Medikamentell behandling ved IBS symptomstyrt behandling Jan G. Hatlebakk Nasjonal kompetansetjeneste for funksjonell mage-tarmsykdom Helse Bergen HF
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
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
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
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
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. 4.375 g daily Anti-diarrhoeals Dietary treatment Wilcox et al APT 2014
Antibiotica ved mistanke om bakteriell overvekst Metronidazole /Flagyl Ciprofloxacin Trimetoprim-sulfa /Bactrim Tetracycliner Rifaximin / Xifaxan
Rifaximin IBS (non-ibs-c) Pimentel et al NEJM 2011
Rifaximin IBS - retreatment Lembo et al ACG 2014
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
Antiinflammatoriske medikamenter 5-ASA eller steroider ved mistanke om mikroskopisk colitt eller lavgradig colitt Prednisolon / budesonid Mesalazin Na-chromoglykat?
Mesalazin - Satisfactory relief of the overall IBS symptoms). Giovanni Barbara et al. Gut doi:10.1136/gutjnl-2014-308188
Primary efficacy analysis (satisfactory relief of abdominal pain or discomfort). Giovanni Barbara et al. Gut doi:10.1136/gutjnl-2014-308188 Copyright BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
Behandling som er rettet mot årsak Behandling som er rettet mot patogenetiske mekanismer Gallesyreabsorsjon Antibiotica Pancreasenzymer Behandling som er egnet til å lindre symptomer
Meta-analyses effective pharmacological treatment in IBS Soluble fibre (RR=0.83; 95% CI 0.73-0.94; NNT=7) Probiotics (RR=0.79; 95% CI 0.70-0.89; NNT=7) Antispasmodics (RR=0.68; 95% CI 0.57-0.81; NNT=5) Peppermint Oil (RR=0.43; 95% CI 0.32-0.59; NNT=2.5) 5HT 3 antagonists (RR=0.78; 95% CI 0.71.0.86; NNT=7) (Cilansetron=Alosetron) Tegaserod (RR=0.85; 95% CI 0.80-0.90; NNT=10) Ford et al Am J Gastroenterol 2014 x 2 Ford Am J Gastroenterol 2009 Ford et al BMJ 2008
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
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
Edoxadoline
Probiotica Simren M Gut 2013
IBS - Probiotics McFarland et al WJG 2008
Behandling ved hard avføring Toleranse for fiber ofte lav Løselig fiber Uløselig fiber En kombinasjon av laxantia kan fungere Movicol Vi-Siblin Laxoberal
Macrogol / PEG 3350 + Electrolytes for IBS-C Chapman et al Am J Gastroenterol 2013
Linaclotide IBS-C Chey et al Am J Gastroenterol 2012
Rao et al Am J Gastroenterol 2012
Drugs in the pipeline Lubiprostone CIC-2 activator approved for IBS-C, constipation, opiate-induced constipation Avdeling / enhet
Lubiprostone - IBS-C p=0.003 p=0.003 p=0.078 4/4 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
Loperamid For lite brukt Åpne kapsler eller mikstur
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
Primary Efficacy End Point Eluxadoline IBS-D Percentage of Patients Who Met the Daily Composite Response Criteria over Time. Lembo et al NEJM 2016
Antidepressants IBS
Antidepressant receptor site effects TCA Norepinephrine Serotonin Histamine Acetylcholine Amitriptyline +++ +++ ++++ ++++ Doxepine ++ +++ ++++ ++ Desipramine +++ +++ + + Nortriptyline +++ + ++ ++ SSRI Citalopram 0 ++++ 0 0 Escitalopram 0 ++++ 0 0 Fluoxetine 0 ++++ 0 0 Paroxetine 0 ++++ 0 0 Sertraline 0 ++++ 0 0 SNRI Venlafaxine ++ ++ 0 0 Duloxetine ++++ +++ 0 0 Milnacipran ++++ ++ 0 0 TCA, Tricyclic antidepressants; SSRI, Selective serotonin reuptake inhibitors; SNRI, Serotonin-norepinephrine reuptake inhibitors; 0 ++++ = None Strong Törnblom & Drossman Neurogastroenterol Motil 2015
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
Antidepressants - IBS NNT=4 NNT=4 RR=0.66 (95% CI: 0.56-0.79) RR=0.68 (95% CI: 0.51-0.91) RR=relative risk; SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic antidepressant Ford et al Am J Gastroenterol 2014
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