Real-life treatment persistence and treatment outcomes of Finnish patients with inflammatory bowel disease receiving vedolizumab as first-line biological treatment.

Purpose: To analyze treatment persistence and treatment outcomes of vedolizumab as first-line biological treatment in Crohn's disease (CD) and ulcerative colitis (UC) patients in a Finnish real-world setting. Methods: Observational, retrospective, multi-center chart review study that included adult CD and UC patients initiating vedolizumab as first-line biological treatment between 2014 and 2020. Results: The cohort consisted of 54 CD and 69 UC patients. At month 12, treatment persistence was 84.9 % in CD and 64.7 % in UC. Most vedolizumab discontinuations (CD, n = 11; UC, n = 26) were due to inefficacy. Discontinuations due to adverse events were rare (n < 5). Efficacy improvements were observed in treatment persistent patients at 12 months vs. baseline in the Harvey-Bradshaw Index (CD, 1.8 vs. 3.9, p = 0.001), Partial Mayo Score (UC, 1.0 vs. 4.9, p < 0.001), Physician's Global Assessment (CD, 0.9 vs. 1.8, p < 0.001; UC, 0.4 vs. 2.1, p < 0.001), along with positive endoscopic and biochemical outcomes. Clinical remission was 90.9 % vs. 63.0 % for CD, and 81.6 % vs. 12.3 % for UC, while corticosteroid use was 15.9 % vs. 53.7 % for CD, and 14.6 % vs. 92.8 % for UC at 12 months and baseline, respectively. Conclusion: Vedolizumab was associated with improvements in efficacy, endoscopic activity, biochemical parameters, and decreased corticosteroid burden when used as a first-line biological treatment.

Increasing Incidence of Inflammatory Bowel Disease, with Greatest Change Among the Elderly: A Nationwide Study in Finland, 2000-2020.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease [IBD] is stabilising in many Western countries. Some still show increasing incidence. Our objective was to determine the latest trends in IBD incidence and prevalence in Finland and to compare these among different age groups and between different geographical areas. METHODS: We used the nationwide registry of the Social Insurance Institute of Finland to identify new IBD cases during the period 2000-2020. Crude, age-specific, and age-standardised incidence rates were calculated. Prevalence was estimated using valid reimbursements from the same database in 2000-2020. RESULTS: We identified 42 498 new IBD cases. The crude annual incidence increased in ulcerative colitis [UC] from 20 to 35 (incidence date ratio [IRR] 1.03, 95% confidence interval [CI] 1.02-1.03), in Crohn's disease [CD] from 8 to 13 [IRR 1.02, CI 1.02-1.03] and in IBD overall from 28 to 48 per 100 000 person-years [IRR 1.02, CI 1.02-1.03]. Men had higher incidence than women in UC, but in CD the incidences were equal. The incidence of IBD increased in all age groups except for small children. The increase in both UC and CD was most marked among the elderly aged over 70. A north-south gradient was discernible. The crude prevalence of IBD increased from 376 to 972 per 100 000 (prevalence rate ratio [PRR] 1.05, CI 1.05-1.05). CONCLUSIONS: The incidence of IBD, UC, and CD is increasing in Finland. The increase is most notable in the elderly. Current prevalence of IBD is 1%.

Long-term outcomes of patients with acute severe ulcerative colitis treated with cyclosporine rescue therapy.

BACKGROUND AND AIMS: The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here. METHODS: All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records. RESULTS: A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC. CONCLUSION: In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy.

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study.

BACKGROUND AND AIMS: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. MATERIALS AND METHODS: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. RESULTS: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). CONCLUSION: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids.

BACKGROUND AND AIMS: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here. MATERIALS AND METHODS: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed. RESULTS: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1-10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed. CONCLUSION: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare.

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort.

OBJECTIVE: Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab. METHODS: The study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records. RESULTS: The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P < 0.001) and faecal calprotectin from 776 to 305 µg/g (P < 0.001). CONCLUSIONS: Ustekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.

Clozapine-Related Diarrhea and Colitis: Report of 4 Cases.

BACKGROUND: During clozapine treatment, diarrhea is a rare but clinically relevant adverse effect. Cases of microscopic colitis and eosinophilic colitis have been previously reported. PROCEDURES: We present 4 patients who developed severe diarrhea in early weeks of clozapine therapy. FINDINGS: Two patients had significant peripheral eosinophilia 1 week after diarrhea symptoms. One of these patients also had Charcot-Leyden crystals in stool afterward, confirming the presence of eosinophils in the gut lumen. One of our patients had a confirmed microscopic colitis and later also neutropenia, which required treatment. CONCLUSIONS: Charcot-Leyden crystals in stool may be associated with concurrent diarrhea and eosinophilia during clozapine treatment, which is a previously unreported finding. Occurrence of blood dyscrasias with diarrhea symptoms during clozapine treatment needs further investigation to understand the possible shared mechanisms.

Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland.

Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC).Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study.Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types.Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2-8.1).Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed.

Characterization of inflammatory bowel disease management by vedolizumab and concomitant treatments in real-life clinical practice.

Limited data is available on vedolizumab combination therapies in real-world clinical practice. Here, we evaluated the concomitant corticosteroid, immunosuppressive, and 5-aminosalicylic acid utilization of inflammatory bowel disease (IBD) patients treated with vedolizumab in a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centres with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) who had at least one vedolizumab infusion since it's availability in Finland were included in the study. Data were collected from medical charts at baseline (vedolizumab treatment initiation), week 14, and month 6. The majority of patients who used corticosteroids at the baseline and persisted on vedolizumab treatment for 6 months were taken off corticosteroid treatment by the 6-month time point (CD, 54.5%; UC, 69.8%). Modest corticosteroid dose reductions were observed among treatment persistent CD patients from the baseline until month 6. Corticosteroid users had less vedolizumab discontinuations due to primary ineffectiveness and more discontinuations due to adverse events than patients not using corticosteroids. Vedolizumab may have a corticosteroid sparing effect in real-world clinical practice. Concomitant corticosteroid use may lead to a lower rate of vedolizumab discontinuation due to primary ineffectiveness, but a higher discontinuation rate due to adverse events.

The impacts of an inflammatory bowel disease nurse specialist on the quality of care and costs in Finland.

INTRODUCTION: A specialized inflammatory bowel disease (IBD) nurse is considered a valuable and cost-effective member of a multidisciplinary team, not all clinics responsible for IBD care employ such nurses. We evaluated IBD nurse resources, quality of care and cost effects on IBD patients care in a nationwide study in Finland. METHODS: A healthcare professional electronic survey was conducted in order to assess the impact of an IBD nurse on the quality of care. To study the cost effects, we obtained nationwide comprehensive data covering years between 2008 and 2016 from major administrative healthcare districts of Finland. Patients with a diagnosis of IBD (ICD-code K50 or K51) were identified from the data and their personal contacts and hospitalization were analyzed. The results were compared between healthcare districts with an IBD nurse and healthcare districts without an IBD nurse. RESULTS: Forty-nine physicians and 88 nurses responded to the survey. Of the physicians, 92% reported that an established IBD nurse had released physician's resources. The most important IBD nurse contributions listed were patient support and follow-up (79-81% of the respondents). Healthcare district, which had an established IBD nurse, produced more patient contacts. A larger proportion of the contacts was managed by the IBD nurse. Clinics with an IBD nurse reported less patient hospitalization (4-9% vs 11-19%, p < .001). Estimated annual cost savings while employing an IBD nurse may be significant. CONCLUSION: The introduction of an IBD nurse led to better quality of care and potentially significant cost savings by reducing hospitalization rates and reallocating physician's time resources.

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

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.

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents.

BACKGROUND: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers. METHODS: The first follow-up data of 51 IBD patients (17 Crohn's disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months. RESULTS: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients. CONCLUSION: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31-41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.

[What have biological drugs changed in inflammatory rheumatic, skin and bowel diseases?]. / Mitä biologiset lääkkeet ovat muuttaneet tulehduksellisten reuma-, iho- ja suolistosairauksien hoidossa?

Biological drugs are the most rapidly growing group of medicinal agents. In addition to hormone and vaccine products, the significance of drugs produced using genetic engineering has increased in numerous indications, especially in oncology. Furthermore, they have significantly contributed to the treatment of inflammatory musculoskeletal as well as cutaneous and intestinal diseases. Their use is limited by parenteral administration, immunogenicity, uncertainty about possible severe adverse effects and especially the high price of the drugs. The cessation of patent protection of the original brand pharmaceuticals, and marketing of biosimilar drugs are expected to lower the prices of the original biological, as well.

Cerebrovascular events in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents.

BACKGROUND AND AIMS: Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients. METHODS: This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project. A call to all ECCO members was made to report on IBD patients afflicted with CVA during treatment with anti-TNF alpha agents. Clinical data were recorded in a standardised case report form and analysed for event association with anti-TNF alpha treatment. RESULTS: A total of 19 patients were identified from 16 centres: 14 had Crohn's disease, four ulcerative colitis and one IBD colitis unclassified [median age at diagnosis: 38.0 years, range: 18.6-62.5]. Patients received anti-TNF alpha for a median duration of 11.8 months [range: 0-62] at CVA onset; seven had previously been treated with at least one other anti-TNF alpha agent. Complete neurological recovery was observed in 16 patients. Anti-TNF alpha was discontinued in 16/19 patients. However, recurrent CVA or neurological deterioration was not observed in any of the 11 patients who received anti-TNF alpha after CVA [eight resumed after temporary cessation, three continued without interruption] for a median follow-up of 39.8 months [range: 5.6-98.2]. CONCLUSION: These preliminary findings do not unequivocally indicate a causal role of anti-TNF alpha in CVA complicating IBD. Resuming or continuing anti-TNF alpha in IBD patients with CVA may be feasible and safe in selected cases, but careful weighing of IBD activity versus neurological status is prudent.

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 Crohn's 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.

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 α (TNFα)-blocking therapy. In this prospective multicenter study, we evaluated the relapse rate, predictive factors, and the response to retreatment after discontinuation of TNFα-blocking therapy in patients with IBD in deep remission. METHODS: We recruited 52 patients (17 Crohn's disease, 30 ulcerative colitis, and 5 IBD unclassified) in clinical, endoscopic, and fecal calprotectin-based (<100 µg/g) remission after at least 1 year of TNFα-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, TNFα-blocking therapy was restarted. RESULTS: After a median follow-up time of 13 (range, 12-15) months, 17/51 (33%) patients relapsed (5/17 Crohn's 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 TNFα-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 TNFα antagonists was effective and well tolerated.

Mortality and causes of death in patients with inflammatory bowel disease: a nationwide register study in Finland.

BACKGROUND AND AIM: Increased mortality has been reported in Crohn's disease (CD) but mostly not in ulcerative colitis (UC). We evaluated the overall and cause-specific mortality in a nationwide cohort of patients with inflammatory bowel disease (IBD) in Finland. METHODS: A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the Special Reimbursement register were diagnosed 1987-1993 and 2000-2007 and followed up to the end of 2010 by collating these figures with the national computerized Cause-of-Death Register of Statistics Finland. In each cause-of-death category, the number of deaths reported was compared to that expected in general population, and expressed as a standardized mortality ratio (SMR). RESULTS: Overall mortality was increased among patients with CD (SMR 1.33, 95% confidence interval 1.21-1.46) and UC (1.10, 1.05-1.15). SMR was significantly increased for gastrointestinal causes in CD (6.53, 4.91-8.52) and UC (2.81, 2.32-3.34). Patients with UC were found also to have increased SMR from pulmonary (1.24, 1.02-1.46) and cardiovascular disease (1.14, 1.06-1.22) and cancers of the colon (1.90, 1.38-2.55), rectum (1.79, 1.14-2.69) and biliary tract (5.65, 3.54-8.54), whereas SMR from alcohol-related deaths was decreased (0.54, 0.39-0.71). Patients with CD had a significantly increased SMR for pulmonary diseases (2.01, 1.39-2.80), infections (4.27, 2.13-7.63) and cancers of the biliary tract (4.51, 1.23-11.5) and lymphoid and hematopoietic tissue (2.95, 1.85-4.45). CONCLUSIONS: In this Finnish nationwide study increased overall mortality in both CD and UC was observed. The excess mortality of 14% in IBD is mainly due to deaths related to inflammation in the gut.

Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case-control observational study based on registry data.

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR = 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.

Malignancies in patients with inflammatory bowel disease: a nationwide register study in Finland.

OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients.

High and increasing prevalence of inflammatory bowel disease in Finland with a clear North-South difference.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) prevalence has increased and a North-South gradient has been reported. We estimated the nationwide prevalence of IBD, ulcerative colitis (UC) and Crohn's disease (CD) in 1993, and prevalence of IBD in 2008, and assessed the geographical distribution of IBD in Finland. In addition, we investigated the vitamin D levels in a study population from a large, nationally representative health examination survey, the Health 2000 Survey. METHODS: The register study for prevalences included all patients who had special reimbursement of medications for IBD in the years 1993 (n=10,958) and 2008 (31,703). The study for D-vitamin measurement consisted of 6134 persons who had participated in the Health 2000 Survey. RESULTS: The nationwide point prevalence of IBD in 1993 was 216 per 100,000 inhabitants, and 595 in 2008. In 1993, the prevalence of UC (177) was fourfold higher than the prevalence of CD (38). The prevalence of IBD and UC in Finland increased from South to North. For CD, no geographical variation could be demonstrated. In the Health 2000 survey, vitamin D levels were lower in Northern than in Southern Finland. CONCLUSIONS: Finland belongs to high prevalence area of IBD and this prevalence has increased nearly threefold during the past 15 years. A clear North-South gradient has been shown for IBD and UC, but not for CD. Slightly lower vitamin D levels in Northern Finland may be associated with the observed higher prevalence of IBD there.