Inflammatory bowel disease: pathogenetic mechanisms

Abstract Significant progress has been made in the understanding of ulcerative colitis and Crohn's Disease over the last decades.Despite this, the pathogenesis of inflammatory bowel disease (IBD) remains obscure, especially at molecular level. Various contributing factors have been identified so far, but their respective contributions are not entirely clear cut. In this review, we focus on the genetic and environmental factors linked with IBD pathogenesis. We also explore the role of pro-inflammatory cytokines on the molecular pathophysiology of IBD

Treatment of refractory left sided ulcerative colitis : lessons from the sages IBD registry

Background: Left sided ulcerative colitis is often a severe disease which requires aggressive medical therapy. Rarely, it can result in colectomy. Moreover, it can progress and extent to involve the entire colon. Method: Retrospective analysis of patient data on the SAGES IBD database. Patient data with severe left sided ulcerative colitis requiring anti-TNF therapy for the period between September 2016 to August 2017. Patient consent was obtained. Results: A total of 149 requests for biologic therapy were received during this period of which 13 had left sided ulcerative colitis. Seven (53.4%) were male and the mean age at diagnosis 33.3 years. Mean age at commencement of biologic therapy was 40.9 years. There were no smokers. One (7.7%) had ulcerative proctitis, 7 (53.8%) had proctosigmoiditis and 5 (38.4%) had left sided colitis. No patient was receiving topical steroids and 2 (15.4%) patients had exposure to topical 5-aminosalicylic acid. All patients had exposure to oral 5-aminosalicylic acid and 9 (69.2%) were receiving ongoing treatment. Ten (76.9%) received azathioprine or 6-mercaptopurine and 5 (38.5%) received methotrexate. Of the 12 patients on immunomodulator therapy, 10 (76.9) were concurrently on 5-aminosalicylic acid. Seven (53.8%) patients received infliximab and 9 (69.2%) patients received adalimumab. No one received golimumab or vedolizumab. All patients received standard dose anti-TNF therapy except 1 (7.7%) patient who received double dose infliximab. Biologic therapy was well tolerated with good clinical outcome and no side-effects. Conclusion: The incidence of severe left sided ulcerative colitis was low in this cohort. Severe left sided disease is associated with a high medication burden and cost. Response to biologic therapy was excellent

Treatment of refractory left sided Ulcerative colitis: lessons from the Sages IBD registry

ABSTRACT Background: Left sided ulcerative colitis is often a severe disease which requires aggressive medical therapy. Rarely, it canresult in colectomy. Moreover, it can progress and extent to involve the entire colon. Method: Retrospective analysis of patient data on the SAGES IBD database. Patient data with severe left sided ulcerative colitis requiring anti-TNF therapy for the period between September 2016 to August 2017. Patient consent was obtained. Results: A total of 149 requests for biologic therapy were received during this period of which 13 had left sided ulcerative colitis. Seven (53.4%) were male and the mean age at diagnosis 33.3 years. Mean age at commencement of biologic therapy was 40.9 years. There were no smokers. One (7.7%) had ulcerative proctitis, 7 (53.8%) had proctosigmoiditis and 5 (38.4%) had left sided colitis. No patient was receiving topical steroids and 2 (15.4%) patients had exposure to topical 5-aminosalicylic acid. All patients had exposure to oral 5 aminosalicylic acid and 9 (69.2%) were receiving ongoing treatment. Ten (76.9%) received azathioprine or 6-mercaptopurine and 5 (38.5%) received methotrexate. Of the 12 patients on immunomodulator therapy, 10 (76.9) were concurrently on 5-aminosalicylic acid. Seven (53.8%) patients received infliximab and 9 (69.2%) patients received adalimumab. No one received golimumab or vedolizumab. All patients received standard dose anti-TNF therapy except 1 (7.7%) patient who received double dose infliximab. Biologic therapy was well tolerated with good clinical outcome and no side-effects. Conclusion: The incidence of severe left sided ulcerative colitis was low in this cohort. Severe left sided disease is associated with a high medication burden and cost. Response to biologic therapy was excellent

Golimumab treatment in South African IBD patients: A 2 year review

Background: Ulcerative colitis (UC) is a chronic relapsing inflammation of the colon that sometimes fails standard medicaltherapy. Escalation of treatment often requires introduction of anti-TNF therapy. Golimumab is a new anti-TNF agent launched in South Africa in 2015 for moderate-severe UC. It is not licensed for Crohn's disease (CD).Method: Retrospective analysis of patients with moderate-severe UC requiring golimumab therapy (induction and maintenance therapy) for a 2-year period from September 2016 to August 2018 on the SAGES IBD registry. Patients gave signed informed consent.Results: A total of 109 patients required induction therapy with biologics during this 2 year period of which 12 (11%) required golimumab. A further 4 patients were already receiving golimumab making it 16 patients in total. Fourteen (87.5%) patients had UC and 2 (12.5%) had CD. Ten (62.5%) of the 16 patients were female with a median age of 46. There was 1 current smoker. A small number (18.8%) were taking corticosteroids at the time of induction with golimumab but they all discontinued steroid therapy during golimumab treatment. All 14 patients with UC was currently or previously exposed to aminosalicylates.Four (28.5%) of them discontinued this treatment due to intolerance or lack of efficacy. None of the patients with CD received aminosalicylates. Fourteen (87.5%) of the 16 patients received immunomodulator therapy. Four (28.5%) patients discontinued this treatment because of side-effects or lack of effect. Eleven (68.8%) patients received both aminosalicylates and immunomodulatory therapy concurrently during the study period. Ten (62.5%) of the 16 patients were naïve to biologics and were commenced on golimumab as first line therapy. Nine (90%) of the 10 patients remained on golimumab for the entire duration of the study. Six (37.5%) patients were switched to golimumab after having failed other forms of biologic therapy. Two (12.5%) patients stopped treatment with golimumab altogether during the study period because of treatment failure. Golimumab was well tolerated with good clinical outcome and no side-effects.Conclusion: The use of golimumab for moderate-severe IBD remained low since its launch. Golimumab therapy was safe and effective in moderate-severe UC and CD, although patient numbers were low. Treatment failure rate was low