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Anja St.Clair Jones Lead Pharmacist Digestive Diseases Royal Sussex County Hospital Brighton Medicines Optimisation in IBD Can we base it on evidence?

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Presentation on theme: "Anja St.Clair Jones Lead Pharmacist Digestive Diseases Royal Sussex County Hospital Brighton Medicines Optimisation in IBD Can we base it on evidence?"— Presentation transcript:

1 Anja St.Clair Jones Lead Pharmacist Digestive Diseases Royal Sussex County Hospital Brighton Medicines Optimisation in IBD Can we base it on evidence?

2 Aims and Objectives Enable medicines optimisation in IBD Understand Inflammatory Bowel Disease (IBD), Describe drugs used in treatment of IBD Develop strategies for medicines optimisation

3 Stomach Duodenum Jejunum Ileum Caecum Terminal ileum Ascending colon (Right sided/ proximal) Transverse colon Splenic flexure Descending colon (Left sided/distal) Sigmoid colon Hepatic flexure Rectum Anus

4 Epidemiology Disease of YOUNG people (peak 10-25y, 50+y) Up to 260’000 people affected in UK UC: 10/100’000 per year –prevalence 146/100’000 (NICE 2013, CG 166) –Incidence stable –Difference in ethnic groups (Ashkenazi Jews) –50% have relapse in any year –25% acute sever colitis during lifetime (NICE 2013) –90% are able to FT work 1year after diagnosis CD: 5-10/100’00 per year –prevalence 157/100’000 (NICE 2012, CG152) –Incidence increasing –75% able to work in year after diagnosis –15-20% disabled by disease within 5 years (NICE 2012) –50-80% require surgery for strictures (NICE 2012)

5 Anatomic distribution in Crohn’s

6 80% left sided only

7 Pathogenesis Theories of inflammatory bowel disease etiology -Toxic response to luminal contents -Specific microbial pathogen -Abnormal luminal constituents -Increased absorption of luminal macromolecules -Enhanced immunologic response to normal constituents -Autoimmune response -To epithelial cell or mucus glycoproteins -Molecular mimicry (cross-reactivity of intestinal microflora and epithelia) -To immune cells  Trigger – what?  Genetic involvement

8 Immune dysregulation in Crohn's disease

9 CD or UC?

10 Ulcerative colitisCrohn's disease Site of diseaseColon only Any part of gastrointestinal tract Symptoms Bleeding++++ Diarrhea+++++ Abdominal pain+++++ Growth failure++++ Tenesmus+++± Perianal disease—+ Endoscopic findings Rectal involvement++++ InflammationContinuousDiscontinuous Diffuse erythemaPatchy lesions Ulceration in inflamed mucosa Discrete ulcers in normal mucosa Complications FistulasExceedingly uncommonFrequent (? Crohn's) StricturesUncommon (? malignancy)Common Cancer risk (>10 years)Increased

11 Fistulae in IBD

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13 Diagnosis and investigations History and examination FBC, LFT, ESR or CRP Microbiological testing (C. Diff., CMV) Abdo imaging Endoscopies +/- biopsies Barium enema, small bowel studies Colonoscopy Assessment of disease extent

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15 Figure 1a and 1b: endoscopic views of Crohn’s disease showing mucosal oedema, ulceration and exudates.

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17 Crohn's Disease Activity Index CDAI = 2x1 + 5x2 + 7x3 + 20x4 + 30x5 + 10x6 + 6x7 + (weight factor)8 1. Number of liquid or very soft stools in one week 2. Sum of seven daily abdominal pain ratings: (0=none, 1=mild, 2=moderate, 3=severe) 3. Sum of seven daily ratings of general well-being: (0=well, 1=slightly below par, 2=poor, 3=very poor, 4=terrible) 4. Symptoms or findings presumed related to Crohn's disease arthritis or arthralgia iritis or uveitis erythema nodosum, pyoderma gangrenosum, apththous stomatitis anal fissure, fistula or perirectal abscess other bowel-related fistula febrile (fever) episode over 100 degrees during past week 5. Taking Lomotil or opiates for diarrhea 6. Abnormal mass 0=none; 0.4=questionable; 1=present 7. Hematocrit [ (Typical - Current) x 6 ] x [(standard weight-actual body weight) / standard weight]

18 Harvey–Bradshaw Index for Crohn's disease Number of liquid stools per day Abdominal pain, sum of seven daily ratings: (0-none, 1-mild, 2-moderate, 3-severe) Abdominal mass (0-none, 1-questionable, 2-definite, 3-definite & tender) General well being (0-very well, 1-slightly below par, 2-poor, 3-very poor, 4-terrible) Complications (score 1 point per item) Arthritis/arthalgia Skin/mouth lesions Iritis/uveitis Anal fissure, fistula/perianal abscess

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20 UC activity scores

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24 Therapeutic aim Remission Avoid surgery CRC (5x) Also: –Smoking cessation –VTE prophylaxis (always!!) –Pain control (no NSAIDs) –Osteoporosis prophylaxis –Opportunistic infections –https://www.ecco-ibd.eu/documents/ECCOconsensusOI.pdfhttps://www.ecco-ibd.eu/documents/ECCOconsensusOI.pdf

25 Treatments

26 How to optimise treatment? Correct dose Co-prescribing TDM Exit strategies Rescue strategies

27 Steroids Indication: CD and UC –Moderate to severe relapse Maximise local effect and limit systemic effect No role in maintenance –40mg OD Prednisolone reduced slowly by 5mg/week –≤ 15mg ineffective in active disease Budesonide not as effective as Pred but alternative in ileo-ascending colonic disease –Less systemic effect Osteoporosis

28 Rectal steroids Only for patient not responding to rectal mesalazine Hydrocortisone (Colifoam) 1 od-bd –High plasma levels after administration Prednisolone NaPhos (Predsol) 1 bd –Rectal mucosa only Prednisolone metosulphbenzoate (Predenema 1 od ) –Poorly absorbed –Increased spread (reached ascending colon in some patient) Prednisolone metosulphbenzoate (Predfoam 1od-bd ) –Poorly absorbed –Retained in rectum and sigmoid colon

29 Rectal steroids Rectal steroidPeak plasma nmols/LPeak tissue ng/g Prednisolone phosphate 20mg 365 (2hrs)44 Predenema Prednisolone meta- sulphbenzoate 20mg 45 (2hrs)257 Predfoam Prednisolone meta- sulphbenzoate 20mg 320 (4hrs)4874 Colifoam Hydrocortisone Acetate 125mg 510(4hrs)Not recorded

30 Optimisation Correct dose –Start at 40mg and slow reduction Correct formulation –Know where the disease is located Prevent osteoporosis Consider infection risk

31 Rectal reparations: site of action and indication FormulationSite of actionDisease extent SuppositoryRectumProctitis FoamSigmoid ColonProcto-sigmoiditis EnemaDescending colon to splenic flexure and in some cases even distal part of transverse colon. Left sided ( distal)colitis

32 5-ASA Dose: Crohn’s: –higher doses ≥ 4g no evidence (post op only) UC: –Induction of remissions ≥ 4g/day –Maintenance of remission ≥ 2g/day Rectal preparations (PINCE) –15% past splenic flexure:2g bd oral + 1g OD rectal (64% remission at week 8 vs 43% oral) Compliance at week 8 –(PODIUM: OD vs BD:71% vs 59% remission)

33 DrugFormulation Optimal drug release pH Site of drug release Mesalazine Asacol MR 400mg: Enteric coated with Eudragit S 800mg: Enteric coated with layer of Eudragit S followed by Eudragit S+L pH-dep. delayed release (>7) Terminal ileum & large bowel (colon & rectum) IpocolEnteric coated with Eudragit S>7Terminal ileum & colon Mesren MREnteric coated with Eudragit S>7Terminal ileum & colon Octasa MREnteric coated with Eudragit S>7Terminal ileum & colon Mezavant XL Film coated with methacrylate copolymers Type A, Type B Gastroresistant coating with Lipophylic and hydrophilic matrix (>7) Colon Pentasa Ethylcellulose coated microgranules to allow slow continuous release Diffusion through semi-permeable membrane (Enteral pH) Duodenum to rectum Salofalk Tablets: Enteric coated with Eudragit L Granules: Eudragit L and matrix granule structure (slow continuous release) pH-dep. delayed release (>6) and matrix Terminal ileum & colon Azo-bonded preparations Salazopyrin (Sulfasalazine) Colazide (Balsalazide) Dipentum (Olsalazide) 5-ASA +SA Prodrug Dimer Cleavage by intestinal bacteria Azoreductase (>7) Colon

34 Adherence and switching 39% adherence in maintenance Robinson; APT 2013 –61% chance of relapse vs 11% –Increased risk of CRC 31% vs 3% 75% risk reduction in adherers –Cost :14% admission = 49% of cost Kane 2006, Bassi 2004, Hawthorne 2008 Switch patients had 3.5-fold risk of relapse Endoscopic healing rate is not equivalent

35 Optimisation Top and tail in sever flares Consider switching carefully Support Adherence –Tailor formulation to patient –Reinforce message of CRC prevention –Consider switch of preparation carefully –Consider impact on endoscopic healing


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