Juha Kuisma

Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora

Background : Preliminary trials of probiotics in preventing recurrent chronic pouchitis have been encouraging.

Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD

BACKGROUND AND AIMS Deep remission, meaning clinical remission with mucosal healing (MH), with anti-tumor necrosis factor-alpha (TNF-α) agents is a new target for therapy in inflammatory bowel disease (IBD). Our aim was to study how often patients on TNF-α blocking therapy actually achieve deep remission. METHODS The total of 252 IBD patients retrospectively included (183 Crohns disease (CD), 62 ulcerative colitis (CU) or 7 inflammatory bowel disease unclassified-type colitis (IBDU)) received TNFα-antagonists (177 infliximab, 75 adalimumab) for at least 11 months and underwent ileocolonoscopy. We reviewed endoscopic and histological findings, clinical symptoms, C-reactive protein (CRP), and fecal calprotectin (FC) levels, and data on TNF-α blocking therapy. Defining deep remission as no clinical symptoms with endoscopic remission (the simple endoscopic score for Crohns disease, SES-CD 0-2 or Mayo endoscopic subscore 0-1). RESULTS Of the 252 patients, 168 (67%) were in clinical remission and 122 (48%) in deep remission after a median of 23 months of maintenance therapy. Of the 183 CD patients, 117 (64%) reached clinical remission and 79 (43%) deep remission. Of the UC patients, 52 (75%) were in clinical remission and 43 (62%) in deep remission. The majority of patients in deep remission (n=99, 81%) also had histologically inactive disease. Both median CRP and FC levels were significantly lower in patients with deep remission. CONCLUSION Reassuringly, half of the IBD patients on the TNFα-blocking maintenance therapy achieved deep remission. The majority of patients in deep remission also achieved histological remission.

Does Fecal Calprotectin Predict Short-Term Relapse After Stopping Tnfα-Blocking Agents In Inflammatory Bowel Disease Patients In Deep Remission?

BACKGROUND AND AIMS This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk. METHODS We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 μg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse. RESULTS Of 52 enrolled patients, 49 (16 Crohns disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission. CONCLUSION FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

Long term metabolic consequences of ileal pouch–anal anastomosis for ulcerative colitis

OBJECTIVES:Chronic inflammation in the ileal pouch is the most significant late complication after ileal pouch–anal anastomosis (IPAA). It leads to changes in mucosal morphology, with consequent decreased vitamin B12, bile acid and cholesterol absorption documented. The aims of this study were to evaluate long term metabolic consequences at least 5 yr after IPAA and the influence of pouchitis on pouch histology and on bile acid, lipid, and vitamin B12, A, E, and D metabolism.METHODS:A total of 104 patients with a J-pouch who were operated on between 1985 and 1994, as well as 21 ulcerative colitis patients with a conventional ileostomy were enrolled for the study. Routine blood tests, vitamin status, vitamin B12 levels, and bile acid absorption were determined, as well as endoscopy with biopsies. The pouchitis disease activity index (PDAI) was calculated. On the basis of histology, IPAA patients were divided into three subgroups: 1) those with no villous atrophy, 2) those with partial villous atrophy, and 3) those with subtotal or total villous atrophy.RESULTS:Incidence of pouchitis was 42.3%, and was strongly associated with villous atrophy. In IPAA patients with subtotal or total villous atrophy (32.7%), serum levels of albumin, calcium, total cholesterol, triglycerides, and vitamin E were significantly reduced (p < 0.05). The lowest bile acid and vitamin B12 absorption rates were seen in patients with inflammation in the proximal limb. Vitamin D deficiency was seen in 10.6%, and vitamin A and B12 deficiency in approximately 5% of IPAA patients.CONCLUSIONS:Metabolic consequences after IPAA are associated with pouchitis, grade of villous atrophy, and extent of inflammation in the remaining ileum. Patients with active chronic inflammation need long term follow-up.

Risk of Osteopenia after Proctocolectomy and Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Background: The aim of our study was to evaluate the influence of pouchitis and villous atrophy on bone mineral density and metabolism at least 5 years after ileal pouch-anal anastomosis for ulcerative colitis (UC). Methods: Eighty-eight subjects with a J-pouch operated on between 1985 and 1994, and 20 ulcerative colitis subjects with a conventional ileostomy were enrolled. Endoscopy was performed and spine and femoral neck bone mineral densities measured. Bone metabolism was assessed by measurement of serum levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D 3, calcium, alkaline phosphatase and urinary N-telopeptide cross-linked of type I collagen (NTX). Results: In the lumbar spine, 37% of the J-pouch subjects with subtotal to total villous atrophy had osteopenia (Z score <-1), whereas none of the subjects with normal villous structure had reduced bone densities in the spine or femoral neck. The highest prevalence of osteopenia (66.7%) and the lowest spine (mean-0.89 ± 0.36; P = 0.006) and femoral neck (mean-0.63 ± 0.29; P = 0.07) Z scores were found among the patients ( n = 12) with inflammation in the proximal limb of the pouch. No biochemical parameters were found to predict osteopenia and in stepwise regression analysis, the only independent risk factors for osteopenia were low body mass index and villous atrophy. Conclusions: Patients with a J-pouch showing high inflammatory activity and villous atrophy in the pouch need long-term follow-up and should be ensured adequate intake of calcium and vitamin D.

Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission.

Background:Few data are available on the disease course in patients with inflammatory bowel disease (IBD) in deep remission after discontinuing tumor necrosis factor &agr; (TNF&agr;)–blocking therapy. In this prospective multicenter study, we evaluated the relapse rate, predictive factors, and the response to retreatment after discontinuation of TNF&agr;-blocking therapy in patients with IBD in deep remission. Methods:We recruited 52 patients (17 Crohns disease, 30 ulcerative colitis, and 5 IBD unclassified) in clinical, endoscopic, and fecal calprotectin-based (<100 &mgr;g/g) remission after at least 1 year of TNF&agr;-blocking therapy. Clinical and endoscopic remission and relapse were defined according to validated indices. After discontinuation of therapy, the patients were followed up with endoscopic assessment at 4 and 12 months. In the event of a clinical relapse with endoscopically active disease or minor clinical symptoms but severe endoscopic relapse, TNF&agr;-blocking therapy was restarted. Results:After a median follow-up time of 13 (range, 12–15) months, 17/51 (33%) patients relapsed (5/17 Crohns disease, 12/34 ulcerative colitis/IBD unclassified, 1 patient lost to follow-up at 6 mo). Ten experienced clinical and endoscopic relapse, 5 clinical relapse with mild endoscopic activity, and 2 severe endoscopic relapse. No specific predictive factors were associated with the relapse. Retreatment was effective in 94% of patients. Conclusions:After cessation of TNF&agr;-blocking therapy in patients with IBD in deep remission, up to 67% remained in clinical remission during the 12-month follow-up. Importantly, 85% of these patients sustained endoscopic remission. The response to restart of TNF&agr; antagonists was effective and well tolerated.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab – a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO)*

Abstract Objectives: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn’s disease (CD) and ulcerative colitis (UC) patients. Methods: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. Results: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=−5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =−0.5, p = .003) at month 6. Conclusions: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Interactions between diet, intestinal microflora and mucosal morphology in patients with ileal pouch-anal anastomosis

Interactions Between Diet, Intestinal Microflora And Mucosal Morphology In Patients With Ileal Pouch-Anal Anastomosis Juha Kuisma, Dept of Gastroenterology, Helsinki Univ Cent, Helsinki Finland; Silja Mentula, National Public Health Institute, Helsinki Finland; Pekka Luukkonen, Dept of Surg, Helsinki Univ Cent Hosp, Helsinki Finland; Arvi Kahri, Dept of Pathology, Univ of Helsinki, Helsinki Finland; Heikki Jarvinen, Dept of Surg, Helsinki Univ Cent Hosp, Helsinki Finland; Hannele Jousimies-Somer, National Public Health Institute, Helsinki Finland; Martti Farkkila, Dept of Gastroenterology, Helsinki Univ Cent, Helsinki Finland