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Case report

Cristina Radu


 

I.M., 39 yrs, female Urban Non-smoker, no alcohol use

stricture of the anal channel – digitally dilated in Jan 2009 .stricture of the sigmoid colon – endoscopic dilation in Jan 2009 ■Perianal fistula ■Erythema nodosum – May 2009  .Personal History Nonspecific Inflammatory Bowel Disease since 1995  Colonic Crohn’s Disease – stenosing and fistulising pattern since 2007 .

WBC=5150/mm3) ▪ mild secondary anemia (HGB=9. diurnal. no blood Physical examinaton ▪ normal weight ▪ perianal fistulous orifice Biological examination ▪ inflammatory syndrome (fibrinogen=660mg/dl. MCV=73fl. MCHC=30.September 2009 Symptoms ▪ 4 loose stools/day.9g/dl.3g/dl) .

i. Which therapy should we choose next? .d.Treatment so far    Multiple applications of systemic corticosteroids Maintenance treatment with Azathioprine 125 mg/day (2.5mg/kgc/day) since May 09 Ciprofloxacin 500 mg b.

or with systemic corticosteroids  For those who have relapsed. or. if intolerant. although surgical options should also be considered  . methotrexate should be considered Infliximab should be considered in addition for corticosteroid or immunomodulator refractory disease or intolerance.ECCO Statement 5D  Active colonic CD may be treated with sulfasalazine if only mildly active. azathioprine or mercaptopurine should be added.

09 and 05. (21.v.11 – admission for perianal pain (48 hrs history) Biological examination: ▪ mild secondary anemia (HGB=9.10) 03.8g/dl MCHC=32.Evolution    Two Infliximab applications 5mg/kgc i.3g/dl) ▪ inflammatory syndrome (fibrinogen=582mg/dl) .

Colonoscopy      Perianal fistulous orifice & perianal induration Stricture of the anal channel – digitally dilated Inflammatory stricture at 40cm Cobblestone aspect Perforation risk .

Pelvic CT scan   Inflammatory signs – wall of the rectum. edema) Small perirectal and perineal abscesses (17/26mm) with associated fibrosis . sigmoid and descendent colon (thickening.



i.i.d. and Metronidazole 250mg t.v.) Azathioprine 125mg/day Ciprofloxacin 500mg b.d.Treatment      Surgical drainage Temporization of the biological therapy Initiation of CS therapy (MTP 40mg/day i. .

normal consistency Biological tests: mild anemia (Hb=10.6g/dl). inflammatory syndrome in remission (fibrinogen=) Colonoscopy: complex perianal fistula. 3 stools/day. no strictures)    Surgical consult: no signs of local inflammation or perianal abscesses . diurnal. mild Crohn’s disease lesions (pseudopolips.Reevaluation after one month  Clinical examination: normal weight.


i.d Third Infliximab application (15. t.12 10 wks after the second one) .Treatment     Oral CS Azathioprine 125mg/day Metronidazole 250mg.

The role of biological agents in Crohn’s disease therapy       Rapid induction and long-term maintenance of clinical and endoscopic remission in luminal and fistulising forms Maintenance of remission without CS Control of extraintestinal manifestations Avoidance of hospitalization and surgery Decrease in complications rate QOL improvement .

humanized recombinant antibody to TNF-α Certolizumab pegol .Fab fragment of a humanized antiTNF-α monoclonal antibody Natalizumab – anti-α4-integrin monoclonal antibody .Available biological agents     Infliximab .mouse-human chimeric monoclonal antibody to TNF-α Adalimumab .

Indications of Infliximab Therapy for IBD     Moderately to severely active luminal Crohn’s disease → induction and maintenance of remission Active fistulizing Crohn’s disease → induction and maintenance of remission UC Crohn’s disease in children .

TNF-α effects       macrophage activation (autocrine) induction of proinflammatory cytokines IL1 and IL6 induction of cell adhesion molecules procoagulant granulocytes activation and degranulation production of MMP. direct tissue injury .

Infliximab efficiency  ACCENT1: maintenance infliximab therapy in patients with active Crohn’s disease – 39 to 45% of pts treated with infliximab who had an initial response (wk 2) maintained remission after 30 weeks vs 21% on placebo – Mean maintenance of remission was 38 to 54 weeks compared with 21 weeks for patients who received placebo treatment  ACCENT2: maintenance infliximab therapy in patients with abdominal or perianal fistulas – At week 54. as compared with 19% of patients in the placebo maintenance group . 36% of patients in the infliximab maintenance group had a complete absence of draining fistulas.

consideration may be given to treatment with 10 mg/kg . 2 and 6 weeks (2 hrs infusion) maintenance regimen of 5 mg/kg every 8 weeks for adult patients who respond and then lose their response.Dosage and administration    5 mg/kg given as an intravenous induction regimen at 0.

Antibodies to Infliximab      The incidence of antibodies to infliximab in patients given a 3-dose induction regimen followed by maintenance dosing was approximately 10% A higher incidence of antibodies in Crohn’s disease pts after drug free intervals >16 weeks The majority of antibody-positive patients had low titers Patients who were antibody positive were more likely to have higher rates of clearance. reduced efficacy and to experience an infusion reaction Antibody development was lower among pts receiving immunosuppressant therapies .

and pruritus .headache. paracetamol. and sometimes corticosteroids .generally seen after one to five maintenance infusions . nausea. dizziness. injection-site irritation. flushing. chest pain. dyspnea.Adverse effects 1) Infusion reactions (6%) .the lowest incidence occurred among patients receiving both steroids and immunosuppressives .respond to slowing the infusion rate or treatment with antihistamines.16% among patients positive for antibodies to infliximab .

Adverse effects 2) A delayed reaction of joint pain and stiffness. . especially if there has been an interval more than one year after a previous infusion. fever. myalgia and malaise may occur. Pre-treatment with hydrocortisone is advised in these circumstances.

PPD skin test.Adverse effects 3) Infections (36%) .severe infections (4%): pneumonia. abscess.screening for infections: CBC.most frequent: upper respiratory tract infections and urinary tract infections . antiHBc. sepsis . anti-HBs. AgHBs. cellulitis. PCR. anti-HIV . anti-HCV. chest X-ray. skin ulceration.

et al. 104:1575 . Am J Gastroenterol 2009 (clinical review).Latent TB     Chemoprophylaxis with hydrazide 300mg/day (5mg/kgc/day) Maximum benefit – 9 months Clinical practice – 6-9 months Initiation of chemoprophylaxis one month before IFX therapy begins Papa A.

Nat Clin Pract Gastroenterol Hepatol 2007. Am J Gastroenterol 2008.Adverse effects 4) Autoantibodies/Lupus-like Syndrome .conflicting data concerning LMNH risk . et al. 103: S436 .anti-dsDNA (34%) and ANA (56%) . 4: 78 Lichtenstein GR et al.very rare lupus-like syndrome 5) Malignancies .hepato-splenic T-cell lymphoma in young IBD pts treated with IFX and thiopurines (16 cases) 6) Heart failure agravation Biancone cause-effect association between IFX and global cancer risk in IBD pts .

uterine cervical dysplasia .Contraindications      severe infections (TB or others) pregnant or nursing women moderate to severe congestive heart failure solid and hematological tumors with evolving potential in the past 5 yrs (absolute) premalignant conditions (colonic and urinary polyps. myelodysplasia.relative) .

therefore screening for infection is of critical importance .Conclusions    Indications for Infliximab in Crohn’s disease include moderate to severe active luminal or fistulous disease Infliximab proved to be an efficient treatment under these conditions The main concern during therapy is the risk of infection.