Medikamentell behandling ved IBS symptomstyrt behandling

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1 Medikamentell behandling ved IBS symptomstyrt behandling Jan G. Hatlebakk Nasjonal kompetansetjeneste for funksjonell mage-tarmsykdom Helse Bergen HF

2 IBS Sequencing the treatments Multidisciplinary approach Patient centered Physician continuity Psychological treatment options CBT Hypnotherapy Psychotherapy Pharmacotherapy dominant symptom Constipation Diarrhea Gas/bloating Psychological - Multiple Dietary advice including probiotics Diagnosis and explanation Reassurance Precipitating factors - Life style Assessment of symptom profile and severity Törnblom & Simrén 2013

3 Behandling som er rettet mot årsak Behandling som er rettet mot patogenetiske mekanismer Gallesyreabsorsjon Antibiotica Pancreasenzymer Antiinflammatoriske medikamenter Behandling som er egnet til å lindre symptomer

4 Bile acid diarrhea IBS Effect of a bile acid binding agent Colestipol treatment (n=27) IBS Symptom Severity n=137 18% abnormal SeHCAT test Bajor et al Gut 2015

5 Bile acid diarrhea in IBS-D IBS-D Rome I, II & III IBS-D Rome III 25% 28% Slattery et al Aliment Pharmacol Ther 2015

6 Treatment Bile Acid Diarrhea Cholestyramine (Questran) 4 g daily initially, increased by 4 g at weekly intervals (in 1 4 divided doses) to max. 36 g daily. Other drugs should be taken 1 h before or 4 6 h after. Cholesevelam (WellChol) 3.75 g daily in 1 2 divided doses; max g daily Anti-diarrhoeals Dietary treatment Wilcox et al APT 2014

7 Antibiotica ved mistanke om bakteriell overvekst Metronidazole /Flagyl Ciprofloxacin Trimetoprim-sulfa /Bactrim Tetracycliner Rifaximin / Xifaxan

8 Rifaximin IBS (non-ibs-c) Pimentel et al NEJM 2011

9 Rifaximin IBS - retreatment Lembo et al ACG 2014

10 Pancreasenzymer ved mistanke om eksokrin insuffisiens Finnes hos 2-6% av pasienter diagnostisert med IBS Basert på lav f-elastase Bare 1-2% har sikker kronisk pancreatitt med rtg. / CT /EUS-funn. Talley NJ et al. J Gastroenterol Hepatol 2017

11 Antiinflammatoriske medikamenter 5-ASA eller steroider ved mistanke om mikroskopisk colitt eller lavgradig colitt Prednisolon / budesonid Mesalazin Na-chromoglykat?

12 Mesalazin - Satisfactory relief of the overall IBS symptoms). Giovanni Barbara et al. Gut doi: /gutjnl

13 Primary efficacy analysis (satisfactory relief of abdominal pain or discomfort). Giovanni Barbara et al. Gut doi: /gutjnl Copyright BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

14 Behandling som er rettet mot årsak Behandling som er rettet mot patogenetiske mekanismer Gallesyreabsorsjon Antibiotica Pancreasenzymer Behandling som er egnet til å lindre symptomer

15 Meta-analyses effective pharmacological treatment in IBS Soluble fibre (RR=0.83; 95% CI ; NNT=7) Probiotics (RR=0.79; 95% CI ; NNT=7) Antispasmodics (RR=0.68; 95% CI ; NNT=5) Peppermint Oil (RR=0.43; 95% CI ; NNT=2.5) 5HT 3 antagonists (RR=0.78; 95% CI ; NNT=7) (Cilansetron=Alosetron) Tegaserod (RR=0.85; 95% CI ; NNT=10) Ford et al Am J Gastroenterol 2014 x 2 Ford Am J Gastroenterol 2009 Ford et al BMJ 2008

16 Functional Bowel Disorders: Rome IV Type 1 Type 2 Type 3 FC Bloating C Type 4 M IBS Type 5 Type 6 FDr Distension D Type 7 Pain FC: Functional constipation FDr: Functional diarrhea IBS-C: Irritable bowel syndrome with predominant constipation IBS-D: Irritable bowel syndrome with predominant diarrhea IBS-M: Irritable bowel syndrome with mixed bowel habits (D and C) Lacy et al Gastroenterology 2016

17 Behandlingsprinsipper: Probiotica Symprove m.fl. Antibiotica rifaximin Clorid-kanal aktivatorer (CIC-2) Lubiprostone (Amitiza ) Guanylat cyclase 2c agonist Linaclotide (Constella ) Opiatagonister og antagonister Asimadoline (kappa-agonist) Eluxadoline (u-agonist, delta-antagonist) Serotonerge agonister og antagonister Prucaloprid (Resolor ) Ondansetron (Zofran ) Mastcelle stabilisatorer Na-chromoglycat Avdeling / enhet

18 Edoxadoline

19

20 Probiotica Simren M Gut 2013

21 IBS - Probiotics McFarland et al WJG 2008

22 Behandling ved hard avføring Toleranse for fiber ofte lav Løselig fiber Uløselig fiber En kombinasjon av laxantia kan fungere Movicol Vi-Siblin Laxoberal

23 Macrogol / PEG Electrolytes for IBS-C Chapman et al Am J Gastroenterol 2013

24 Linaclotide IBS-C Chey et al Am J Gastroenterol 2012

25 Rao et al Am J Gastroenterol 2012

26 Drugs in the pipeline Lubiprostone CIC-2 activator approved for IBS-C, constipation, opiate-induced constipation Avdeling / enhet

27 Lubiprostone - IBS-C p=0.003 p=0.003 p= /4 weeks with moderately relieved OR 2/4 weeks with significantly relieved Not meeting any restriction criteria Crowell Nat Rev Gastroenterol Hepatol 2009 Drossman et al Aliment Pharmacol Ther 2009

28 Loperamid For lite brukt Åpne kapsler eller mikstur

29 Ondansetron IBS-D Stool consistency FDA responder criteria Ondansetron vs. Placebo: p<0.001 n=120 IBS-D 4mg Ondansteron Dose titration allowed 5 weeks; cross-over Garsed et al Gut 2014

30 Primary Efficacy End Point Eluxadoline IBS-D Percentage of Patients Who Met the Daily Composite Response Criteria over Time. Lembo et al NEJM 2016

31 Antidepressants IBS

32 Antidepressant receptor site effects TCA Norepinephrine Serotonin Histamine Acetylcholine Amitriptyline Doxepine Desipramine Nortriptyline SSRI Citalopram Escitalopram Fluoxetine Paroxetine Sertraline SNRI Venlafaxine Duloxetine Milnacipran TCA, Tricyclic antidepressants; SSRI, Selective serotonin reuptake inhibitors; SNRI, Serotonin-norepinephrine reuptake inhibitors; = None Strong Törnblom & Drossman Neurogastroenterol Motil 2015

33 Antidepressant drug classes treatment of abdominal pain Potential benefit Side effects TCA SSRI SNRI Pain reduction Depression Sedation Constipation Hypotension Xerostoma Arrhythmias Weight gain Sexual dysfunction Depression Panic Anxiety (Pain reduction) Agitation Diarrhea Insomnia Night sweats Headache Weight loss Sexual dysfunction Pain reduction Depression Nausea Agitation Dizziness Sleep disturbance Fatigue Liver dysfunction TCA, Tricyclic antidepressants; SSRI, Selective serotonin reuptake inhibitors; SNRI, Serotonin-norepinephrine reuptake inhibitors; Törnblom & Drossman Neurogastroenterol Motil 2015

34 Antidepressants - IBS NNT=4 NNT=4 RR=0.66 (95% CI: ) RR=0.68 (95% CI: ) RR=relative risk; SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic antidepressant Ford et al Am J Gastroenterol 2014

35 Verd å ta med: Varierende effekt av eldre preparater trolig underforbruk av flere grupper inklusive TCA Effekt av nyere preparater ved IBS-C og IBS-D er lovende EMA og FDA har definert endpoints som nok underestimerer reell behandlingseffekt