Browsing by Subject "CROHNS-DISEASE"

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  • Hetemaki, Iivo; Jarva, Hanna; Kluger, Nicolas; Baldauf, Hanna-Mari; Laakso, Sini; Bratland, Eirik; Husebye, Eystein S.; Kisand, Kai; Ranki, Annamari; Peterson, Part; Arstila, T. Petteri (2016)
    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.
  • Fedirko, Veronika; Jenab, Mazda; Meplan, Catherine; Jones, Jeb S.; Zhu, Wanzhe; Schomburg, Lutz; Siddiq, Afshan; Hybsier, Sandra; Overvad, Kim; Tjonneland, Anne; Omichessan, Hanane; Perduca, Vittorio; Boutron-Ruault, Marie-Christine; Kuehn, Tilman; Katzke, Verena; Aleksandrova, Krasimira; Trichopoulou, Antonia; Karakatsani, Anna; Kotanidou, Anastasia; Tumino, Rosario; Panico, Salvatore; Masala, Giovanna; Agnoli, Claudia; Naccarati, Alessio; Bueno-de-Mesquita, Bas; Vermeulen, Roel C. H.; Weiderpass, Elisabete; Skeie, Guri; Nost, Therese Haugdahl; Lujan-Barroso, Leila; Ramon Quiros, J.; Maria Huerta, Jose; Rodriguez-Barranco, Miguel; Barricarte, Aurelio; Gylling, Bjoern; Harlid, Sophia; Bradbury, Kathryn E.; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc; Murphy, Neil; Freisling, Heinz; Tsilidis, Kostas; Aune, Dagfinn; Riboli, Elio; Hesketh, John E.; Hughes, David J. (2019)
    Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (P-ACT = 0.10; P-ACT significance threshold was P <0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
  • Pfaller, Birgit; Yepes-Nuñez, Juan José; Agache, Ioana; Akdis, Cezmi A.; Alsalamah, Mohammad; Bavbek, Sevim; Bossios, Apostolos; Boyman, Onur; Chaker, Adam; Chan, Susan; Chatzipetrou, Alexia; du Toit, George; Jutel, Marek; Kauppi, Paula; Kolios, Antonios; Li, Carmen; Matucci, Andrea; Marson, Alanna; Bendien, Sarah; Palomares, Oscar; Rogala, Barbara; Szepfalusi, Zsolt; Untersmayr, Eva; Vultaggio, Alessandra; Eiwegger, Thomas (2021)
    Abstract Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
  • Forsgard, Richard A.; Marrachelli, Vannina G.; Korpela, Katri; Frias, Rafael; Carmen Collado, Maria; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Osterlund, Pia (2017)
    Purpose Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. Methods A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR). Results Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)(3) moieties and decreased the levels of Krebs cycle metabolites and free amino acids. Conclusions Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.
  • Castaneda, Anu E.; Tuulio-Henriksson, Annamari; Aronen, Eeva T.; Marttunen, Mauri; Kolho, Kaija-Leena (2013)
  • Koenig, J.; Siebenhaar, A.; Hoegenauer, C.; Arkkila, P.; Nieuwdorp, M.; Noren, T.; Ponsioen, C. Y.; Rosien, U.; Rossen, N. G.; Satokari, R.; Stallmach, A.; de Vos, W.; Keller, J.; Brummer, R. J. (2017)
    Background Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. Aim To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. Methods Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. Results Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. Conclusions Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
  • Cheng, Jing; Kalliomaki, Marko; Heilig, Hans G. H. J.; Palva, Airi; Lahteenoja, Hannu; de Vos, Willem M.; Salojarvi, Jarkko; Satokari, Reetta (2013)
  • Peuhkuri, Katri; Vapaatalo, Heikki; Korpela, Riitta (2011)
  • Wacklin, Pirjo; Tuimala, Jarno; Nikkila, Janne; Tims, Sebastian; Makivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Matto, Jaana (2014)
  • Aalto, Kristiina; Lahdenne, Pekka; Kolho, Kaija-Leena (2017)
    Background: Patients with juvenile idiopathic arthritis (JIA) on non-steroidal anti- inflammatory drugs (NSAIDs) may experience abdominal pain. In adults, NSAID use has been linked to an increase in fecal calprotectin (FC) levels, a surrogate marker for gut inflammation. In JIA, data on gut inflammation related to drug use is scarce. Methods: JIA patients followed up at the outpatient pediatric rheumatology clinic in Children's Hospital, Helsinki University Hospital, Helsinki, Finland were routinely assessed for FC if they complained about abdominal pain, had an elevated erythrocyte sedimentation rate (ESR) or used NSAIDs on a daily basis. The FC levels were related to the presence of abdominal pain, to ESR, and to the presence of HLA-B27. Results: Of the total group of 90 patients (median age 9.1 years; 45 JIA patients with disease modifying antirheumatic drugs (DMARDs), 25 without DMARD medication, and 20 arthralgia patients as controls), approximately 50% used NSAIDs, of whom 40% complained about abdominal pain. In patients with abdominal pain, one-third had elevated FC values (>100 mu g/g). The FC values, for the most part, declined along with the discontinuation or reduction of NSAIDs and after intensifying the DMARD medication, where after the pain disappeared. In patients with an elevated ESR, the FC values and ESR normalized in parallel. The presence of HLA-B27 was not associated with FC levels. Conclusion: In patients with JIA and abdominal pain, it may be useful to determine the FC when evaluating the need for further gastrointestinal examinations.
  • Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B.; Behrens, Sabine; Goode, Ellen L.; Bolla, Manjeet K.; Dennis, Joe; Dunning, Alison M.; Easton, Douglas F.; Wang, Qin; Benitez, Javier; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Fasching, Peter A.; Haeberle, Lothar; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guenel, Pascal; Truong, Therese; Bojesen, Stig E.; Flyger, Henrik; Nielsen, Sune F.; Nordestgaard, Borge G.; Gonzalez-Neira, Anna; Menendez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Doerk, Thilo; Bogdanova, Natalia V.; Mannermaa, Arto; Hartikainen, Jaana M.; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J.; Hallberg, Emily; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S.; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Garcia-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S.; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S.; Pharoah, Paul D. P.; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B.; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny (2016)
    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A > G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 x 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 x 10(-3) and 7.0 x 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 x 10(-3), 4.5 x 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.
  • Sidoroff, Marianne; Karikoski, Riitta; Raivio, Taneli; Savilahti, Erkki; Kolho, Kaija-Leena (2010)
  • Muszer, Magdalena; Noszczynska, Magdalena; Kasperkiewicz, Katarzyna; Skurnik, Mikael (2015)
    The microorganisms that inhabit humans are very diverse on different body sites and tracts. Each specific niche contains a unique composition of the microorganisms that are important for a balanced human physiology. Microbial cells outnumber human cells by tenfold and they function as an invisible organ that is called the microbiome. Excessive use of antibiotics and unhealthy diets pose a serious danger to the composition of the microbiome. An imbalance in the microbial community may cause pathological conditions of the digestive system such as obesity, cancer and inflammatory bowel disease; of the skin such as atopic dermatitis, psoriasis and acne and of the cardiovascular system such as atherosclerosis. An unbalanced microbiome has also been associated with neurodevelopmental disorders such as autism and multiple sclerosis. While the microbiome has a strong impact on the development of the host immune system, it is suspected that it can also be the cause of certain autoimmune diseases, including diabetes or rheumatoid arthritis. Despite the enormous progress in the field, the interactions between the human body and its microbiome still remain largely unknown. A better characterization of the interactions may allow for a deeper understanding of human disease states and help to elucidate a possible association between the composition of the microbiome and certain pathologies. This review focuses on general findings that are related to the area and provides no detailed information about the case of study. The aim is to give some initial insight on the studies of the microbiome and its connection with human health.
  • 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.
  • Laakso, Saila; Valta, Helena; Verkasalo, Matti; Toiviainen-Salo, Sanna-Maria; Viljakainen, Heli; Mäkitie, Outi (2012)
  • Mahiout, Selma; Tagliabue, Sara Giani; Nasri, Atefeh; Omoruyi, Iyekhoetin Matthew; Pettersson, Lars; Bonati, Laura; Pohjanvirta, Raimo (2018)
    The mediator of dioxin toxicity, aryl hydrocarbon receptor (AHR), has also important physiological functions. Selective AHR modulators (SAHRMs) share some effects of dioxins, except for their marked toxicity. We recently characterised toxicologically two novel SAHRMs, prodrugs IMA-08401 and IMA-07101 in rats, demonstrating that they are far less deleterious than the most toxic AHR-agonist, TCDD. Here, we analysed the in vitro toxicity and in silico AHR binding of the respective active, deacetylated metabolites, IMA-06201 (N-ethyl-N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-06504 (N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). In H4IIE rat hepatoma cells, IMA-06201 and IMA-06504 induced CYP1A1 with comparable potencies and efficacies to those of TCDD. They had little effect on cell viability as assessed by LDH leakage and MTT reduction assays, and were not mutagenic in the Ames test, but IMA-06504 elicited a maximally 2.7-fold increase in micronuclei. Molecular docking simulations showed that similar to TCDD, they occupy the central region of AHR ligand binding cavity. Hence, while showing low to negligible in vitro toxicity, these novel SAHRMs bind to the AHR qualitatively in a similar fashion to TCDD, and appear comparably powerful AHR agonists. Combined with our earlier results demonstrating that they seem considerably less toxic in vivo than TCDD, these compounds are thus highly interesting new SAHRMs.
  • Hamalainen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena (2011)
  • ESPGHAN; Jongsma, Maria M. E.; Winter, Dwight A.; Huynh, Hien Q.; Kolho, Kaija-Leena; de Ridder, Lissy (2020)
    Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients <10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age <10 years (young patients, YP) and PK data were available. Older IBD patients aged 10-18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 <10 year; 105 >= 10 years). Median age was 8.3 years (IQR 6.9-8.9) in YP compared with 14.3 years (IQR 12.8-15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (<5.4 mu g/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0-12.9) vs. OP; 5.5 mg/kg (IQR 5.0-9.3);p <0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI - 1.2 to - 1.01);p <0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP;p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged <10 years. What is Known?
  • 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.