents at last follow-up). We calculated standardized incidence ratios (SIRs) with 95% CIs of all cancers and compared cancer risk in patients treated with immunomodulators (IMMs) and biologics with that of patients not exposed to these medications, using an incidence rate ratio (IRR).
RESULTS: One hundred nine patients developed 135 cancers. The 10-year cumulative probability of cancer was 3.8%. Patients with Crohn disease (SIR, 1.6; 95% CI, 1.2-2.1) but not ulcerative colitis (SIR, 1.1; 95% CI, 0.8-1.4) had an increased overall risk of cancer compared with the general population. Patients treated with IMMs (relative to IMM-naive patients) had an increased risk of melanoma (IRR, 5.3; 95% CI, 1.1-24.8) (and a numerically higher risk of hematologic malignant tumors [IRR, 4.2; 95% CI, 0.9-19.2]), although this risk returned to baseline on discontinuation of IMM treatment. Patients treated with biologics (relative to biologic-naive patients) had a numerically higher risk of hematologic malignant tumors (IRR, 5.3; 95% CI, 0.7-40.5). There was no significant increase in the risk of gastrointestinal malignancies in patients with IBD compared with the general population.
CONCLUSIONS: We observed an increased risk of melanoma in IMM-treated patients with IBD, and this risk returned to baseline after discontinued use of the medications
Inflamm Bowel Dis. 2015 May 19. [Epub ahead of print]
Risk of lymphoma, colorectal and skin cancer in patients with IBD treated with immunomodulators and biologics: a Quebec claims database study.
Kopylov U, Vutcovici M, Kezouh A, et al.
BACKGROUND: Immunomodulatory medications in patients with inflammatory bowel disease (IBD) have been associated with an increased risk of developing certain malignancies. The aim of this study was to evaluate the risk of melanoma, nonmelanoma skin cancer, colorectal cancer and lymphoma associated with immunomodulators and biologics in patients with IBD.
METHODS: A nested case-control study was carried out using the provincial health insurance database of Québec, Canada (RAMQ/MedECHO).RESULTS: A total of 41,176 patients with IBD were identified of whom 19,582 patients were eligible for inclusion in the study. Treatment with thiopurine for more than 5 years was associated with a significantly increased risk of nonmelanoma skin cancer (odds ratio: 1.78; 95% confidence interval, 1.25-2.54). Immunomodulator treatment was not associated with an increased risk of non-Hodgkin's lymphoma (odds ratio: 0.87; 95% confidence interval, 0.53-1.41). Neither immunomodulators nor anti-TNF-α agents were associated with an increased risk of melanoma or colorectal cancer.
CONCLUSIONS: In a large provincial IBD cohort, treatment with immunomodulators for more than 5 years was associated with an increased risk of non-melanoma skin cancer, whereas the risk of lymphoma, melanoma, and colorectal cancer was not increased. No association was found between the risk of the evaluated malignancies and anti-TNF-α medications.
SAFETY
Bowel Dis. 2015 May 15. [Epub ahead of print]
Combined immunosuppression impairs immunogenicity to tetanus and pertussis vaccination among patients with inflammatory bowel disease.
Dezfoli S, Horton HA, Thepyasuwan N, et al.
BACKGROUND: Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known.
METHODS: We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers.
RESULTS: A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05).
CONCLUSIONS: Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.
J GastroenterolHepatol. 2015 May 13. [Epub ahead of print]
Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patient's.
Andrade P, Santos-Antunes J, Rodrigues S, et al.
BACKGROUND: Immunization against Hepatitis B virus (HBV) infection is recommended in patients with Inflammatory Bowel Disease (IBD), particularly in those under immunosuppressive therapy. Limited data are available about IBD patient's response to HBV vaccination.
AIM: We assessed the response rate to HBV vaccination in IBD patient's and evaluated the impact of different factors on the efficacy of HBV vaccination.
METHODS: Anti-HBs titers were measured in a cohort of IBD patients under treatment with infliximab and/or azathioprine. Vaccination was considered efficient when anti-HBs titers were higher than 10 UI/L.
RESULTS: We have identified 217 patients with IBD under infliximab who were vaccinated for Hepatitis B, 172 (79%) with Crohn's Disease and the remaining with Ulcerative Colitis; 114 patients (53%) were male and mean age was 33 ± 11 years. Overall, HBV vaccine was successful in 164 (76%) patients. Only 14 patients were vaccinated after infliximab was initiated and only 2 of them had antibodies levels above 10 IU/L. Among the patients that received vaccination before the beginning of infliximab, 88% of those who were vaccinated before starting azathioprine, developed antibodies, in contrast to 55% who already were under azathioprine. In multivariable analysis, treatment with infliximab [adjusted OR (95% CI): 17.642 (8.514-33.937)] and with azathioprine [adjusted OR (95% CI): 3.344 (1.653-9.145)] were the only factors associated with weaker response to HBV vaccination.
CONCLUSIONS: The response rate to the standard HBV vaccination in IBD patients is low mainly in those treated with infliximab and/or azathioprine.
