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Therapy in inflammatory bowel disease
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis is to study treatment of inflammatory bowel disease with respect to an acute severe attack of ulcerative colitis and endoscopic balloon dilation in stricturing Crohn’s disease.

A retrospective follow-up was made in 158 patients who were given intensive intravenous corticosteroid treatment due a severe, moderate, or mild attack of ulcerative colitis between 1975 and 1982. After 10 years, the colectomy frequency in the severe disease group was 64%, and 49% and28% in the moderate and mild groups, respectively. Severity of the original attack did not influence the subsequent clinical course with respect to colectomy.

In 2005, a controlled Swedish–Danish trial of infliximab as rescue therapy in an acute severe attack of steroid refractory ulcerative colitis showed that colectomy frequencies after 3 months were lower in infliximab-treated patients (29%) compared to placebo-treated patients (67%). After 3 years, a statistically significantly lower colectomy frequency remained in patients treated with infliximab (50%) compared to placebo (76%).

Between 1989 and 2009, 178 patients underwent endoscopic balloon dilation due to intestinal strictures in Crohn’s disease. Seventy-five patients,with a follow-up of 5 years or longer, underwent dilations due to symptomatic strictures only. After 5 years of follow-up, 39/75 (52%) of the patients had undergone no further intervention or one additional dilation only, and 36% had had surgery. The complication frequency was 5.3%, of which 10 patients (1.3%) required surgery. In 83 patients, we studied whether smoking at diagnosis affected the outcome after index dilation. In the group of active smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) in never smokers (HR 2.18, 95% CI: 1.22-3.93,p = 0.01). Clinical parameters such as sex, age at diagnosis, age at first dilation, balloon size, localisation of stricture, treatment with azathioprine and treatment period did not influence outcome.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , 97 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 75
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-25599ISBN: 978-91-7668-897-7 (print)OAI: oai:DiVA.org:oru-25599DiVA: diva2:548433
Public defence
2012-11-23, Wilandersalen, Universitetssjukhuset (USÖ), Örebro, 09:00 (Swedish)
Opponent
Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2016-04-20Bibliographically approved
List of papers
1. Long-term colectomy rate after intensive intravenous corticosteroid therapy for ulcerative colitis prior to the immunosuppressive treatment era
Open this publication in new window or tab >>Long-term colectomy rate after intensive intravenous corticosteroid therapy for ulcerative colitis prior to the immunosuppressive treatment era
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2007 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 102, no 11, 2513-2519 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Corticosteroids are a cornerstone in the treatment of a severe attack of ulcerative colitis (UC). The long-term prognosis in this patient group is not well described. We studied the long-term colectomy and relapse rates in patients given intensive intravenous corticosteroid treatment (IIVT) for acute UC. METHODS: A retrospective clinical study of 158 patients with UC treated in 1975-1982 with IIVT. Patients were followed-up to death, colectomy or last visit. RESULTS: A total of 11 patients were excluded due to change of diagnosis (N = 10) or lost to follow-up (N = 1). The indication for index IIVT in the remaining 147 patients was a severe attack (N = 61), a moderately severe attack (N = 45), a mild attack (N = 29) or chronic continuous disease (N = 12). The median (range) duration of follow-up was 173 (4-271) months in patients escaping colectomy during the first 3 months. Three months after IIVT, the colectomy rates were 28/61 (46%) in a severe attack, 4/45 (9%) in a moderately severe, and 1/29 (3%) in a mild attack. After 10 yr, the colectomy rates were 39/61 (64%), 22/45 (49%), and 8/29 (28%), respectively. During follow-up, neither colectomy incidence beyond 3 months, time to first relapse nor relapse incidence was influenced by severity of initial attack, except for a lower relapse incidence after a severe attack. CONCLUSIONS: In patients escaping colectomy during the first 3 months after IIVT, the future prognosis was similar irrespective of initial disease severity.

Place, publisher, year, edition, pages
New York: American College of Gastroenterology, 2007
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-11550 (URN)10.1111/j.1572-0241.2007.01435.x (DOI)17680849 (PubMedID)
Available from: 2010-08-11 Created: 2010-08-11 Last updated: 2015-06-09Bibliographically approved
2. Clinical trial: colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
Open this publication in new window or tab >>Clinical trial: colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
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2010 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 32, no 8, 984-989 p.Article in journal (Refereed) Published
Abstract [en]

Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

National Category
Medical and Health Sciences Clinical Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12877 (URN)10.1111/j.1365-2036.2010.04435.x (DOI)000282221200004 () 20937043 (PubMedID)
Available from: 2011-01-05 Created: 2011-01-03 Last updated: 2017-02-13Bibliographically approved
3. Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn's disease
Open this publication in new window or tab >>Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn's disease
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2012 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 36, no 2, 151-158 p.Article in journal (Refereed) Published
Abstract [en]

Background: Bowel strictures are a major cause of morbidity, hospitalisation and surgery in Crohn's disease.

Aim: We report short- and long-term efficacy and safety of endoscopic balloon dilation of strictures due to Crohn's disease.

Methods: Retrospective study of patients who underwent endoscopic balloon dilation between 1987 and 2009.

Results: We performed 776 dilations, of which 621 (80%) were on anastomotic strictures, in 178 patients (94 women) with Crohn's disease. At first dilation, median (IQR) age of patients was 45 (37-56) years and disease duration 16 (8-22) years. Technical success rate was 689/776 (89%). A subset of 75 patients from the primary catchment area, with >5-year follow-up, underwent a total of 246 dilations. At 1-year follow-up, 60/75 (80%) patients had undergone no further intervention or one additional dilation only. At 3 and 5 years, corresponding figures were 43/75 (57%) and 39/75 (52%). Cumulative proportions of patients undergoing surgery at 1, 3 and 5 years were 13%, 28% and 36%. Complication rate per procedure for all 178 patients was 41/776 (5.3%), bowel perforation (n = 11, 1.4%), major bleeding requiring blood transfusion (n = 8, 1.0%), minor bleeding (n = 10, 1.3%) and abdominal pain or fever (n = 12, 1.5%). Ten patients underwent surgery due to complications (perforation n = 8, bleeding n = 2). There was no procedure-related mortality.

Conclusion: Endoscopic balloon dilation is an efficacious and safe alternative to surgical resection of intestinal strictures in Crohn's disease. At 5-year follow-up, 52% of patients required no further or one additional dilation only, whereas 36% had undergone surgical resection. Complication frequency was low.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2012
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-24220 (URN)10.1111/j.1365-2036.2012.05146.x (DOI)000305329000008 ()22612326 (PubMedID)2-s2.0-84862508948 (Scopus ID)
Note

Funding Agencies:

Foundation for Clinical Research in Inflammatory Bowel Disease, United States 

Uppsala-Örebro Regional Research Council, Sweden 

Available from: 2012-08-03 Created: 2012-08-03 Last updated: 2017-03-26Bibliographically approved
4. Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn’s disease
Open this publication in new window or tab >>Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn’s disease
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Endoscopic balloon dilation is an efficacious and safe alternative to surgery as treatment of short intestinal strictures in Crohn’s disease (CD). Factors predicting outcome of the procedure are not well described.

Aim: To evaluate whether smoking at diagnosis, treatment with azathioprine, or other clinical variables may affect clinical outcome after endoscopic dilation.Endpoint was requirement of a new intervention such as dilation or surgerywith intestinal resection or strictureplasty.

Methods: Retrospective study of 83 patients with CD who underwent endoscopic balloon dilation of an intestinal stricture between 1987 and 2009.

Results: After index dilation 55/83 patients underwent a new intervention. Among current smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) among never smokers (HR 2.18, 95%CI 1.22-3.93, P=0.009). After 5 years, cumulative probability of new intervention was 0.81 in smokers compared to 0.52 in never smokers; difference 0.29 (95 % CI 0.07–0.52, P = 0.01). In 16 patients, therapy with azathioprine was initiated before or shortly after the index dilation; 7/16 underwent a new intervention compared to 48/67of those without azathioprine (HR 0.46, 95%CI 0.21-1.03, P=0.06). After adjustment for other variables, the association was even weaker (HR 0.80, 95%CI 0.29-2.18, P=0.668). Sex, age atdiagnosis, age at first dilation, balloon size, location of stricture, and treatment period did not influence outcome.

Conclusions: Smoking doubles the risk of recurrent stricture formation requiring a new intervention after index dilation. Maintenance therapy with azathioprine did not influence the subsequent course and need for a new intervention.

Keyword
Crohn's disease, ulcerative colitis, rescue therapy, infliximab, stricture, endoscopic balloon dilation, smoking, surgery
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26344 (URN)
Note

Other affiliations:

Anders Gustavsson 1,2,  JonasHalfvarson 1, Curt Tysk 1.

1) Department of Medicine, Division of Gastroenterology, Örebro University Hospital

2) Department of Internal Medicine, Karlstad Hospital, Karlstad, Sweden

Available from: 2012-10-29 Created: 2012-10-29 Last updated: 2016-12-06Bibliographically approved

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