Βιβλιογραφική ενημέρωση – Απρίλιος 2016

Βιβλιογραφική ενημέρωση - Απρίλιος 2016

Επιμέλεια: Εύη Ζαμπέλη

1. Ο δυσμενής ρόλος του καπνίσματος στην νόσο Crohn είναι γνωστός. Η παρακάτω είναι μία από τις λίγες προοπτικές μελέτες η οποία αξιολόγησε τον ρόλο του καπνίσματος στην πορεία της νόσου, σε 573 ασθενείς. Οι ασθενείς ήταν σε ύφεση κατά την ένταξη στην μελέτη. Η ομάδα των καπνιστών εκδήλωσε περισσότερες υποτροπές ενώ όσοι διέκοψαν το κάπνισμα είχαν συγκρίσιμη συχνότητα υποτροπής με τους μη καπνιστές. Η σημασία του καπνίσματος έχει επανατεθεί προσφάτως υπό την έννοια της ευρείας χρήσης ισχυρών ανοσοτροποποιητικών φαρμάκων και του κατά πόσο το κάπνισμα σε αυτό το νέο ‘περιβάλλον’ εξακολουθεί να είναι το ίδιο βλαπτικό.

Impact of Smoking Cessation on the Clinical Course of Crohn’s Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study. Am J Gastroenterol 2016; 111:411–419

Tiago Nunes MD1,11, Maria Josefina Etchevers MD1,11, Valle García-Sánchez MD2, Daniel Ginard MD3, Eva Martí MD3, Manuel Barreiro-de Acosta MD4, Fernando Gomollón MD5, Maite Arroyo MD5, Guillermo Bastida MD6, Benito Gonzalez MD7, David Monfort MD8, Esther García-Planella MD9, Carolina Figueroa MD1, Julián Panés MD1 and Miquel Sans MD, PhD1,10

Objective
Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn’s disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants.

Methods
This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years.

Results
A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10–2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20–2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use.

Conclusions
Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers.

2. Αυτή η αναδρομική μελέτη από την Ιαπωνία ανασκόπησε τις περιπτώσεις 538 ασθενών που εισήχθησαν στο νοσοκομείο λόγω οξείας αιμορραγίας κατώτερου πεπτικού. Συγκρίθηκαν η αποτελεσματικότητα και η ασφάλεια δύο ‘προσεγγίσεων’: της κολονοσκόπησης εντός (πρώιμη) και μετά το 24ωρο. Κατά την πρώιμη εξέταση υπήρχε η δυνατότητα εντοπισμού και αντιμετώπισης της εστίας της αιμορραγίας ενώ σχετίστηκε και με βραχύτερη διάρκεια νοσηλείας. Παρόλα αυτά, η διενέργεια κολονοσκόπησης εντός του 24ώρου δεν μείωσε την θνητότητα και επιπλέον, αύξησε τον κίνδυνο επαναιμορραγίας.

Safety and Effectiveness of Early Colonoscopy in Management of Acute Lower Gastrointestinal Bleeding on the Basis of Propensity Score Matching Analysis. Clin Gastroenterol Hepatol. 2016 Apr;14(4):558-64

Nagata N1, Niikura R2, Sakurai T2, Shimbo T3, Aoki T2, Moriyasu S2, Sekine K2, Okubo H2, Imbe K2, Watanabe K2, Yokoi C2, Yanase M2, Akiyama J2, Uemura N

Background & Aims
We investigated the safety and effectiveness of early colonoscopy (performed within 24 hours of hospital admission) for acute lower gastrointestinal bleeding (LGIB) vs elective colonoscopy (performed 24 hours after admission).

Methods
We conducted a retrospective study by using a database of endoscopies performed at the National Center for Global Health and Medicine in Tokyo, Japan from January 2009 through December 2014. We analyzed data from 538 patients emergently hospitalized for acute LGIB. We used propensity score matching to adjust for differences between patients who underwent early colonoscopy vs elective colonoscopy. Outcomes included rates of adverse events during bowel preparation and colonoscopy procedures, stigmata of recent hemorrhage, endoscopic therapy, blood transfusion requirement, 30-day rebleeding and mortality, and length of hospital stay.

Results
We selected 163 pairs of patients for analysis on the basis of propensity matching. We observed no significant differences between the early and elective colonoscopy groups in bowel preparation–related rates of adverse events (1.8% vs 1.2%, P = .652), colonoscopy-related rates of adverse events (none in either group), blood transfusion requirement (27.6% vs 27.6%, P = 1.000), or mortality (1.2% vs 0, P = .156). The early colonoscopy group had higher rates than the elective group for stigmata of recent hemorrhage (26.4% vs 9.2%, P < .001) and endoscopic therapy (25.8% vs 8.6%, P < .001), including clipping (17.8% vs 4.9%, P < .001), band ligation (6.1% vs 1.8%, P = .048), and rebleeding (13.5% vs 7.4%, P = .070). Patients in the early colonoscopy group stayed in the hospital for a shorter mean time (10 days) than patients in the elective colonoscopy group (13 days) (P < .001).

Conclusions
Early colonoscopy for patients with acute LGIB is safe, allows for endoscopic therapy because it identifies the bleeding source, and reduces hospital stay. However, compared with elective colonoscopy, early colonoscopy does not reduce mortality and may increase the risk for rebleeding.

3. Το ζήτημα της προληπτικής διορθικής χορήγησης ινδομεθακίνης εξετάστηκε σε αυτήν την διπλή τυφλή τυχαιοποιημένη μελέτη 449 ασθενών που υποβλήθηκαν σε ERCP, εκ των οποίων το 70% ήταν μέτριου κινδύνου για την εκδήλωση παγκρεατίτιδας. Η ινδομεθακίνη δεν φάνηκε να προστατεύει έναντι του εικονικού φαρμάκου. Σύμφωνα με τις πρόσφατες οδηγίες της ESGE συνιστάται η προφυλακτική χορήγηση της ινδομεθακίνης σε όλους τους ασθενείς που υποβάλλονται σε ERCP.

Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients.Gastroenterology. 2016 Apr;150(4):911-7

Levenick JM1, Gordon SR2, Fadden LL2, Levy LC2, Rockacy MJ2, Hyder SM2, Lacy BE2, Bensen SP2, Parr DD3, Gardner TB2

Background & Aims
Rectal indomethacin, a nonsteroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach.

Methods
We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average risk for PEP. Subjects were assigned randomly to groups given either a single 100-mg dose of rectal indomethacin (n = 223) or a placebo suppository (n = 226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a lipase level more than 3-fold the upper limit of normal, and hospitalization after ERCP for 2 consecutive nights.

Results
There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP (P = .33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped owing to futility.

Conclusions
In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604.

4. Σε αυτήν την ενδιαφέρουσα μελέτη (που συνοδεύεται και από editorial από τον Rex) οι συγγραφείς διαπίστωσαν πως το ποσοστό των επιπλοκών, 30 ημέρες μετά την κολονοσκόπηση, ήταν υψηλότερο εφόσον είχε χορηγηθεί αναισθησία με προποφόλη από αναισθησιολόγους. Αυτό αφορούσε όλα τα είδη των επιπλοκών, τόσο αυτές που σχετίζονται με την εξέταση όσο και αυτές που σχετίζονται με την αναισθησία. Ο Rex θεωρεί πως αφενός οι περιπτώσεις στις οποίες διατέθηκε αυτή η υπηρεσία πιθανώς αφορούσαν κυρίως σε θεραπευτικές εξετάσεις (με υψηλότερο κίνδυνο επιπλοκών) και αφετέρου πως η χρήση προποφόλης καθιστά αδύνατη την εκτίμηση του άλγους που μερικές φορές μπορεί να λειτουργήσει αποτρεπτικά ως προς την προώθηση του οργάνου ή και την πρόοδο της πολυποδεκτομής.

Risks Associated With Anesthesia Services During Colonoscopy. Gastroenterology. 2016 Apr;150(4):888-94

Wernli KJ1, Brenner AT2, Rutter CM3, Inadomi JM2

Background & Aims
We aimed to quantify the difference in complications from colonoscopy with vs without anesthesia services.

Methods
We conducted a prospective cohort study and analyzed administrative claims data from Truven Health Analytics MarketScan Research Databases from 2008 through 2011. We identified 3,168,228 colonoscopy procedures in men and women, aged 40–64 years old. Colonoscopy complications were measured within 30 days, including colonic (ie, perforation, hemorrhage, abdominal pain), anesthesia-associated (ie, pneumonia, infection, complications secondary to anesthesia), and cardiopulmonary outcomes (ie, hypotension, myocardial infarction, stroke), adjusted for age, sex, polypectomy status, Charlson comorbidity score, region, and calendar year.

Results
Nationwide, 34.4% of colonoscopies were conducted with anesthesia services. Rates of use varied significantly by region (53% in the Northeast vs 8% in the West; P < .0001). Use of anesthesia service was associated with a 13% increase in the risk of any complication within 30 days (95% confidence interval [CI], 1.12–1.14), and was associated specifically with an increased risk of perforation (odds ratio [OR], 1.07; 95% CI, 1.00–1.15), hemorrhage (OR, 1.28; 95% CI, 1.27–1.30), abdominal pain (OR, 1.07; 95% CI, 1.05–1.08), complications secondary to anesthesia (OR, 1.15; 95% CI, 1.05–1.28), and stroke (OR, 1.04; 95% CI, 1.00–1.08). For most outcomes, there were no differences in risk with anesthesia services by polypectomy status. However, the risk of perforation associated with anesthesia services was increased only in patients with a polypectomy (OR, 1.26; 95% CI, 1.09–1.52). In the Northeast, use of anesthesia services was associated with a 12% increase in risk of any complication; among colonoscopies performed in the West, use of anesthesia services was associated with a 60% increase in risk.

Conclusions
The overall risk of complications after colonoscopy increases when individuals receive anesthesia services. The widespread adoption of anesthesia services with colonoscopy should be considered within the context of all potential risks.

5. Η αντιμετώπιση της υψηλόβαθμης δυσπλασίας στον οισοφάγο Barrett έχει αλλάξει κατά τα τελευταία χρόνια μετά την καθιέρωση ενδοσκοπικών παρεμβάσεων όπως η βλεννογονεκτομή και οι ραδιοσυχνότητες. Η μελέτη που παρουσιάζεται εξέτασε τον ‘χειρισμό’ αυτών των ασθενών στην Αγγλία κατά την διάρκεια του έτους 2012-2013 και εντός του Εθνικού Συστήματος Υγείας. Περί το 1/3 των ασθενών δεν υποβλήθηκε σε καμία παρέμβαση. Για όσους ασθενείς ενεπλάκη και αποφάσισε ομάδα πολλών ειδικοτήτων (multidisciplinary team) η πιθανότητα ‘ενεργού’ (και ορθής) παρέμβασης ήταν σημαντικά υψηλότερη.

Management of Barrett's high-grade dysplasia: initial results from a population-based national audit. Gastrointest Endosc. 2016 Apr;83(4):736-742.e1

Chadwick G1, Groene O2, Taylor A3, Riley S4, Hardwick RH5, Crosby T6, Greenaway K7, Cromwell DA2

Background and Aims
Previous studies reported significant variation in the management of patients with Barrett’s esophagus. However, these are based on self-reported clinical practice. The aim of this study was to examine the management of high-grade dysplasia in Barrett’s esophagus in England by using patient-level data and to compare practice with guidelines.

Methods
From April 2012 to March 2013, National Health Service (NHS) trusts in England prospectively collected data on patients newly diagnosed with high-grade dysplasia (HGD) of the esophagus as part of the National Oesophago-Gastric Cancer Audit. Data were collected on patient characteristics, diagnosis and endoscopic findings, treatment planning, and therapy.

Results
Between April 2012 and March 2013, NHS trusts reported 465 cases of HGD. Diagnosis was confirmed by a second pathologist in 79.4% of cases (270/340), and 86.0% (374/465) had their treatment planned at a multidisciplinary team meeting. A total of 290 patients (62.4%) were managed endoscopically (frequently with endoscopic resection or radiofrequency ablation), whereas 26 patients (5.6%) had esophagectomy. The proportion of patients managed by surveillance varied by age (P < .001), ranging from 19.5% in patients aged <65 years to 63.8% in patients aged ≥85 years. More patients received active treatment if their cases were discussed at a multidisciplinary meeting (73.5% vs 44.3%; P < .001) or managed at higher-volume trusts (87.8% vs 55.4%; P < .001).

Conclusions
There was marked variation in the management of HGD across England, with a third of patients receiving no active treatment. Patients discussed at a specialist multidisciplinary meeting or managed in high-volume trusts were more likely to receive active treatment.

6. Ο καρκίνος του άπω στομάχου (όχι της καρδίας) αποτελεί την τρίτη συχνότερη αιτία θανάτου από καρκίνο διεθνώς. Υπάρχει μεγάλη ετερογένεια ως προς την επιδημιολογία της νόσου. Επίσης, παρότι το ελικοβακτηρίδιο του πυλωρού θεωρείται ο κύριος παθογενετικός παράγοντας, για την εκδήλωση καρκίνου χρειάζεται προφανώς η αλληλεπίδραση παραγόντων του μικροβίου με παράγοντες του ξενιστή καθώς και με άλλους περιβαλλοντικούς παράγοντες. Με δεδομένο ότι η πρόληψη πρέπει να είναι οικονομικά αποδοτική και να εξαρτάται από την κατά τόπους επίπτωση της νόσου, αναζητώνται δείκτες που θα μπορούσαν να ανιχνεύουν τον πληθυσμό ή τις μονάδες που διατρέχουν μεγαλύτερο κίνδυνο. Σε αυτήν την ενδιαφέρουσα μελέτη συγκρίθηκαν οι τρεις ακόλουθες μέθοδοι: μέτρηση πεψινογόνου, ενδοσκόπηση και αναζήτηση ελικοβακτηριδίου. Ο εργαστηριακός προσδιορισμός του πεψινογόνου σε καπνιστές (που γνωρίζουμε πως διατρέχουν περίπου Χ1.5 υψηλότερο κίνδυνο) μπορεί να είναι οικονομικά συμφέρουσα μέθοδος προκειμένου να μειωθεί η θνητότητα από εντερικό τύπου καρκίνο του στομάχου.

Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis. Gut. 2016 Apr;65(4):563-74

Yeh JM1, Hur C2, Ward Z1, Schrag D3, Goldie SJ1

Abstract Objective
To estimate the cost-effectiveness of noncardia gastric adenocarcinoma (NCGA) screening strategies based on new biomarker and endoscopic technologies.

Design
Using an intestinal-type NCGA microsimulation model, we evaluated the following one-time screening strategies for US men: (1) serum pepsinogen to detect gastric atrophy (with endoscopic follow-up of positive screen results), (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with endoscopic mucosal resection (EMR) treatment for detected lesions) and (3) Helicobacter pylori screening and treatment. Screening performance, treatment effectiveness, cancer and cost data were based on published literature and databases. Subgroups included current, former and never smokers. Outcomes included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs), expressed as cost per quality-adjusted-life-year (QALY) gained.

Results
Screening the general population at age 50 years reduced the lifetime intestinal-type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%, respectively. For all subgroups, serum pepsinogen screening was more effective and more cost-effective than all other strategies, although its ICER varied from $76 000/QALY (current smokers) to $105 400/QALY (general population). Results were sensitive to H. pylori prevalence, screen age and serum pepsinogen test sensitivity. Probabilistic sensitivity analysis found that at a $100 000/QALY willingness-to-pay threshold, the probability that serum pepsinogen screening was preferred was 0.97 for current smokers.

Conclusions
Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality.

7. Το υπερηχογράφημα χρησιμοποιείται ως μέθοδος πρόληψης του ΗΚΚ σε ασθενείς υψηλού κινδύνου. Σε αυτήν την αναδρομική μελέτη εξετάστηκε το όφελος της διενέργειας υπερηχογραφήματος ως προς την θνητότητα από ΗΚΚ. Όσο βραχύτερα ήταν τα χρονικά διαστήματα ελέγχου με υπερηχογράφημα τόσο χαμηλότερη ήταν η θνητότητα από ΗΚΚ.

Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study. Gut. 2016 Apr;65(4):693-701

Wu CY1, Hsu YC2, Ho HJ3, Chen YJ4, Lee TY3, Lin JT5

Objective
Current guidelines recommend screening for hepatocellular carcinoma (HCC) in high-risk populations. However, the effectiveness of screening in reducing mortality has been challenged. In addition, it is unclear which subgroups benefit most from HCC screening.

Design
This nationwide cohort study identified a total of 52 823 newly diagnosed HCC patients between 1 January 2002 and 31 December 2007. These HCC patients were classified into the following cohorts according to the time intervals in which they received ultrasonography screening: 0–6 months (6M), 7–12 months (12M), 13–24 months (24M), 25–36 months (36M) and not screened within 3 years (never screened). The chance to receive curative therapy and 5-year cumulative mortalities were calculated after adjusting for lead-time bias.

Results
Chances to receive curative therapy among the 6M, 12M, 24M, 36M and never screened cohorts were 24.3% (95% CI 23.7% to –24.9%), 26.9% (95% CI 25.7% to 28.2%), 22.9% (95% CI 21.8% to 24.1%), 21.3% (95% CI 19.9% to 22.8%) and 18.3% (95% CI 17.8% to 18.8%), respectively. Compared with the 6M cohort, adjusted HRs of mortality for the 12M, 24M, 36M and never screened cohorts were 1.11 (95% CI 1.07 to 1.15), 1.23 (95% CI 1.19 to 1.28), 1.31 (95% CI 1.26 to 1.37) and 1.47 (95% CI 1.43 to 1.51) (all p<0.001), respectively. On multivariable subgroup analyses, the associations between shorter screening intervals and better survival were observed in nearly all subgroups, especially in younger patients, patients without diabetes and patients with hepatitis B infection.

Conclusions
Shorter ultrasonography screening intervals are associated with reduced overall mortality in HCC patients in a dose-dependent manner.

8. Σε αυτήν την μελέτη από την Ταιβάν, συγκρίθηκαν δύο σχήματα βασισμένα στην λεβοφλοξασίνη τα οποία χορηγήθηκαν σε ασθενείς με προηγούμενη αποτυχία σε σχήμα περιέχον κλαριθρομυκίνη. Το διαδοχικό σχήμα που αφορούσε σε 5ήμερη θεραπεία με αμο/λανσο και εν συνεχεία 5ήμερη με μετρο/λεβο/λανσο, ήταν πιο αποτελεσματικό από το κλασσικό τριπλό με λεβοφλοξασίνη (αμο/λεβο/λανσο). Οι συγγραφείς παροτρύνουν την χρήση του ως δεύτερης γραμμής θεραπεία.

Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial. Am J Gastroenterol. 2016 Mar;111(3):381-7

Liou JM1, Bair MJ2,3, Chen CC1, Lee YC1, Chen MJ1, Chen CC1, Tseng CH4, Fang YJ5, Lee JY5, Yang TH5, Luo JC6, Wu JY7, Chang WH8, Chang CC9, Chen CY10, Chen PY10, Shun CT11, Hsu WF12, Hung HW13, Lin JT1,14, Chang CY3, Wu MS1

Objectives
The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment.

Methods
This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test.

Results
The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism.

Conclusions
Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori (Trial registration number: NCT01537055)

9. Στις ιδιοπαθείς φλεγμονώδεις νόσους του εντέρου δεν υπάρχουν μελέτες σύγκρισης των βιολογικών παραγόντων. Σε αυτήν την αναδρομική μελέτη έγινε σύγκριση της ινφλιξιμάμπης με την ανταλιμουμάμπη σε μία κοόρτη ασθενών με νόσο Crohn (η πλειοψηφία) και ελκώδη κολίτιδα από το 1998 μέχρι το 2010. Η πιθανότητα μη ανταπόκρισης στο 1 έτος ήταν υψηλότερη για την ανταλιμουμάμπη σε ασθενείς με νόσο Crohn. Δεν διαπιστώθηκαν διαφορές ως προς τα χειρουργεία, τις νοσηλείες και την χρήση στεροειδών. Οι συγγραφείς καταλήγουν πως οι ανωτέρω βιολογικοί παράγοντες έχουν συγκρίσιμη αποτελεσματικότητα.

Comparative Effectiveness of Infliximab and Adalimumab in Crohn's Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2016 Apr;22(4):880-5

Ananthakrishnan AN1, Cagan A, Cai T, Gainer VS, Shaw SY, Savova G, Churchill S, Karlson EW, Kohane I, Liao KP, Murphy SN

Background
The availability of monoclonal antibodies to tumor necrosis factor α has revolutionized management of Crohn's disease (CD) and ulcerative colitis. However, limited data exist regarding comparative effectiveness of these agents to inform clinical practice.

Methods
This study consisted of patients with CD or ulcerative colitis initiation either infliximab (IFX) or adalimumab (ADA) between 1998 and 2010. A validated likelihood of nonresponse classification score using frequency of narrative mentions of relevant symptoms in the electronic health record was applied to assess comparative effectiveness at 1 year. Inflammatory bowel disease–related surgery, hospitalization, and use of steroids were determined during this period.

Results
Our final cohort included 1060 new initiations of IFX (68% for CD) and 391 of ADA (79% for CD). In CD, the likelihood of nonresponse was higher in ADA than IFX (odds ratio, 1.62 and 95% CI, 1.21–2.17). Similar differences favoring efficacy of IFX were observed for the individual symptoms of diarrhea, pain, bleeding, and fatigue. However, there was no difference in inflammatory bowel disease–related surgery, hospitalizations, or prednisone use within 1 year after initiation of IFX or ADA in CD. There was no difference in narrative or codified outcomes between the 2 agents in ulcerative colitis.

Conclusions
We identified a modestly higher likelihood of symptomatic nonresponse at 1 year for ADA compared with IFX in patients with CD. However, there were no differences in inflammatory bowel disease–related surgery or hospitalizations, suggesting these treatments are broadly comparable in effectiveness in routine clinical practice

10. Η ενδιαφέρουσα όσο και παράδοξη εκδήλωση ψωρίασης σε ασθενείς με ΙΦΝΕ που λαμβάνουν αντί- TNF παράγοντες, μελετήθηκε σε αυτήν την μελέτη από την Ισπανία. Στην υπό μελέτη κοόρτη, ψωρίαση εκδηλώθηκε σε 1.7% των ασθενών. Στις γυναίκες και τους καπνιστές ήταν συχνότερη. Στα 2/3 των ασθενών το υπεύθυνο φάρμακο δεν αποσύρθηκε και η νόσος αντιμετωπίστηκε επιτυχώς με τοπικές αλοιφές. Από τους ασθενείς στους οποίους χορηγήθηκε άλλος αντί-TNF παράγοντας, ένα ποσοστό 60% εκδήλωσε πάλι ψωρίαση.

Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study. Inflamm Bowel Dis. 2016 Apr;22(4):894-901

Guerra I1, Pérez-Jeldres T, Iborra M, Algaba A, Monfort D, Calvet X, Chaparro M, Mañosa M, Hinojosa E, Minguez M, Ortiz de Zarate J, Márquez L, Prieto V, García-Sánchez V, Guardiola J, Rodriguez GE, Martín-Arranz MD, García-Tercero I, Sicilia B, Masedo Á, Lorente R, Rivero M, Fernández-Salazar L, Gutiérrez A, Van Domselaar M, López-SanRomán A, Ber Y, García-Sepulcre M, Ramos L, Bermejo F, Gisbert JP; Spanish GETECCU group (ENEIDA project)

Background
Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect.

Aim
To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients.

Methods
Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors.

Results
Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn.

Conclusions
The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.