1 / 67

REZULTATI PRIMJENE BIOLO KE TERAPIJE U IBD doc. dr. sc. M. Bevanda SKB MOSTAR

gervaise
Download Presentation

REZULTATI PRIMJENE BIOLO KE TERAPIJE U IBD doc. dr. sc. M. Bevanda SKB MOSTAR

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


    1. REZULTATI PRIMJENE BIOLOKE TERAPIJE U IBD doc. dr. sc. M. Bevanda SKB MOSTAR

    4. Klinicke znacajke

    5. Crohnova bolest - Crohnova bolest je kronicnog tijeka - Nepoznate etiologije - Imunoloki cimbenici su ukljuceni u patogenezu bolesti - Genetska pozadina u nastajanju bolesti je za sada djelomicno istraena - Lokalizacija bolesti moe biti du cijelog GI trakta - Nakon kirurkog zahvata bolest moe recidivirati - Najcece lokalizacije upale * terminalni ileum, * debelo crijevo * ostali dijelovi tankog crijeva.

    7. KLINICKA SLIKA

    8. Zglobovi - artritis Koa eritema nodosum, pioderma gangrenosum Oci - iridociklitis Jetra primarni sklerozirajuci kolangitis Ekstraintestinalni simptomi

    9. KOMPLIKACIJE Obzirom na stupanj promjena na sluznici bolest moe imati inflamatorni stenozirajuci i penetrantni karakter (Cosnes, 2002) U pocetku dominiraju inflamatorni oblici, a s trajanjem se povecava ucestalost stenozirajuceg i penetrirajuceg oblika bolesti

    10. KOMPLIKACIJE

    11. AKTIVNOST BOLESTI Za procjenu aktivnosti bolesti koriste se: SE, Hct, Hb, fibrinogen CRP proizvode ga hepatociti, stimulirani od strane IL-1b, IL-6, TNF-a Poviene vrijednosti CRP dobro pozitivno koreliraju sa stupnjem teine bolesti (Vermeire i sar., 2005) CRP dobro pozitivno korelira i sa CDAI i CDEIS skorom, kao i sa IL-6 i amiloidom (Vermeire i sar., 2004; Soler, 2005)

    12. SKOROVI AKTIVNOSTI Klinicki skorovi CDAI (Crohns Disease Activity Index) score Cape Town score Fukoka score Harwey Bradshow score Endoskopski skorovi CDEIS (Crohn Disease Endoscopic Index of Severity) score Rutgeerts score Simple Endoscopic Score for Crohns Disease (SES-CD)

    13. RUTGEERTS SCOR

    14. Ciljevi lijecenja: Brzo uvodenje bolesnika u remisiju Postizanje poeljnog intenziteta lijecenja: Prihvatljiv odnos koristi i rizika lijecenja Prihvatljivi trokovi lijecenja za drutvo Mijenjanje prirodnog tijeka bolesti?

    15. Ciljevi lijecenja: Postizanje poeljnog intenziteta lijecenja: odravanje remisije bez uporabe steroida boljitak kvalitete ivota bolesnika cijeljenje sluznice crijeva smanjenje potrebe za hospitalizacijom i kirurkim zahvatima djelotvorno lijecenje fistula djelotvorno lijecenja ekstraintestinalnih manifestacija bolesti

    16. Put razvoja optimalnog lijecenja

    17. Steroidi u lijecenju Crohnove bolesti: koristi za bolesnika

    18. Steroidi izazivaju teke nuspojave Osteoporoza/osteonekroza Povecanje rizika infekcija Edem/Cushingov sindrom Katarakta/glaukom Usporenje rasta Promjene ponaanja Strije Diabetes Kardiovaskularne komplikacije

    19. Azatioprin moe odravati klinicku remisiju u dijela, ali ne i u svih bolesnika

    20. Ranije uvodenje imunosupresiva ne smanjuje potrebu za kirurkim zahvatima

    21. TNF a Early on, the great interest in TNF was based on the hope in its potential as an anti-cancer drug. Clinical observations in cancer patients, as well as data from experiments with animal tumor models, gave the molecule the name Tumour Necrosis Factor, due to its biological activity. However, it soon became evident that TNF does not act solely by inducing necrosis of tumor tissue, but also has a systemic endotoxic activity leading to fever, hypotension, and shock. Further studies revealed that TNF is one of the most prominent inflammatory mediators and absolutely central in starting off the inflammatory reactions of the innate immune system, including induction of cytokine production, activation or expression of adhession molecules, and growth stimulation. Potent biological activity of TNF also explains the danger of tissue damage when TNF action is not carefully controlled. Early on, the great interest in TNF was based on the hope in its potential as an anti-cancer drug. Clinical observations in cancer patients, as well as data from experiments with animal tumor models, gave the molecule the name Tumour Necrosis Factor, due to its biological activity. However, it soon became evident that TNF does not act solely by inducing necrosis of tumor tissue, but also has a systemic endotoxic activity leading to fever, hypotension, and shock. Further studies revealed that TNF is one of the most prominent inflammatory mediators and absolutely central in starting off the inflammatory reactions of the innate immune system, including induction of cytokine production, activation or expression of adhession molecules, and growth stimulation. Potent biological activity of TNF also explains the danger of tissue damage when TNF action is not carefully controlled.

    23. Uloga proinflamatornih citokina u Chronovoj bolesti Slide 15 Crohns disease is a serious, debilitating, chronic disorder that profoundly disrupts the physical, social and emotional well-being of affected patients. Although the precise cause of Crohns disease remains unknown, evidence suggests that dysregulation of cytokines that coordinate the host immune system may play a significant role in the perpetuation of chronic inflammation. Tumour necrosis factor-alpha (TNF?) is a known, highly pro-inflammatory cytokine. Increased concentrations of TNF? seen in people with inflammatory diseases suggest that TNF? plays an early, central role in the cytokine cascade of the inflammatory process. Released by activated T cells and macrophages, TNF? stimulates the production of the potent pro-inflammatory interleukins (IL), IL-1, IL-6, IL-8, and granulocyte- macrophage colony-stimulating factor (GM-CSF). Together, these cytokines provoke a humoral immune response and activate other cellular inflammatory pathways, including those mediated by leukotrienes, superoxides, nitric oxide and prostaglandins. In patients with Crohns disease, TNF? also recruits circulating inflammatory cells to the local tissue site of inflammation, induces oedema, prompts coagulation activation and plays a pivotal role in granuloma formation. Overactivity of these pathways in patients with Crohns disease, stimulated by upregulation of TNF?, ultimately results in inflammation of, and damage to, intestinal submucosa. Slide 15 Crohns disease is a serious, debilitating, chronic disorder that profoundly disrupts the physical, social and emotional well-being of affected patients. Although the precise cause of Crohns disease remains unknown, evidence suggests that dysregulation of cytokines that coordinate the host immune system may play a significant role in the perpetuation of chronic inflammation. Tumour necrosis factor-alpha (TNF?) is a known, highly pro-inflammatory cytokine. Increased concentrations of TNF? seen in people with inflammatory diseases suggest that TNF? plays an early, central role in the cytokine cascade of the inflammatory process. Released by activated T cells and macrophages, TNF? stimulates the production of the potent pro-inflammatory interleukins (IL), IL-1, IL-6, IL-8, and granulocyte- macrophage colony-stimulating factor (GM-CSF). Together, these cytokines provoke a humoral immune response and activate other cellular inflammatory pathways, including those mediated by leukotrienes, superoxides, nitric oxide and prostaglandins. In patients with Crohns disease, TNF? also recruits circulating inflammatory cells to the local tissue site of inflammation, induces oedema, prompts coagulation activation and plays a pivotal role in granuloma formation. Overactivity of these pathways in patients with Crohns disease, stimulated by upregulation of TNF?, ultimately results in inflammation of, and damage to, intestinal submucosa.

    24. Uloga TNFa u upalnim bolestima crijeva The central abnormality in CD is an imbalance of proinflammatory and anti0inflammatory mediators in the gastric mucosa. There is an enhanced T helper cell response (Th1) with cytokine involvement of IFNgamma and TNFalpha. In the mucosa of many patients with active CD, the cytokines critical for generation of a Th1 response (IFNgamma, TNFalpha, Il-18, and Il-12) are increased. TNFalpha is a molecule produced by macrophages and T cells. The importance of TNFalpha in inflammation has been directly demonstrated in the TNFalpha knock in model. The model, which is engineered to produce high and persistent levels of TNFalpha, reproduces a transmural infalmmatory ileal disease similar to CD. In the majority of mouse models, antibodies to TNFalpha either prevent or attenuate inflammation. This response is paralleled by downmodulation of Th1 cytokine production. The central abnormality in CD is an imbalance of proinflammatory and anti0inflammatory mediators in the gastric mucosa. There is an enhanced T helper cell response (Th1) with cytokine involvement of IFNgamma and TNFalpha. In the mucosa of many patients with active CD, the cytokines critical for generation of a Th1 response (IFNgamma, TNFalpha, Il-18, and Il-12) are increased. TNFalpha is a molecule produced by macrophages and T cells. The importance of TNFalpha in inflammation has been directly demonstrated in the TNFalpha knock in model. The model, which is engineered to produce high and persistent levels of TNFalpha, reproduces a transmural infalmmatory ileal disease similar to CD. In the majority of mouse models, antibodies to TNFalpha either prevent or attenuate inflammation. This response is paralleled by downmodulation of Th1 cytokine production.

    25. Neravnotea citokina u CD

    26. Dva oblika TNFa TNF itself stays membrane bound as a pre-protein and is cleaved off byu metalloproteinases to be released from the producer cells as mature soluble TNF. All TNF molecules form trimers in order to bind to the receptor. TNF molecules have to trimerize to be able to activate TNF receptors. Homotrimer of three 17kDa TNF molecules. TNF itself stays membrane bound as a pre-protein and is cleaved off byu metalloproteinases to be released from the producer cells as mature soluble TNF. All TNF molecules form trimers in order to bind to the receptor. TNF molecules have to trimerize to be able to activate TNF receptors. Homotrimer of three 17kDa TNF molecules.

    27. Dva TNFa receptora The two TNFRs share structural similarities in their extracellular domains, but differ in their intracellular domains, their signal transduction pathways, and consequently, their function. Both receptors are transmembrane glycoproteins with myltiple cysteine-rich repeats in the extracellular N-terminal domains. The two TNFRs share structural similarities in their extracellular domains, but differ in their intracellular domains, their signal transduction pathways, and consequently, their function. Both receptors are transmembrane glycoproteins with myltiple cysteine-rich repeats in the extracellular N-terminal domains.

    28. TNFR2 The second membrane-bound TNFreceptor is the 75-80kDa TNFR2. While it shares some structural homology with TNFR1, there is no death domain within the intracellular part of the receptor and thus, this receptor cannot signal for apoptosis. the prominent interaction upon activation of the TNFR2 by TNFalpha is the recruitment of TRAF2 and the activation of the NFkB pathway. This results not only in the production of cytokines The second membrane-bound TNFreceptor is the 75-80kDa TNFR2. While it shares some structural homology with TNFR1, there is no death domain within the intracellular part of the receptor and thus, this receptor cannot signal for apoptosis. the prominent interaction upon activation of the TNFR2 by TNFalpha is the recruitment of TRAF2 and the activation of the NFkB pathway. This results not only in the production of cytokines

    29. Infliximab: mehanizam djelovanja promotes the healing of fistulae in Crohns Diseasae for which few therapeutic options are available. As multiple mechanisms are involved in producing the inflammation in Crohns Disease, new targeted biological therapies are being tried. The first of these to gain widespread use in Infliximab. A single infusion can induce remission in about two-thirds of patients with active Crohns disease. Three infusions over six weeks can also lead to closure of fistulae in 50% of patients. Repeated infusions at eight-weekly intervals will maintain remisison in over 60% of patients who respond initially promotes the healing of fistulae in Crohns Diseasae for which few therapeutic options are available. As multiple mechanisms are involved in producing the inflammation in Crohns Disease, new targeted biological therapies are being tried. The first of these to gain widespread use in Infliximab. A single infusion can induce remission in about two-thirds of patients with active Crohns disease. Three infusions over six weeks can also lead to closure of fistulae in 50% of patients. Repeated infusions at eight-weekly intervals will maintain remisison in over 60% of patients who respond initially

    30. Doziranje:

    31. Ucinak Infliximaba 2) An article in the New England Journal of Medicine reports of a clinical trial concluding that Infliximab is an efficacious treatment for fistulas in patients with Crohns disease. 3) Repeated infusions at eight =-weekly intervals will maintain remission in over 60% of patients who respond initially. 2) An article in the New England Journal of Medicine reports of a clinical trial concluding that Infliximab is an efficacious treatment for fistulas in patients with Crohns disease. 3) Repeated infusions at eight =-weekly intervals will maintain remission in over 60% of patients who respond initially.

    32. Sigurnost i nus ucinak Infliximaba: The potential for development of adverse reactions with anti-TNF agents is an unfortunate limitation to this therapy. Because its molecular structure is only 25% murine, your body reacts to this non-self protein as an Antigen, and can potentially launch an immune response against it. Infusion reactions are common, such as pruritis, flushing and nausea. May prevent further use. TNFalpha is a critical mediator of inflammation and may play a role in other aspects of immune pathology. Thus, inhibitioin of this molecule is associated with a higher risk of serious infection due to immunosuppression. TB is the most commonly reported infection associated with infliximab therapy in the USA, where it results from the reactivation of latent infection in the non-immunised population. Immunosuppressive agents can also increase the risk of non-Hodgkins lymphoma Risk/benefit assessment is recommended before prescribing these drugs to patients. Of the new biological agents, those with appreciable non-human content are most likely to be immunogenic. Antibody production can be reduced by concurrent use of corticosteroids. The potential for development of adverse reactions with anti-TNF agents is an unfortunate limitation to this therapy. Because its molecular structure is only 25% murine, your body reacts to this non-self protein as an Antigen, and can potentially launch an immune response against it. Infusion reactions are common, such as pruritis, flushing and nausea. May prevent further use. TNFalpha is a critical mediator of inflammation and may play a role in other aspects of immune pathology. Thus, inhibitioin of this molecule is associated with a higher risk of serious infection due to immunosuppression. TB is the most commonly reported infection associated with infliximab therapy in the USA, where it results from the reactivation of latent infection in the non-immunised population. Immunosuppressive agents can also increase the risk of non-Hodgkins lymphoma Risk/benefit assessment is recommended before prescribing these drugs to patients. Of the new biological agents, those with appreciable non-human content are most likely to be immunogenic. Antibody production can be reduced by concurrent use of corticosteroids.

    33. Immunogenost Infliximaba

    34. Koji bolesnici mogu imati koristi od primjene infliximaba? Do 58% bolesnika postaje rezistentno na steroide/imunosupresive

    35. Koji su bolesnici nepotpuno kontrolirani kombinacijom steroida/AZA? Do 58% bolesnika postaje rezistentno na steroide/AZA

    36.

    37.

    38. Prednosti redovite primjene infliksimaba

    39. Ekstraintestinalne manifestacije, komorbidnosti i komplikacije Crohnove bolesti

    40. Odravanje remisije: usporedba epizodne nasuprot redovitoj primjeni lijeka Epizodno Na pocetku lijecenja ili u slucaju pogoranja bolesti Redovita Infuzije u 8-tjednim razmacima

    41. Redovito lijecenje infliksimabom sigurno je kao i epizodno

    42. Optimalna uporaba infliksimaba u Crohnovoj bolesti: zakljucci temeljeni na dosadanjim iskustvima U bolesnika s umjerenim ili tekim oblikom Crohnove bolesti, infliksimab: Inducira i odrava klinicku remisiju Smanjuje potrebu za steroidima Omogucuje cijeljenje sluznice crijeva Smanjuje ucestalost hospitalizacija i kirurkih zahvata

    43. Ulcerozni kolitis - Kronicna bolest s brojnim remisijama i egzacerbacijama - Posljedica poremecenog imunosnog odgovora geneticki susceptibilnih osoba - Pocinje u rektumu i iri se proksimalno - Zahvaca sluznicu, u manjoj mjeri submukozu - Puenje zatitni cimbenik bolesti - pouchitis-posljedica kirurkog lijecenja UK

    44. Prezentacija i distribucija bolesti Slide 5 In a study conducted between 1960 and 1983 of 1,116 Cleveland Clinic Foundation patients with a confirmed UC diagnosis for whom follow-up was at least 5 years, the characteristics of the disease were reported as follows: Disease location could be defined in one of three categories: Proctosigmoiditis (46.2%) Pancolitis (36.7%) Left-sided colitis (17%) The mean age at diagnosis was 32 years. Early complications (within two years of diagnosis) included: colonic hemorrhage (16.7%) and toxic colitis (12.7%). Complications were highest among patients with pancolitis. Surgery was required for 37.6% of the patients. Disease extended in 53.8% of cases. References Farmer RG, Easley KA, Rankin GB. Clinical patterns, natural history, and progression of ulcerative colitis. Dig Dis Sci 1993;38(6):1137-1146.Slide 5 In a study conducted between 1960 and 1983 of 1,116 Cleveland Clinic Foundation patients with a confirmed UC diagnosis for whom follow-up was at least 5 years, the characteristics of the disease were reported as follows: Disease location could be defined in one of three categories: Proctosigmoiditis (46.2%) Pancolitis (36.7%) Left-sided colitis (17%) The mean age at diagnosis was 32 years. Early complications (within two years of diagnosis) included: colonic hemorrhage (16.7%) and toxic colitis (12.7%). Complications were highest among patients with pancolitis. Surgery was required for 37.6% of the patients. Disease extended in 53.8% of cases. References Farmer RG, Easley KA, Rankin GB. Clinical patterns, natural history, and progression of ulcerative colitis. Dig Dis Sci 1993;38(6):1137-1146.

    45. Ulcerozni kolitis: Slide 6 The prognosis of UC including survival, colectomy rate, activity of disease, and working capacity was estimated from a follow-up study of 783 patients with UC comprising all patients from the county of Copenhagen. The period of observation ranged from 1 to 18 years with a mean of 6.7 years. The following observations were made: The survival rate of woman did not differ from that of the general population. At diagnosis, men over age 40 had a slight excess mortality rate in the first 2 years after diagnosis. Colon cancer was seen in only 7 of 783 patients. Annual risk was 0.07%. The colectomy rate was 9.6% in first year of diagnosis. After 10 years, the colectomy rate was 23%. After 18 years, the colectomy rate was 31%. At 3 years after diagnosis, the capacity to work including those with colectomy was not different from that of the general population. The study also indicated that, at any given time, 50% of those with UC were without symptoms, 30% had low disease activity, and 20% had moderate to high disease activity. Within 10 years of diagnosis, 97% of patients experienced at least one relapse. References Hendriksen C, Kreiner S, Binder V. Long term prognosis in ulcerative colitis based on results from a regional patient group from the county of Copenhagen. Gut 1985; 26:158-163.Slide 6 The prognosis of UC including survival, colectomy rate, activity of disease, and working capacity was estimated from a follow-up study of 783 patients with UC comprising all patients from the county of Copenhagen. The period of observation ranged from 1 to 18 years with a mean of 6.7 years. The following observations were made: The survival rate of woman did not differ from that of the general population. At diagnosis, men over age 40 had a slight excess mortality rate in the first 2 years after diagnosis. Colon cancer was seen in only 7 of 783 patients. Annual risk was 0.07%. The colectomy rate was 9.6% in first year of diagnosis. After 10 years, the colectomy rate was 23%. After 18 years, the colectomy rate was 31%. At 3 years after diagnosis, the capacity to work including those with colectomy was not different from that of the general population. The study also indicated that, at any given time, 50% of those with UC were without symptoms, 30% had low disease activity, and 20% had moderate to high disease activity. Within 10 years of diagnosis, 97% of patients experienced at least one relapse. References Hendriksen C, Kreiner S, Binder V. Long term prognosis in ulcerative colitis based on results from a regional patient group from the county of Copenhagen. Gut 1985; 26:158-163.

    46. Simptomi i znaci ulceroznog kolitisa: Mayo Score (CAI) Ucestalost stolica 0 (normalno) do 3 (5 ili vie iznad normalnog ) Krvarenje iz rektuma 0 (bez krvi) do 3 (cista krv) Nalazi fleksibilne sigmoidoskopije 0 (normalno) do 3 (teka aktivna bolest) Opci pregled lijecnika 0 (normalno) do 3 (teka bolest)

    47. Hanauer SB. N Engl J Med 1996;334(13):841-848. Ocjena aktivnosti ulceroznog kolitisa Slide 7 In patients with UC, disease activity is assessed primarily on the basis of clinical features most often using the criteria of Truelove and Witts. These criteria are clinically useful, although many patients have features that fall between those classified as mild and those classified as severe. Disease activity can also be assessed endoscopically. The histologic findings loosely parallel the endoscopic features. References Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996;334(13):841-848.Slide 7 In patients with UC, disease activity is assessed primarily on the basis of clinical features most often using the criteria of Truelove and Witts. These criteria are clinically useful, although many patients have features that fall between those classified as mild and those classified as severe. Disease activity can also be assessed endoscopically. The histologic findings loosely parallel the endoscopic features. References Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996;334(13):841-848.

    48. The therapeutic pyramid is based upon clinical trials that have evaluated single agents for specified disease activity.The therapeutic pyramid is based upon clinical trials that have evaluated single agents for specified disease activity.

    49. Note: In mild or moderate UC, the patients with limited (left-sided UC and proctitis) disease can also be treated with local enemas: 5-ASA and/or CS.Note: In mild or moderate UC, the patients with limited (left-sided UC and proctitis) disease can also be treated with local enemas: 5-ASA and/or CS.

    50. Note: In mild or moderate UC, the patients with limited (left-sided UC and proctitis) disease can also be treated with local enemas: 5-ASA and/or CS.Note: In mild or moderate UC, the patients with limited (left-sided UC and proctitis) disease can also be treated with local enemas: 5-ASA and/or CS.

    51. Truelove: The calculation of the patients in the 1954 study by Truelove et al are is excluding the severe UC pts only the Mild to Moderate UC patients are included in the calculation above. Patients in the Truelove study were treated with various doses of oral steroids. For remission all criteria below must be met: One or two stools a day without blood, No fever, No tachycardia, ESR normal or returning to normal, Gaining weight Fabion: Patients Faubion 2001: Retrospective review of pts treated with CS (oral or iv, most oral). 77% on 5-ASA, none on AZA. Definitions (Faubion 2001): Complete remission: defined as total regression of clinical symptoms (#2 bowel movements/day; no blood, pus, or mucus in feces; and no abdominal pain, fever, weight loss, or extraintestinal symptoms). Partial clinical remission: regression of clinical symptoms (#4 stools/day; blood, pus, mucus in feces; or abdominal pain; or all 4 less than daily and no systemic symptoms, such as fever or weight loss). 3. No response: no regression of clinical symptoms. CS Therapy In most patients, CS therapy was administered as oral prednisone. The initial prednisone doses ranged from 40 to 60 mg/day, and individual treating physicians attempted prednisone taper over a variable period of 36 months. Truelove: The calculation of the patients in the 1954 study by Truelove et al are is excluding the severe UC pts only the Mild to Moderate UC patients are included in the calculation above. Patients in the Truelove study were treated with various doses of oral steroids. For remission all criteria below must be met: One or two stools a day without blood, No fever, No tachycardia, ESR normal or returning to normal, Gaining weight Fabion: Patients Faubion 2001: Retrospective review of pts treated with CS (oral or iv, most oral). 77% on 5-ASA, none on AZA. Definitions (Faubion 2001): Complete remission: defined as total regression of clinical symptoms (#2 bowel movements/day; no blood, pus, or mucus in feces; and no abdominal pain, fever, weight loss, or extraintestinal symptoms). Partial clinical remission: regression of clinical symptoms (#4 stools/day; blood, pus, mucus in feces; or abdominal pain; or all 4 less than daily and no systemic symptoms, such as fever or weight loss). 3. No response: no regression of clinical symptoms. CS Therapy In most patients, CS therapy was administered as oral prednisone. The initial prednisone doses ranged from 40 to 60 mg/day, and individual treating physicians attempted prednisone taper over a variable period of 36 months.

    52. Bolesnici s akutnim, tekim ulceroznim kolitisom lijeceni steroidima

    53. Odgovor na primjenu CsA u akutnom, tekom UK One additional elective surgery in CsA 5/9 stable placebo all responded to open label CSA One additional elective surgery in CsA 5/9 stable placebo all responded to open label CSA

    54. Ucestalost kolektomija u bolesnika s tekim akutnim UK nakon 3 mjeseca lijecenja i uz primjenu jedne infuzije infliksimaba Note: One infusion only. Infliximab as Rescue Therapy in Severe to Moderately Severe Ulcerative Colitis: A Randomized, Placebo-Controlled Study GUNNAR JRNEROT, Gastroenterology 2005; 128:1805 Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 68 if they fulfilled index criteria on day 57 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P .017; odds ratio, 4.9; 95% confidence interval, 1.4 17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 45 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment. Note: One infusion only. Infliximab as Rescue Therapy in Severe to Moderately Severe Ulcerative Colitis: A Randomized, Placebo-Controlled Study GUNNAR JRNEROT, Gastroenterology 2005; 128:1805 Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 68 if they fulfilled index criteria on day 57 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P .017; odds ratio, 4.9; 95% confidence interval, 1.4 17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 45 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

    55. Kirurki zahvat u bolesnika s UK: indikacije

    56. Klinicki odgovor i odravanje remisije u bolesnika s UK primjenom infliksimaba Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis Paul Rutgeerts, William J. Sandborn, et al., N Engl J Med 2005;353:2462-76. background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor a, is an established treatment for Crohns disease but not ulcerative colitis. methods Two randomized, double-blind, placebo-controlled studies the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P=0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). conclusions Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.) Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis Paul Rutgeerts, William J. Sandborn, et al., N Engl J Med 2005;353:2462-76. background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor a, is an established treatment for Crohns disease but not ulcerative colitis. methods Two randomized, double-blind, placebo-controlled studies the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P=0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). conclusions Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

    57. Cijeljenje sluznice uz redovitu primjenu infliksimaba u 8., 30. i 54. tjednu Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis Paul Rutgeerts, William J. Sandborn, et al., N Engl J Med 2005;353:2462-76. background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor a, is an established treatment for Crohns disease but not ulcerative colitis. methods Two randomized, double-blind, placebo-controlled studies the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P=0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). conclusions Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.) Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis Paul Rutgeerts, William J. Sandborn, et al., N Engl J Med 2005;353:2462-76. background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor a, is an established treatment for Crohns disease but not ulcerative colitis. methods Two randomized, double-blind, placebo-controlled studies the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P=0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). conclusions Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

    58. Unapredivanje kvalitete ivota bilo je znacajno bolje u skupini lijecenoj infliksimabom

    59. Zakljucak: infliksimab u bolesnika s UK Djelotvorno Inducira i odrava remisiju Cijeli sluznicu crijeva Smanjuje potrebu za steroidima (doza/vrijeme) Povecava kvalitetu ivota bolesnika Smanjuje ucestalost hospitalizacija povezanih s osnovnom bolecu

    60. CROHNOVA BOLEST PRIKAZ SLUCAJA NA TERAPIJI INFLIXIMABOM

    61. PODACI O BOLESNIKU bolesnik je 44. godinji muakarac koji boluje od Crohnove bolesti zadnjih 9 godina bez drugih bolesti, ne pui i ne konzumira alkohol terapija: Imuran, Medrol i Pentaza

    62. u svibnju 2009. god. se javlja enterokutana fistula kao komplikacija osnovne bolesti prisutna opca slabost, anemija sa potrebom za transfuziju E (ordinirano 690 ml depleciranih E) , hipoalbuminemija, povieni upalni parametri, gubitak na tjelesnoj teini od 4 kg zadnjih par mjeseci

    63. Rtg gastroduodenuma sa pasaom crijeva i CT nalaz: enterokutana fistula 07. svibnja se ordinira prvi ciklus Infliximaba 300 mg uz profilaksu Medrolom 80 mg Nastavak terapije: Imuran tbl 50 mg 2x1, Penatasa 500 mg 3x2 tbl, Ciprofloxacin 500 m, 2xl, Metronidazol 250 mg, 3xl Prolife tbl 2x1, Feroglobin B12 1x1, dijeta.

    64. Drugi ciklus Infliximaba 300 mg se ordinira nakon 2 tjedna Treci ciklus istom dozom Infliximaba se ordinira 03 srpnja/09 Cetvrti ciklus se ordinira 27. kolovoza/09

    65. Na ordiniranu terapiju dolazi do potpunog zatvaranja enterokutane fistule uz poboljanje opceg stanja bolesnika Korigiranje anemije, hipoalbuminemije i smirivanja parametara upale

    66. Usporedba laboratorijskih nalaza prije terapije Infliximabom (A) i na zadnjoj kontroli (B) nakon 3 mjeseca Opce dobro stanje i kvalitete ivota

    67. Nastavak terapije: Imuran tbl 50 mg 1x1, Pentasa 500 3x2 tbl, Prolife tbl 2x1, dijeta. Slijedeca terapija za 8 tjedana Koliko dugo primati terapiju ?

    68. HVALA NA POZORNOSTI

More Related