Browsing by Subject "ULCERATIVE-COLITIS"

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  • Strobbe, Floortje; Benard, Melanie; Rossen, Noortje G.; de Vos, Willem M.; Kumar, Nitin; Lawley, Trevor D.; Zoetendal, Erwin G.; Hugenholtz, Floor; Ponsioen, Cyriel Y. (2021)
    We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.
  • Huoponen, Saara; Blom, Marja (2015)
    Background Biologics are used for the treatment of inflammatory bowel diseases, Crohn's disease and ulcerative colitis refractory to conventional treatment. In order to allocate healthcare spending efficiently, costly biologics for inflammatory bowel diseases are an important target for cost-effectiveness analyses. The aim of this study was to systemically review all published literature on the cost-effectiveness of biologics for inflammatory bowel diseases and to evaluate the methodological quality of cost-effectiveness analyses. Methods A literature search was performed using Medline (Ovid), Cochrane Library, and SCOPUS. All cost-utility analyses comparing biologics with conventional medical treatment, another biologic treatment, placebo, or surgery for the treatment of inflammatory bowel diseases in adults were included in this review. All costs were converted to the 2014 euro. The methodological quality of the included studies was assessed by Drummond's, Philips', and the Consolidated Health Economic Evaluation Reporting Standards checklist. Results Altogether, 25 studies were included in the review. Among the patients refractory to conventional medical treatment, the incremental cost-effectiveness ratio ranged from dominance to 549,335 (sic)/Quality-Adjusted Life Year compared to the incremental cost-effectiveness ratio associated with conventional medical treatment. When comparing biologics with another biologic treatment, the incremental cost-effectiveness ratio ranged from dominance to 24,012,483 (sic)/Quality-Adjusted Life Year. A study including both direct and indirect costs produced more favorable incremental cost-effectiveness ratios than those produced by studies including only direct costs. Conclusions With a threshold of 35,000 (sic)/Quality-Adjusted Life Year, biologics seem to be cost-effective for the induction treatment of active and severe inflammatory bowel disease. Between biologics, the cost-effectiveness remains unclear.
  • Malinen, Erja; Krogius-Kurikka, Lotta Kaisa; Lyra, Anna; Nikkila, Janne; Jaaskelainen, Anne; Rinttila, Teemu; Vilpponen-Salmela, Terttu; von Wright, Atte Johannes; Palva, Airi (2010)
  • Kolehmainen, Sara; Ylisaukko-Oja, Tero; Jokelainen, Jari; Koivusalo, Mirkka; Jokiranta, T. Sakari; Sipponen, Taina (2021)
    Objectives We set out to determine the reasons for serum vedolizumab (VDZ) trough concentration (TC) measurements in inflammatory bowel disease (IBD) patients and to evaluate treatment modifications after therapeutic drug measurement (TDM). We also evaluated the effect of increased dosing on patients' response to VDZ therapy. Methods We performed a retrospective cohort study of IBD patients who received VDZ therapy at Helsinki University Hospital and whose VDZ levels were measured between June 2014 and December 2018. Results Altogether, 90 patients (32 Crohn's disease and 58 ulcerative colitis) and 141 VDZ TC measurements were included. 24.1% of measurements took place during induction and 75.9% during the maintenance phase. During induction, 64.7% reached the target TC >20 mu g/ml. During maintenance therapy, 82.2% of VDZ TCs were within or exceeded the suggested target range of 5-15 mu g/ml. Reasons for TDM were: secondary nonresponse (44.0%), assessment of adequate VDZ TC (25.5%), primary nonresponse (12.8%), adverse events (6.4%), and other (11.3%). No treatment changes occurred after 60.3% of VDZ measurements. Increased dose frequency was used after 25.5% of VDZ measurements and 33.3% of these patients experienced improvement. Altogether, 31 (34.4%) patients discontinued the therapy due to inadequate treatment response. No anti-vedolizumab antibodies were detected. Conclusions During the maintenance of VDZ therapy, the majority of VDZ TCs were within the suggested range. Measurement of VDZ TC did not lead to any treatment changes in two-thirds of patients. Dose optimization occurred in a quarter of patients and a third of them benefited from it.
  • Nieminen, Janne K.; Niemi, Mirja; Sipponen, Taina; Salo, Harri M.; Klemetti, Paula; Färkkilä, Martti Antero; Vakkila, Jukka; Vaarala, Outi (2013)
  • Hasan, Shah; Junnikkala, Sami; Peltoniemi, Olli; Paulin, Lars; Lyyski, Annina; Vuorenmaa, Juhani; Oliviero, Claudio (2018)
    Dietary supplementation with yeast derivatives (YD) contributes to the health and physiology of sows and piglets, but few studies have focused on how it influences gut health and performance of sows and piglets. The goal was therefore to examine whether YD, based on brewer's yeast hydrolysate added to pregnancy diet, would affect colostrum composition, yield (CY) and gut microbiota of sows and piglets. Sows were allocated to either a control diet (n = 19) or a control diet supplemented with 2g YD/kg (n = 18) during the pregnancy. Piglets suckling belonging to the control sows (n = 114) and supplemented sows (n = 108) were also included in the study. Gut microbiota populations of sows at farrowing and piglets at one and four weeks of age were assessed using 16S rRNA gene sequencing. Colostrum samples were examined for nutritional composition and immunoglobulin (Ig) content. All piglets were individually weighed at birth and 24 hours later in order to calculate CY, and later at four weeks to calculate average daily gain (ADG). Protein, lactose and dry matter content of colostrum did not significantly differ between the two groups, while sows fed YD had higher levels of fat in their colostrum (P<0.05). Immunoglobulin A, IgM and IgG levels in colostrum did not differ between the two groups (P>0.05). Colostrum yield was lower in the control than that in YD group (3701g vs. 4581 g; P
  • Peuhkuri, Katri; Vapaatalo, Heikki; Korpela, Riitta (2011)
  • Rossen, Noortje G.; MacDonald, John K.; de Vries, Elisabeth M.; D'Haens, Geert R.; de Vos, Willem M.; Zoetendal, Erwin G.; Ponsioen, Cyriel Y. (2015)
    AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. RESULTS: We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome.
  • The International PSC Study Group; The UK PSC Consortium; Alberts, Rudi; de Vries, Elisabeth M. G.; Goode, Elizabeth C.; Jiang, Xiaojun; Sampaziotis, Fotis; Rombouts, Krista; Böttcher, Katrin; Folseraas, Trine; Weismüller, Tobias J.; Mason, Andrew L.; Wang, Weiwei; Alexander, Graeme; Alvaro, Domenico; Bergquist, Annika; Björkström, Niklas K.; Beuers, Ulrich; Björnsson, Einar; Boberg, Kirsten Muri; Bowlus, Christopher L.; Bragazzi, Maria C.; Carbone, Marco; Chazouilleres, Olivier; Cheung, Angela; Dalekos, Georgios; Eaton, John; Eksteen, Bertus; Ellinghaus, David; Färkkilä, Martti Antero; Festen, Eleonora A. M.; Floreani, Annarosa; Franceschet, Irene; Gotthardt, Daniel Nils; Hirschfield, Gideon M.; van Hoek, Bart; Holm, Kristian; Hohenester, Simon; Hov, Johannes Roksund; Imhann, Floris; Invernizzi, Pietro; Juran, Brian D.; Lenzen, Henrike; Lieb, Wolfgang; Liu, Jimmy Z.; Marschall, Hanns-Ulrich; Marzioni, Marco; Melum, Espen; Milkiewicz, Piotr; Müller, Tobias; Pares, Albert; Rupp, Christian; Rust, Christian; Sandford, Richard N.; Schramm, Christoph; Schreiber, Stefan; Schrumpf, Erik; Silverberg, Mark S.; Srivastava, Brijesh; Sterneck, Martina; Teufel, Andreas; Vallier, Ludovic; Verheij, Joanne; Vila, Arnau Vich; de Vries, Boudewijn; Zachou, Kalliopi; Chapman, Roger W.; Manns, Michael P.; Pinzani, Massimo; Rushbrook, Simon M.; Lazaridis, Konstantinos N.; Franke, Andre; Anderson, Carl A.; Karlsen, Tom H.; Ponsioen, Cyriel Y.; Weersma, Rinse K. (2018)
    Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
  • Sidoroff, Marianne; Karikoski, Riitta; Raivio, Taneli; Savilahti, Erkki; Kolho, Kaija-Leena (2010)
  • Hanifeh, Mohsen; Rajamäki, Minna Marjaana; Syrjä, Pernilla; Mäkitalo, Laura; Kilpinen, Susanne; Spillmann, Thomas (2018)
    Background: Matrix metalloproteinases (MMPs) 2 and 9 are zinc-and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro-and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs. Results: In dogs with CE, the number of samples positive for mucosal pro-and active MMP-2 was significantly higher in the duodenum (P <0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P <0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples (P = 0.023). There was no significant association of pro-and active MMP-2 and -9 levels with the clinical outcome or hypoalbuminemia. Conclusions: This study is the first to demonstrate upregulation of mucosal pro-and active MMP-2 and pro-MMP-9 in the intestine of dogs with CE compared to healthy dogs. The results provide supporting evidence for the possible involvement of MMP-2 and -9 in the pathogenesis of canine CE.
  • Tenca, Andrea; Jaakkola, Tytti; Färkkilä, Martti; Arola, Johanna; Kolho, Kaija-Leena (2019)
    Introduction and aim: The aim of this study was to investigate the outcome of a paediatric onset of inflammatory bowel disease (IBD) in a cohort of subjects with primary sclerosing cholangitis (PSC) and in a matched-age population-based control group without PSC. Methods: We identified 28 IBD-PSC cases (median age at IBD diagnosis 12.5 years, 25-75th: 10-16 years) and selected three IBD controls for each case matched for age and year of IBD diagnosis. All data regarding the gastrointestinal tract and liver were collected at diagnosis and at last follow-up (median 15 years). Results: At diagnosis the prevalence of pancolitis was similar between the groups (78% and 79%, respectively p = -.30), but histologic inflammation was milder in IBD-PSC (61% vs 30%, p = .06). At last follow-up (median age 29 years) pancolitis was less frequent (6% and 33%, respectively p = .04) and the remission higher (76% and 47%, respectively p = .08) in IBD-PSC patients than in IBD patients. Panproctolectomy (32% in IBD-PSC and 34% in IBD, p = 1.0) and the rate of pouchitis (62% and 70%, respectively p = .8) were similar. Conclusions: The outcome of paediatric onset IBD in patients with PSC in adulthood seems to be comparable to those with IBD only.
  • Hamalainen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena (2011)
  • Int IBD Genetics Consortium; NIDDK IBD Genetics Consortium; T2D-Genes Consortium; Rivas, Manuel A.; Koskela, Jukka; Pirinen, Matti; Kurki, Mitja; Saavalainen, Paivi; Farkkila, Martti; Kontula, Kimmo; Palotie, Aarno; Daly, Mark J. (2018)
    As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at, also available in gnomAD at We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at, including those that account for 10 +/- 100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p. Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to fourfold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p <0.005), including several novel contributing alleles, show evidence of association to CD. Independently, we find that genomewide common variant risk defined by GWAS shows a strong difference between AJ and non-AJ European control population samples (0.97 s.d. higher, p
  • Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; de Vos, Willem M. (2017)
    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss key concepts of the human intestinal microbiome landscape, i.e. the compositional and functional 'core', the presence of community types and the existence of alternative stable states. Genomic investigation of core taxa revealed functional redundancy, which is expected to stabilize the ecosystem, as well as taxa with specialized functions that have the potential to shape the microbiome landscape. The contrast between Prevotella-and Bacteroides-dominated systems has been well described. However, less known is the effect of not so abundant bacteria, for example, Dialister spp. that have been proposed to exhibit distinct bistable dynamics. Studies employing time-series analysis have highlighted the dynamical variation in the microbiome landscape with and without the effect of defined perturbations, such as the use of antibiotics or dietary changes. We incorporate ecosystem-level observations of the human intestinal microbiota and its keystone species to suggest avenues for designing microbiome modulation strategies to improve host health.
  • Puolanne, Anna-Maija; Kolho, Kaija-Leena; Alfthan, Henrik; Färkkilä, Martti (2019)
    Objectives: The aim of this prospective study was to evaluate the home monitoring with a rapid fecal calprotectin test combined with a symptom questionnaire in patients with colonic IBD in real-life setting. Methods: We randomized 180 patients with colonic IBD in a study or a control group. The home monitoring patients performed the fecal calprotectin test and filled in a symptom questionnaire every second month and in cases with increasing symptoms. The control patients filled in the symptom questionnaire at baseline and at 6 and 12 months as well as for the appointment at the outpatient clinic. The study duration was 12 months. Results: The patient adherence to the self-monitoring program was low. Patients with a higher disease burden were more adherent than patients with better health-related quality of life, but otherwise, there were no significant factors predicting the adherence. The home monitoring patients had fewer contacts with the outpatient clinic, but otherwise, the disease course between the home monitoring and the control group were similar. Conclusions: The self-monitoring of IBD activity with a combination of a rapid fecal calprotectin home test and a symptom questionnaire provides an option for individualized care for IBD patients. However, adherence to the self-monitoring program remains a challenge.
  • Heikkila, Katriina; Madsen, Ida E. H.; Nyberg, Solja T.; Fransson, Eleonor I.; Ahola, Kirsi; Alfredsson, Lars; Bjorner, Jakob B.; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Ferrie, Jane E.; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Nielsen, Martin L.; Nordin, Maria; Pejtersen, Jan H.; Pentti, Jaana; Rugulies, Reiner; Oksanen, Tuula; Shipley, Martin J.; Suominen, Sakari B.; Theorell, Tores; Vaananen, Ari; Vahtera, Jussi; Virtanen, Marianna; Westerlund, Hugo; Westerholm, Peter J. M.; Batty, G. David; Singh-Manoux, Archana; Kivimaki, Mika; IPD-Work Consortium (2014)
  • Molander, Pauliina; Farkkila, Martti; Kemppainen, Helena; Blomster, Timo; Jussila, Airi; Mustonen, Harri; Sipponen, Taina (2017)
    Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNF alpha-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNF alpha-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 TNF alpha-blocking therapy, the predicting factors of a relapse and the response to restarting TNF alpha-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 TNF alpha-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 TNF alpha-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 TNF alpha-blockers seems to be effective and well tolerated.
  • Voutilainen, Markku; Hutri-Kähönen, Nina; Tossavainen, Päivi; Sipponen, Taina; Pitkänen, Niina; Laitinen, Tomi; Jokinen, Eero; Rönnemaa, Tapani; Viikari, Jorma S. A.; Raitakari, Olli T.; Juonala, Markus (2018)
    Background and aims: Several genetic and environmental risk factors have been linked to chronic inflammatory bowel disease (IBD). The incidence of IBD has significantly increased in developed countries during last decades. The aim of the present study was to examine childhood risk factors for subsequent IBD diagnosis in a longitudinal cohort study of children and adolescents. Methods: A Finnish study population consisting of 3551 children and adolescents originally evaluated as part of the Cardiovascular Risk in Young Finns study in 1980. At baseline, participant BMI, insulin, lipid, C-reactive protein and blood pressure levels, socioeconomic position, dietary habits, and physical activity, were evaluated. In addition, information was gathered on rural residency, severe infections, breast feeding, parental smoking and birth weight. Subsequent IBD diagnosis status was evaluated based on nationwide registries on hospitalisations and drug imbursement decisions. Results: Altogether, 49 participants (1.4%) had IBD diagnosed during the 34 years of register follow-up, of which 31 had ulcerative colitis, 12 Crohn's disease and 6 undetermined colitis. In univariate analyses, significant correlations were observed between childhood HDL-cholesterol (risk ratio (95% CI) for 1-SD change (0.58 (0.42-0.79)) and CRP concentrations (1.20 (1.01-1.43)) with IBD. The inverse association between HDL-cholesterol and IBD remained significant (0.57 (0.39-0.82)) in a multivariable model including data on age, sex and CRP. In addition, a weighted genetic z-score of 71 single nucleotide polymorphisms associated with elevated HDL-cholesterol levels was significantly lower in IBD patients, p = 0.01). Conclusion: Low childhood HDL-cholesterol levels are associated with subsequent IBD diagnosis. In addition, a genetic risk score associated with low HDL-cholesterol levels predict later IBD suggesting that HDL-cholesterol metabolism might have a role in the pathogenesis of IBD. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.