COLOSCOPY UC Early Stage Hyperemia Petechial Bleeding  Fragiability.

Presentation on theme: "COLOSCOPY UC Early Stage Hyperemia Petechial Bleeding  Fragiability."— Presentation transcript:

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4 COLOSCOPY UC Early Stage
Hyperemia Petechial Bleeding  Fragiability

5 COLOSCOPY CD Early Stage
Aphtoid Mucosal Lesions (Ulcers)

6 COLOSCOPY UC Floride (Acute) Stage
Confluating (Continious) Ulcerations Pseudopolyposis

7 COLOSCOPY CD Floride (Acute) Stage
Couble-stone relief Fissura Fistula Solitary ulcers

8 COLOSCOPY UC Late (chronic) Stage
Pseudopolyps Loss of haustra Carcinoma

9 COLOSCOPY CD Late (chronic) Stage
Stenosis Fistula Pseudopolyps Diverticula

10 Radiology / CD Couble stone Aphtoid ulcers Pseudodiverticula Fistula
Polymorph ulcers

11 Activity Index Basedon - Clinical Activity - Endoscopical Activity
- Histological Activity - Laboratory Activity

12 Activity Index /CD

13 Activity Index /UC

14 Differential Diagnosis

15 Prognosis / UC 80% chronic intermittant 15% chronic continious
10% acute fulminant The longer the chronicity The worse is the prognosis.

16 Prognosis / CD “ No absolute cure” İn 1 year 70% Remission
MILD MODERATE 30% Remission İn 1 year 70% Remission In 2 years 50% Remission 70% - Surgical Intervention POSTOP Refall 1 year 70% 2 years 50%

17 Summary -Prognosis / UC
High Rezidive – Quotient Good if isolated Procto- sigmoiditis Pancolitis  HIGH – Risk Pancolitis  often OP.

18 Summary - Prognosis / CD
High – Rezidive Quotient Complications  OP

19 Goals of Therapy for IBD
Inducing remission Maintaining remission Restoring and maintaining nutrition Maintaining patient’s quality of life Surgical intervention (selection of optimal time for surgery)

20 Pharma-Information Oral Aminosalicylates Topical Aminosalicylates
Corticosteroids Immunsuppressiva Antibiotics Biologic agents (anti TNF-alfa)

21 Oral Aminosalicylates
SULFASALACIN  COLON - Sulfapyridine – Carrier + - 5-ASA – Antiinflammatuar 5-ASA : 3-6 g/d INHIBITION - cyclooxygenase - lipooxygenase O2-Radical - neutrophil Clearance NK-ABsynthesis depression

22 Sulfasalacin Sulfapyridine - AZO-BINDING ASA Azoreductase COECUM

23 Oral Aminosalicylates
B. MESALAMIN  Ileum 5-ASA Colon 2 g/d Eudragit Capsel

24 Topical Aminosalicylates
5-ASA – FOAM SUPPOSITOIRES

25 CORTICOSTEROIDS ORAL IV use TOPICAL Prednisone 60/50/40......10 mg Or
Less side effected new forms Budesonid 9 mg/d (Endocort / Budenofalk)

26 CORTICOSTEROIDS Inhibition of : Proinflammatory Cytokines
Supportion of protective CK. (IL-4, IL 10) Inhibition of Inflammation Mediators (PAF)

27 Corticosteroids in CD: Induction of Remission
p not calculated 92%† 100 Corticosteroids 82%* Placebo 80 60%* 60 38% % Patients 40 30% 20 NCCDS ECCDS GETAID 17 weeks 18 weeks 7 weeks Clinical Remission *Randomized controlled trial †Multicenter prospective trial Malchow H et al. Gastroenterology. 1984;86:249. Modigliani R et al. Gastroenterology. 1990;98:811. Summers RW et al. Gastroenterology. 1979;77:847.

28 Remission Rates in Acute Crohn’s Studies with Budesonide CIR
Remission rates at 8 weeks (%) 70 60 50 40 30 20 10 Bud CIR Bud CIR Placebo Pentasa® Prednisolone 9 mg QD 4.5 mg BID 2 g BID 40 mg Greenberg 1994; Rutgeerts 1994; Thomsen 1998

29 Immunsuppressiva A. Azathiopyrin (AZT) 6-Mercaptopurin
- Cell replication ] B. Methotrexat (MTX) - Antimetabolite - Inhibition of Dihydrofolacid reductase + Lymphocytic Proliferation C. Cyclosporin - Immunmodulater - T-Cell depression

30 Antibiotics Metronidazol

31 Therapeutic Pyramid for Active Crohn’s Disease
Surgery Severe Immunomodulators Infliximab (Prednisone) ? Moderate Corticosteroids The therapeutic pyramid for Crohn’s disease is based upon clinical trials. Controlled release budesonide has been advocated for mild-moderate disease in countries where it is available. Infliximab has been efficacious independent of concomitant medications. (Budesonide) Mild Aminosalicylates/Antibiotics

32 Outcomes for Mild-Moderate Disease

33 Biologic agents İnfliximap adaluminap

34 Infliximab: Mechanism of Action

35 Healing of Colonic Ulceration with Infliximab
Pretreatment 4 weeks post-treatment Van Dullemen HM et al. Gastroenterology 1995;109:

36 REMICADE® (infliximab) in Patients with Fistulizing Crohn’s Disease
Present, et al. REMICADE® (infliximab) in Patients with Fistulizing Crohn’s Disease Complete Response: All Fistulas Closed P=0.04 P=0.001 * *Placebo=Conventional Therapy Present D, et al. N Engl J Med. 1999;340:

37 Incidence of Antibodies-to-Infliximab (ATI) Maintenance Studies*
Antibody-to-Infliximab (ATI) Status The most frequent AEs (by preferred term) in infliximab-treated patients in all studies were upper respiratory tract infections (27.9%), headache (25.7%), nausea (20.6%), abdominal pain (20.5%), pain (13.9%), pharyngitis (13.5%), arthralgia (13.0%), rash (12.9%), fatigue (11.9%), sinusitis (11.7%), vomiting (11.6%) fever (11.5%), diarrhea and dizziness (each 10.8%), and coughing (10.0%). % of Pts with ATI % of Patients Inconclusive† % of Pts without ATI ACCENT I CD n = 514 Week 72 ACCENT II CD n = 258 Week 54 ATTRACT RA n = 295 Week 102 ASPIRE RA n = 629 Week 54 p. 94 and 95 of ASPIRE ISS Maintenance Studies * pts with evaluable samples † pts with long-lasting serum concentrations of infliximab and never ATI (+) ASPIRE: Integrated Safety Summary, Sep. 18, 2003

38 Infliximab Infliximab indicated Exclude enteric pathogen
Exclude abscess, stricture Exclude latent/active TB (Start 6-MP/AZA or MTX) Response Observe up to 8 wks Infliximab 5 mg/kg wks 0, 2, 6 Consider steroid pre-treatment Consider acetaminophen, diphenhydramine pre-treatment Recurrent sx ≤ 4 wks Recurrent sx > 4 - < 8 wks Recurrent sx ≥ 8 wks Once a decision to treat with infliximab has been made, infectious complications need to be first guarded against by diagnosing and treating enteric pathogens, abscess, tuberculosis, or other infectious issues. Concurrent treatment with an immune modulator is desirable to minimize risk of antibodies to infliximab and subsequent loss of response. Similarly, once a course of treatment has been begun, maintenance dosing at regular intervals of 8 weeks or less should ensue, again to minimize the formation of antibodies to infliximab. Patients who do not respond to 5 mg/kg may respond to dose escalation, while patients who require treatment intervals of less than 8 weeks may be maintained at shorter intervals. Inadequate response Maintain infliximab 5 mg/kg q 4-8 wks Infliximab 10 mg/kg Inadequate response Inadequate response Surgery or investigational Rx Escalate dose or shorten interval Maintain infliximab 5 mg/kg q 8 wks Loss of response

39 Medical Management / CD
Long-term Therapy : A – IMMUNSUPPRESSIVA A2T : 25/50 MG Tbl. + - CS for Relapsing Falls B – SURGERY Remissions – maintenance - 5.ASA : 2 g/d  2 years

40 Methotrexate

41 Historical Overview 1948 – first “designer drug” specific antagonist of folic acid 1950’s – serendipitous discovery of activity in psoriasis 1960’s – widely used for psoriasis – hepatotoxic 1966 – Enderlin reported use in RA 1985 – Wienblatt defines pharmacokinetics in RA – treatment of choice for RA

42 MTX Results: Remission
50 P =0.025 % Response 25 19.1% 39.4% Placebo MTX Feagan. N Eng J Med. 1995;332(5):292-7

43 Methotrexate in IBD: Toxicity
Major Hepatic Myelosuppressive Pulmonary Fertility-related Teratogenic Enteritic/colitic Minor Gastrointestinal Alopecia-inductive Allergic Neurologic Egan LJ, Sandborn WJ. Mayo Clin Proc 1996;71:69-80

44 CD: Moderate to Severe Moderate CD Severe CD Observe Taper PO Steroids
Adequate response Adequate response Success Observe Taper PO Steroids IV Steroids Inadequate response Inadequate response Failure 6-MP/AZA Consider infliximab + 6-MP/AZA or MTX Consider surgery Adequate response Inadequate response/intolerant Maintain 6-MP/AZA or MTX Adequate response Consider change to MTX Inadequate response/intolerant Patients with more active symptoms may require a course of oral or intravenous steroids. Patients who are unable to successfully taper steroids, or who do not respond fully should be considered for 6-mercaptopurine, azathioprine, or methotrexate. Patients who do not fully respond to optimized dosing with these agents may be considered for infliximab, surgery, or investigational therapy. Maintain infliximab + 6-MP/AZA or MTX Adequate response Add infliximab Inadequate response/intolerant Surgery or investigational therapy

45 Medical Management / UC
Refractory States or Chronic active Forms Immunsuppressiva A2T : + ? Cs OP  Proctocolectomy (= Definitive Cure)

46 Ulcerative Colitis Remissions – Maintenance 5-ASA  2 gr/d

47 OP – Indications / CD Bleeding Ileus Stenosis Fistula Carcinom
Perforation Abcess

48 OP – Indications / UC Toxic Megacolon Perforation Severe Bleeding

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