Ο κίνδυνος για κακοήθεις νεοπλασίες σε ασθενείς με ιδιοπαθείς φλεγμονώδεις νόσος του εντέρου: μια μελέτη με ομάδα ελέγχου

Εισαγωγή: Υπάρχουν δεδομένα που υποστηρίζουν ότι οι ασθενείς με Ιδιοπαθείς Φλεγμονώδεις Νόσους του Εντέρου (ΙΦΝΕ) εμφανίζουν κακοήθεις νεοπλασίες (ΚΝ) έως και στο 30%. Οι ΚΝ αποτελούν την 2η αιτία θανάτου στις ΙΦΝΕ, μετά τα καρδιαγγειακά, όπως στον γενικό πληθυσμό. Σκοπός και Μέθοδος: Η καταγραφή των ΚΝ σε ασθενείς με ΙΦΝΕ από 06/2012- 06/2022 της βάσης δεδομένων και η αντιστοίχιση αυτών με ασθενείς με ΙΦΝΕ χωρίς ΚΝ [1:3 ως προς την διάγνωση (νόσο Crohn ΝC και ελκώδη κολίτιδα ΕΚ), την ηλικία (+-5χρόνια) και το φύλο] ώστε να αναδειχτούν πιθανοί παράγοντες κινδύνου ανάπτυξης ΚΝ. Αποτελέσματα: Από τους 2.382 ΙΦΝΕ ασθενείς της βάσης δεδομένων του Πανεπιστημιακού Γενικού Νοσοκομείου Ηρακλείου και του Βενιζελείου Γενικού Νοσοκομείου Ηρακλείου 107 (4.5 %) διαγνώστηκαν ΚΝ κατά την παρακολούθηση της ΙΦΝΕ ενώ 22 (0.92 %) είχαν ΚΝ πριν τη διάγνωση ΙΦΝΕ. Στον Πίνακα 1 περιλαμβάνονται τα βασικά δημογραφικά και κλινικά χαρακτηριστικά, και δεδομένα θεραπείας, των ασθενών με και χωρίς ΚΝ και ΙΦΝΕ (107 με ΚΝ και 321 χωρίς). Από αυτούς με ΚΝ οι 49 (45.8%) ήταν γυναίκες, 54 (50.5%) είχαν ΝC, η διάμεση ηλικία διάγνωσης της ΚΝ ήταν τα 61 έτη (51.3-69.8) και η διάμεση διάρκεια ΙΦΝΕ ήταν 10 έτη (0-40). Τριάντα τρείς ασθενείς (30.8%) με ΚΝ-ΙΦΝΕ είχαν γνωστό οικογενειακό ιστορικό ΚΝ και 28 (26.1 %) ήταν ενεργοί καπνιστές ενώ 46 (42.9 %) πρώην καπνιστές. Αποκλειστικά μη ανοσοκατασταλτική αγωγή είχαν λάμβαναν οι 61 (57%), οι 38 (35.5%) είχαν εκτεθεί σε ανοσοκατασταλτικά κάποια στιγμή, οι 32 (29.9%) σε anti-TNFs, οι 20 (18.7%) σε άλλους βιολογικούς παράγοντες και τέλος μόνο 8 (7.5%) είχαν λάβει συνδυαστική θεραπεία. Η πλειοψηφία των ασθενών με ΚΝ ήταν εξω-εντερικές, μόνο 12 (10.9 %) είχαν καρκίνο παχέος εντέρου και 11 (10.3 %) είχαν υποτροπή της ΚΝ ενώ 19 (17.8 %) απεβίωσαν εξαιτίας της. Στην μονοπαραγοντική ανάλυση η διάμεση διάρκεια ΙΦΝΕ (OR 0.96, CI 95%0.94- 0.99), ο φλεγμονώδης φαινότυπος στην NC (OR 0.46, CI 95% 0.23-0.93) και η θεραπεία με άλλους βιολογικούς παράγοντες (μη anti-TNFs) (OR 0.50, CI 95%0.29- 0.86) ήταν προστατευτικοί παράγοντες, ενώ η εντόπιση της NC στο παχύ έντερο (OR 3.24, CI 95% 1,49-7,04) βρέθηκε να είναι παράγοντας κινδύνου για ανάπτυξη ΚΝ (Πίνακας 1). Δεν βρέθηκε συσχέτιση με τα χαρακτηριστικά της ΙΦΝΕ, το κάπνισμα, το οικογενειακό ιστορικό ΚΝ και τις εξωεντερικές εκδηλώσεις. Στην πολυπαραγοντική ανάλυση μόνο ο φλεγμονώδης φαινότυπος της NC (OR 0.28, CI 95%0.09-0.58) ήταν προστατευτικός παράγοντας ενώ η εντόπιση στο παχύ έντερο παρέμεινε παράγοντας κινδύνου για ΚΝ (OR 4.8, CI 95% 1.81-12.79) (Πίνακας 2). Συμπεράσματα: Τα κλινικά και δημογραφικά χαρακτηριστικά των ασθενών καθώς και η χρήση ανοσοκατασταλτικής αγωγής δεν φάνηκε να σχετίζεται με την ανάπτυξη ΚΝ σε ασθενείς με ΙΦΝΕ. Μόνο ο φαινότυπος και η εντόπιση της NC ίσως παίζει ρόλο.Backgroung: There is evidence that about 30% of the patients with inflammatory bowel disease (IBD) develop malignancies which constitute the second cause of death, after cardiovascular diseases, such as in general population. Methods: The aim of this study was to investigate possible risk factors for development of malignancies in IBD patients followed in two tertiary centres. It was a retrospective analysis of prospectively recorded data in an established IBD registry for seven years (06/2012 to 12/2022). IBD patients with malignancies were compared with controls-IBD patients without malignancies [matching 1:3 according to sex, IBD diagnosis (Ulcerative Colitis; UC, Crohn’s Disease; CD) and age (±5 years)] so as to elucidate possible risk factors for cancer (CA) development in these individuals. Results: From a total of 2.382 IBD patients of the IBD registry in University Hospital and Benizelion General Hospital of Heraklion in Crete, 107 (4.5 %) were diagnosed with CAs during their follow-up whereas 22 (0.92 %) had a history of CA before IBD diagnosis. Demographic, clinical and therapeutic data for the total of 428 patients (107 with CA and 321 without CA) are presented in Table 1. Among patients with CA, 49 (45.8%) were females, 54 (50.5%) had CD, the median age of CA diagnosis was 61 years (51.3-69.8) and the median IBD duration was 10 years (0-40). Thirty-three (30.8 %) of the CA-IBD patients had known familial history of CA and 28 (26.1%) were active smokers whereas 46 (42.9 %) were ex-smokers. Thirty-eight patients (35.5%) were exposed to immunomodulators, 32 (29.9%) to anti-TNFs, 20 (18.7%) to other biologics and 8 (7.5%) to combination treatment. The majority of CA cases were extra-intestinal, only 12 (10.9%) had colorectal cancer (CRC) and 11 (10.3%) had a CA recurrence whereas 19 (17.8%) died from the CA. In the univariate analysis the median IBD duration (OR 0.96, CI 95% 0.94- 0.99), inflammatory phenotype in CD (OR 0.46, CI 95% 0.23-0.93) and treatment with other biologics (other than ant-TNFs) (OR 0.50, CI 95%0.29- 0.86) were protective factors, whereas colonic location in CD (OR 3.24, CI 95% 1,49-7,04) found to be a risk factor for CA development (Table 1). No association with disease characteristics, smoking habits, family history of CA and extra intestinal manifestations was found. In the multivariate analysis only CD inflammatory phenotype (OR 0.28, CI 95%0.09-0.58) was a protective factor whereas colonic location (OR 4.8, CI 95% 1.81-12.79) remained a risk factor for malignancies (Table 2). Conclusions: The majority of the examined demographic and clinical characteristics including use of advanced medications are not associated with the development of malignancies in patients with IBD. Only CD phenotype and location maybe plays a role

Effectiveness of third-class biologic treatment in Crohn's disease : a multi-center retrospective cohort study

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Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn’s disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach

Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease

Purpose The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. Methods Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. Results One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. Conclusions In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies

Mucocutaneous manifestations in patients with inflammatory bowel disease: a decade study from a Greek cohort

Background We sought to investigate the prevalence of mucocutaneous manifestations (MCM) and potential associations with clinical characteristics in Greek patients with IBD. Methods This was a retrospective observational single-center study. Patients with IBD diagnosis attending a tertiary referral hospital in Heraklion, Crete, from January 2010 to January 2020 were included. Data were extracted with relevant medical information from the IBD registry. Standard statistical tests, descriptive statistics tests, chi-square, Pearson correlation and multivariate analysis tests were performed, using IBM SPSS Statistics 25. Results A total of 806 IBD patients were included in the study: 463 (57.4%) males, 441 (54.7%) Crohn’s Disease, 352 (43.7%) ulcerative colitis and 13 (1.6%) IBD unclassified (IBD-U). Mean age was 50.67 +/- 17.67 years, mean age of IBD diagnosis 36.67 +/- 16.53 years and mean disease duration 13.65 +/- 9.89 years. The prevalence of MCM was 171/806 (21.2%), 9.65% in ulcerative colitis and 30.84% in CD. The presence of MCM was significantly correlated with younger age of IBD diagnosis, longer IBD duration, CD diagnosis, inflammatory behavior and ileal or ileocolonic location of CD, extensive colitis in ulcerative colitis, intestinal manifestations (EIMs) and treatment with immunosuppressant or anti-TNFa. The development of MCM was independently associated with the presence of other EIMs odds ratio (OR), 4.03 [95% confidence interval (CI), 2.60-6.24; P < 0.001] and treatment with immunosuppressant (OR, 1.87; 95% CI, 01.14-3.07; P = 0.013) or anti-TNFa (OR = 2.47; 95% CI, 1.59-3.84; P < 0.01). Conclusions In our study, about one-fifth of IBD patients developed MCM that was more frequently present in CD than in ulcerative colitis

Analysis of Clinical Trial Screen Failures in IBD: Real World Results from the IOIBD

peer reviewedBackground: Recruitment rates for phase 2b/3 randomized controlled trials (RCTs) in IBD have substantially dropped over time. Several steps are required prior to successful patient randomization. Initially the physician must propose a trial to a potentially eligible patient during a pre-screening process (step 1). This is followed by patient’s acceptance or refusal (step 2). Finally, after informed consent the patient undergoes trial screening to ensure they meet all eligibility criteria (step 3). Evaluating each step separately, this study aims to assess reasons why IBD patients are not included in RCT and patients’ outcome after screen failure (SF). Methods: All IOIBD member physicians (n=58) were invited to participate. To assess steps 1 and 2, consecutive IBD patients in relapse for whom a treatment change was required were prospectively included over a 4-week period. Reasons that prevented the IBD physician offering a sponsored multicenter phase 2b/3 RCT (step 1) and reasons why the patient accepted or refused to participate (step 2) were assessed through a physician and a patient survey, respectively. Reasons for SF (step 3) from the last 6 months, including the 4 weeks of steps 1-2, were collected retrospectively. Results: A total of 104 (59 male, 62 CD, mean age of 37.2 years) and 102 patients (58 male, 63 CD, mean age of 40.6 years) from 12 centers were included in steps 1-2 and 3, respectively (Tables 1). Among 104 patients in relapse for whom a treatment change was required, 41 (39.4%) were offered a RCT. Of the 28 who consented to RCT, 5 failed their screening (SF rate of 17.9%) and 23 were included. Main reason that prevent IBD physicians from offering an RCT (step 1) were comorbidities (n=15), reluctance to accept risk of assignment to placebo (n=12) and physicians’ preference for an alternate treatment option (n=12). After receiving information about RCT, major reasons why patients accepted or refused to participate included the trust they had in their IBD specialist and the risk of being assigned to a placebo, respectively (step 2). Regarding 102 patients included in step 3, main reasons of SF were insufficient disease activity (n=37), concurrent infection (n=15) and dropout (n=12) (Figure 1). Half of SFs could have been avoided by thorough prescreening. After SF, 51 patients were treated with commercially available therapy, 14 were rescreened for the same RCT (after resolution of the issue leading to SF), no treatment was required for 14, 10 were referred to surgery and 6 were screened for another RCT (the outcome was unknown for 7). Conclusion: This first multicentric study reported a SF rate of 17.9%. Insufficient disease activity and the risk of assigning the patient to a placebo seem to be barriers to inclusion. Half of SFs could have been avoided by better pre-screening