Αντιμετώπιση περιεδρικής νόσου Crohn. Γ. Μιχαλόπουλος Επικουρικός Γαστρεντερολόγος Γενικό Νοσοκομείο Πειραιά «Τζάνειο»
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1 Αντιμετώπιση περιεδρικής νόσου Crohn Γ. Μιχαλόπουλος Επικουρικός Γαστρεντερολόγος Γενικό Νοσοκομείο Πειραιά «Τζάνειο»
2 ~ 25% των ασθενών με CD εκδηλώνει PCD 5% μεμονωμένη PCD PCD μπορεί να αποτελεί αρχική εκδήλωση προ της εμφάνισης της εντερικής CD (17.2% >6 μήνες προ έναρξης εντερικής νόσου) Συχνές υποτροπές (>50%) εντός διετίας Schwartz, D. A. et al. The natural history of fistulizing Crohn s disease in Olmsted County, Minnesota. Gastroenterology 122, (2002). Eglinton, T. W., Barclay, M. L., Gearry, R. B. & Frizelle, F. A. The spectrum of perianal Crohn s disease in a population-based cohort. Dis. Colon Rectum 55, (2012).
3 Ανάλογα με τη διάρκεια της νόσου αυξάνεται και το ποσοστό (12%, 15%, 21% και 26% στα 1, 5, 10 και 20 έτη νόσου) Schwartz et al. The Natural History of Fistulizing Crohn's Disease in Olrnsted County, Minnesota. GASTROENTEROLOGY 2002;122:
4 Επιπτώσεις >80% θα υποβληθούν σε κάποιου βαθμού χειρουργική θεραπεία Παραπάνω μέρες νοσηλείας(7.45 vs days, p<0.001) 20% μπορεί να χρειαστούν πρωκτεκτομή Zwintscher et al. The impact of perianal disease in young patients with inflammatory bowel disease Int J Colorectal Dis (2015) 30:
5 2/3 αναφέρουν περιορισμούς στη σεξουαλική ζωή Περιορισμούς λόγω συναισθηματικών προβλημάτων Περιορισμούς στις κοινωνικές επαφέςδραστηριότητες Επίδραση στην επαγγελματική κατάσταση (Odds Ratio 0.71; 95% CI ; P = 0.02) Vollebregt et al. Impacts of perianal disease and faecal incontinence on quality of life and employment in 1092 patients with inflammatory bowel disease. Aliment Pharmacol Ther Mar 9
6 Στο γενικό πληθυσμό τα συρίγγια προέρχονται από φλεγμαίνοντες ή διαπυημένους αδένες στις κρύπτες του πρωκτού (cryptoglandular) Το ίδιο μπορεί να συμβεί και στους ασθενείς με CD αλλά εδώ μεγάλο ρόλο παίζουν και τα διατιτραίνοντα έλκη του ορθού και του πρωκτού. Marzo World J Gastroenterol 2015
7 epithelial-to-mesenchymal transition Panés et al. Perianal fistulizing Crohn s disease: pathogenesis, diagnosis and therapy. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY 2017
8 Ενεργός ορθίτιδα Στένωση ορθού-πρωκτού 61% vs 34.3% Aγόρια 3x (παιδιατρικοί) Κορτικοστεροειδή στη διάγνωση (παιδιατρικοί) Fields S. et al. Rectal Strictures in Crohn s Disease and Coexisting Perirectal Complications. Inflamm Bowel Dis Volume 14, Number 1, January 2008 Brückner A et al. Incidence and Risk Factors for Perianal Disease in Pediatric Crohn Disease Patients Followed in CEDATA-GPGE Registry. J Pediatr Gastroenterol Nutr Jan;66(1):73-78 Hellers G. et al. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut Jun;21(6):525-7.
9 Στόχοι Κλείσιμο του στομίου? Deep tissue healing? Έλεγχος των συμπτωμάτων? Αποφυγή εκ νέου παρεμβάσεων? Ποιότητα ζωής? Απεικόνιση?
10 Patient-reported outcomes Global assessment of quality of life. Core outcome set Combined score of patient priorities. Lifestyle restriction (general) Lifestyle restriction based on toileting needs Depression Inability to attend school/work Restriction of sexual activity and avoidance of intimacy. Global assessment of incontinence. Clinician-reported outcomes A validated score to assess perianal disease activity. Development of a perianal abscess. Development of a new/recurrent fistula. Unplanned surgical reintervention. Faecal diversion or proctectomy. Imaging (optional module) Fistula response on MRI. An activity-based MRI score responsive to change. Sahnan K, et al. Gut 2018;0:1 13.
11 Αντιμετώπιση τοπικής σηπτικής επιπλοκής Tαξινόμηση (EUA- MRI/EUSενδοσκόπηση) Χειρουργικό πλάνο Φαρμακευτικό πλάνο
12 Φαρμακευτικές Θεραπείες Αντιβιοτικά Κλασσικά ανοσοκατασταλτικά (AZA, MTX) Anti-TNF Συνδυασμοί Vedolizumab Ustekinumab
13 Αντιβιοτικά Υψηλά ποσοστά υποτροπής με τη διακοπή (μέχρι 100%) Παρενέργειες λόγω μακροχρόνιας λήψης Khan et al. Antibiotic Therapy in Infl ammatory Bowel Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2011; 106: Brandt LJ et al Metronidazole therapy for perineal Crohn's disease: a follow-up study. Gastroenterology Aug;83(2):383-7.
14 Θειοπουρίνες Δεν υπάρχει RCT με θειοπουρίνες και primary end point την έκβαση της περιπρωκτικής νόσου Δεδομένα μόνο από μετα-αναλύσεις [54% (22/49) vs 21% (6/29) placebo] Pearson Ann Intern Med 1995 Dejaco et. al Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn s disease Aliment Pharmacol Ther 2003; 18:
15 Μόνο case series Μεθοτρεξάτη Mahadevan et al 9 από 16 ασθενείς ανταπόκριση (25mg IM/wk) Schroder et al. 3 εγχύσεις IFX και εν συνεχεία 20mg/wk ΜΤΧ 7 ασθενείς από 12 ανταπόκριση Ίσως σε ασθενείς με αντένδειξη για ΑΖΤ ή επί αποτυχίας άλλων μέσων. Mahadevan et al. Fistula response to methotrexate in Crohn's disease: a case series.aliment Pharmacol Ther Nov 15;18(10):
16 Anti-TNF 60 Infliximab: Complete Fistula Closure % 17/ p= % 12/32 p=0.04 placebo Infliximab 5mg/kg Infliximab 10 mg/kg % 4/31 treatment groups Present DH et al Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med May 6;340(18):
17 IFX Θεραπεία συντήρησης - ACCENT II Sands, B. E. et al. Infliximab maintenance therapy for fistulizing Crohn s disease. N. Engl. J. Med. 350,
18 Παράγοντες που σχετίζονται με ανταπόκριση σε IFX [HR] 1.88 [HR] 2.31 [HR] 1.76 [HR] 2.58 Bouguen et al. Long-term Outcome of Perianal Fistulizing Crohn s Disease Treated With Infliximab. 2013;11:
19 Trough levels??? Yarur et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn s disease. Aliment Pharmacol Ther 2017 Davidov Y et al. Association of Induction Infliximab Levels With Clinical Response in Perianal Crohn's Disease. J Crohns Colitis May 1;11(5):
20 Adalimumab-επαγωγή -CHARM Adalimumab-συντήρηση Colombel et al. Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn s Disease: The CHARM Trial. GASTROENTEROLOGY 2007;132:52 65
21 Συνδυασμοί Anti-TNF + ATBs West et. Al Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn s disease with infliximab: a double-blind placebo-controlled study Aliment Pharmacol Ther 2004; 20: Dewint et. Al Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut 2014 Feb;63(2):292-9
22 Anti-TNF + IMS SONIC Trough Jones et al. Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti- TNF Therapy for Crohn s Disease: A Metaanalysis of Placebo-controlled Trials Clinical Gastroenterology and Hepatology 2015 Bouguen et al. Long-term Outcome of Perianal Fistulizing Crohn s Disease Treated With Infliximab. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013;11:
23 Vedolizumab ENTERPRISE. ClinicalTrials.gov Identifier: NCT Sandborn et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med Aug Feagan et al. Efficacy of vedolizumab in fistulising Crohn s disease: Exploratory analyses of data from GEMINI 2. J Crohns Colitis Feb 17.
24 Ustekinumab 61% Κλινική βελτίωση (11/18) Κλινική ανταπόκριση 48.9% (22/45) Ποσοστό ύφεσης 26.7% (12/45) 6 μήνες, 33% (2/6) των ασθενών παρουσίασαν σύγκλειση όλων των συριγγίων. Sands et al. Fistula Healing in Pivotal Studies of Ustekinumab in Crohn's Disease. April 2017 Volume 152, Issue 5, Supplement 1, Page S185 Ma et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther 2017 Khorrami et al. Ustekinumab for the Treatment of Refractory Crohn s Disease: The Spanish Experience in a Large Multicentre Open-label Cohort. Inflamm Bowel Dis Volume 22, Number 7, July 2016 Battat et al. Ustekinumab for the treatment of perianal fistulas in patients with Crohn's disease. ECCO 2017
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26 Biosurgical approach ~ 50% ύφεση Kotze PG, et al. Gut 2018;0:1 14
27
Percent Cumulative. Probability. Penetrating. Inflammatory. Stricturing. Months Patients at risk N =
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