Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn^®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity.</p> <p>Methods</p> <p>Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months.</p> <p>Results</p> <p>Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time.</p> <p>Conclusions</p> <p>IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.</p

Ulcerative colitis and cancer with special reference to the increased colorectal cancer risk

The association between ulcerative colitis (UC) and cancer in a defined geographical region in Sweden was analyzed. UC patients have an increased overall risk of cancer of 40%, mainly due not only to the well-known increased risk of colorectal cancer (CRC) but also to the risk of hepatobiliary cancer associated with primary sclerosing cholangitis (PSC). The overall risk is partly counterbalanced by a decreased risk of lung cancer, reflecting the observation that there is a larger proportion of nonand ex- smokers among UC patients than among the general population. A 23-year prospective study to evaluate the safety, reliability, and efficacy of a prospective colonoscopic surveillance program in long-standing UC was analyzed, and estimates of the cumulative risks of developing histologic dysplasia and gross chromosomal abnormalities (DNA aneuploidy) were calculated. A theoretical modified algorithm for separation of low-risk from high-risk cancerprone UC patients early was designed, in order to minimize surveillance efforts and costs. The cumulative risk of having >= low-grade dysplasia at least once after 25 years of disease was 16%, and for DNA aneuploidy it was 29%. Patients with three consecutively negative colonoscopies could be put into a low- risk group in which surveillance could be decreased to colonoscopy every fifth year. Combining histopathology with DNA analyses allows a schedule sufficiently accurate for selection of high-risk patients and also has the potential to reduce the number of colonoscopies by 30%. Colonoscopic surveillance with biopsies for histological assessment and DNA flow cytometry is a reliable and safe way to select high-risk UC patients for prophylactic colectomy. The reproducibility of DNA aneuploidy from one examination to another in a surveillance program for UC was determined, as was the topographical correlation between the aneuploid peaks and histological dysplasia in the colon and rectum. Detection of DNA aneuploidy in UC patients is persistent and reproducible and is closely related to and often precedes histological dysplasia. Widespread aneuploidy indicates that the entire colorectal mucosa is at increased risk of malignant transformation. The relationship between the mucin-associated carbohydrate antigen Sialyl-Tn (STn) and DNA aneuploidy with respect to topographic and temporal distribution in the colon and to areas with dysplasia was analyzed. STn antigen and DNA aneuploidy are independent markers of neoplastic transformation. Determination of STn expression may complement dysplasia and DNA aneuploidy in identifying risk for colonic neoplasia in UC. To analyze the impact of colonoscopic surveillance on CRC mortality in patients with UC, a nested case-control study was performed using observational data from a large population-based cohort of patients with UC. Two out of 40 cases and 18 out of 102 controls had received at least one surveillance colonoscopy [relative risk (RR)=0.29, 95% confidence interval (CI) 0.06-1.31 ]. Twelve of the controls but only one of the cases had been subjected to two or more surveillance colonoscopies (RR=0.22, 95% CI 0.03-1.74), thus indicating a protective dose-response relationship. Colonoscopic surveillance may be associated with a decreased risk of death from colorectal cancer in patients with long- standing ulcerative colitis

Kolitcancer - mer myt än verklighet?

Patients with ulcerative colitis (UC) and Crohn´s colitis are at increased of developing colorectal cancer (CRC). However, recent studies suggest that the risk is now less than previously thought. Well established risk factors include extent and duration of disease, primary sclerosing cholangitis (PSC) and a family history of CRC. Recently inflammation (both microscopic and macroscopic) has been shown to represent an important independent risk factor for CRC development. Thus one likely explanation for the decreased risk of CRC observed in UC patients is the use of agents that inhibit the inflammatory process, particularly 5-ASA. Ursodeoxycholic acid has been found to be chemopreventive in UC patients with PSC. Evidence from case series and case-control studies suggest that surveillance colonoscopy also reduces the risk of CRC. Prospective randomized controlled trials will never be done because of ethical and logistical concerns. Thus, in the absence of these studies, our knowledge will have to rely on biologic and observational studie

Use of complementary and alternative medicine in Swedish patients with inflammatory bowel disease : a controlled study.

BACKGROUND: There is an increasing interest in complementary and alternative medicine (CAM) in patients with chronic diseases, including those with inflammatory bowel disease (IBD). Patients may turn to CAM when conventional therapies are inadequate or associated with side effects for symptomatic relief or to regain control over their disease. The objectives were to explore CAM use and perceived effects in IBD patients in comparison with a control group. METHODS: A cross-sectional, multicenter, controlled study was carried out. IBD patients were invited from 12 IBD clinics in Sweden. Controls were selected randomly from a residence registry. A study-specific questionnaire was used for data collection. RESULTS: Overall, 48.3% of patients with IBD had used some kind of CAM during the past year compared with 53.5% in controls (P=0.025, adjusted for age, sex, geographic residence, and diet). The most frequently used CAM among IBD patients was massage (21.3%), versus controls (31.4%) (adjusted P=0.0003). The second most used CAM was natural products, 18.7% in IBD patients versus 22.3% of the controls (unadjusted P=0.018). In all, 83.1% of the patients experienced positive effects from CAM and 14.4% experienced negative effects. CONCLUSION: Overall, 48.3% of Swedish IBD patients used some kind of CAM and controls used CAM significantly more. Natural products were used by one-fifth of the patients and even more by controls. This is notable from a patient safety perspective considering the possible risks of interactions with conventional medication. In all, 40% of the patients reported adverse events from conventional medicine. Patients experienced predominantly positive effects from CAM, and so did controls

Clinical effectiveness of golimumab in ulcerative colitis : a prospective multicentre study based on the Swedish IBD Quality Register, SWIBREG

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore &amp;gt;= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by &amp;gt;= 3 points or 30% from baseline) and remission (defined as a Mayo score of &amp;lt;= 2 with no individual subscores &amp;gt;1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p &amp;lt; .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p &amp;lt; .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]</p