Tulehduksellisten suolistosairauksien hoito - mitä uutta?

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Noninvasive monitoring of activity in Crohn's disease

Background: The fecal neutrophil-derived proteins calprotectin and lactoferrin have proven useful surrogate markers of intestinal inflammation. The aim of this study was to compare fecal calprotectin and lactoferrin concentrations to clinically, endoscopically, and histologically assessed Crohn’s disease (CD) activity, and to explore the suitability of these proteins as surrogate markers of mucosal healing during anti-TNFα therapy. Furthermore, we studied changes in the number and expression of effector and regulatory T cells in bowel biopsy specimens during anti-TNFα therapy. Patients and methods: Adult CD patients referred for ileocolonoscopy (n=106 for 77 patients) for various reasons were recruited (Study I). Clinical disease activity was assessed with the Crohn’s disease activity index (CDAI) and endoscopic activity with both the Crohn’s disease index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD). Stool samples for measurements of calprotectin and lactoferrin, and blood samples for CRP were collected. For Study II, biopsy specimens were obtained from the ileum and the colon for histologic activity scoring. In prospective Study III, after baseline ileocolonoscopy, 15 patients received induction with anti-TNFα blocking agents and endoscopic, histologic, and fecal-marker responses to therapy were evaluated at 12 weeks. For detecting changes in the number and expression of effector and regulatory T cells, biopsy specimens were taken from the most severely diseased lesions in the ileum and the colon (Study IV). Results: Endoscopic scores correlated significantly with fecal calprotectin and lactoferrin (p5 mg/l were 48%, 91%, 91%, and 48%. Fecal markers were significantly higher in active colonic (both p<0.001) or ileocolonic (calprotectin p=0.028, lactoferrin p=0.004) than in ileal disease. In ileocolonic or colonic disease, colon histology score correlated significantly with fecal calprotectin (r=0.563) and lactoferrin (r=0.543). In patients receiving anti-TNFα therapy, median fecal calprotectin decreased from 1173 μg/g (range 88-15326) to 130 μg/g (13-1419) and lactoferrin from 105.0 μg/g (4.2-1258.9) to 2.7 μg/g (0.0-228.5), both p=0.001. The relation of ileal IL-17+ cells to CD4+ cells decreased significantly during anti-TNF treatment (p=0.047). The relation of IL-17+ cells to Foxp3+ cells was higher in the patients’ baseline specimens than in their post-treatment specimens (p=0.038). Conclusions: For evaluation of CD activity, based on endoscopic findings, more sensitive surrogate markers than CDAI and CRP were fecal calprotectin and lactoferrin. Fecal calprotectin and lactoferrin were significantly higher in endoscopically active disease than in endoscopic remission. In both ileocolonic and colonic disease, fecal markers correlated closely with histologic disease activity. In CD, these neutrophil-derived proteins thus seem to be useful surrogate markers of endoscopic activity. During anti-TNFα therapy, fecal calprotectin and lactoferrin decreased significantly. The anti-TNFα treatment was also reflected in a decreased IL-17/Foxp3 cell ratio, which may indicate improved balance between effector and regulatory T cells with treatment.Crohnin tauti on krooninen, tulehduksellinen suolistosairaus, jolle on tyypillistä jaksottainen ja usein suolen seinämän syvempiin osiin ulottuva tulehdus. Tavanomaiset, verestä määritettävät tulehduksen merkkiaineet CRP ja lasko eivät ole riittävän herkkiä suolen limakalvon tulehduksen arvioinnissa. Ulosteesta mitattavat, tulehduksen yhteydessä valkosoluista vapautuvat merkkiaineet kalprotektiini ja laktoferriini ovat osoittautuneet luotettaviksi suolen tulehduksellisten ja ei-tulehduksellisen tilojen erotusdiagnostiikassa. Näiden ulosteen merkkiaineiden käyttökelpoisuudesta Crohnin taudin aktiivisuuden monitoroinnissa on niukasti tietoa. Tämän väitöskirjatutkimuksen tavoitteena oli selvittää, miten ulosteen kalprotektiini ja laktoferriini korreloivat Crohnin taudin kliiniseen, endoskooppiseen ja histologiseen aktiivisuuteen ja miten ne toimivat Crohnin taudin hoidon monitoroinnissa. Lisäksi tarkastelimme suolen limakalvon effektori- ja regulatoristen T-solujen suhteen muutoksia TNF-alfa-salpaajahoidon aikana. Tutkimuksen ensimmäisessä osatyössä havaittiin, että ulosteen merkkiaineet kalprotektiini ja laktoferriini korreloivat hyvin Crohnin taudin endoskooppiseen aktiivisuuteen. Tämä korrelaatio oli parempi kuin tähystyslöydöksen korrelaatio taudin kliiniseen aktiivisuuteen tai seerumin CRP-arvoon. Kumpikin merkkiaine oli merkitsevästi korkeampi endoskooppisesti aktiivisessa kuin ei-aktiivisessa Crohnin taudissa. Ulosteen kalprotektiini ja laktoferriini olivat selvemmin koholla niillä potilailla, joilla tähystyksessä todettiin aktiivinen paksusuolen tai paksusuolen ja ohutsuolen loppuosan Crohnin tauti kuin niillä potilailla, joilla oli ohutsuolen loppuosaan rajoittuva tauti. Toisessa osatyössä osoitettiin Crohnin taudin histologisen aktiivisuuden korreloivan hyvin ulosteen merkkiaineisiin paksusuolen sekä paksusuolen ja ohutsuolen loppuosan Crohnin taudissa. Kolmannessa osatyössä havaittiin ulosteen kalprotektiinin ja laktoferriinin laskevan TNF-alfa-salpaajahoidon aikana merkitsevästi: ulosteen kalprotektiinin mediaaniarvo laski tasolta 1173 μg/g (normaali < 100 μg/g) tasolle 130 μg/g ja ulosteen laktoferriini laski tasolta 105,0 μg/g tasolle 2,7 μg/g (normaali < 7,25 μg/g). Neljännessä osatyössä osoitettiin ohutsuolen loppuosasta otetuissa koepaloissa effektori- ja regulatoristen T-solujen solujen suhteen pienentyvän TNF-alfa-salpaajahoidon aikana kuvastaen todennäköisesti hoidon myötä parantunutta effektori- ja regulatoristen T-solujen tasapainoa. Ulosteen kalprotektiini ja laktoferriini näyttävät soveltuvan hyvin Crohnin taudin aktiivisuuden arviointiin ja ovat herkempiä aktiivisuuden mittareita kuin laajalti käytössä oleva seerumin CRP-arvo. Nämä valkosoluproteiinit ovat käyttökelpoisia Crohnin taudin hoitovasteen monitoroinnissa

Fragmented management of long-term parenteral support for adult intestinal failure in Finland

Objectives: Parenteral support (PS) is the first-line therapy for intestinal failure (IF). Optimal patient outcomes require experienced multidisciplinary teams adhering to structured protocols. As practices to provide long-term PS for adult IF patients in Finland are unknown, this cross-sectional nationwide study aimed to evaluate current management of PS for adult IF across the country.Materials and methods: An internet-based survey was emailed to all Finnish hospitals and hospital-at-home services with the potential to provide PS for adult IF. The survey included 20 items addressing the provision of long-term PS for adult IF patients (aged >= 18years). Data were analysed using descriptive statistics.Results: Overall, 52 (47%) of the 111 identified units responded. Of responding units, 38 (73%) had at some point provided long-term (>= 120days) PS for adult IF, and 23 (44%) had done so during the preceding year. Only three units currently managed >= 3 adult patients. Most (65%) of the respondents worked in a hospital and were either physicians (38%) or dietitians (39%). Only 65% of respondents reported that their unit had an assigned physician responsible for PS provision, and 28% reported that a team was responsible for long-term PS. Only 26% of respondents reported having a written protocol to guide PS management.Conclusions: Health care providers with very limited experience and a fragmented approach manage most Finnish adult IF patients. Evidence-based protocols and multidisciplinary teams are scarce. The care for adult IF patients on long-term PS needs to be improved in Finland.Peer reviewe

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Perianaalifistuloiva Crohnin tauti ja sen hoito

English summaryPeer reviewe

Longitudinal evolution of catheter-related bloodstream infections, kidney function and liver status in a nationwide adult intestinal failure cohort

Objectives The development of intestinal failure-related complications in Finnish adults is unknown. This study aimed to investigate the incidence of catheter-related bloodstream infections (CRBSI), and the longitudinal changes in biochemical liver and kidney tests in a nationwide cohort. Materials and methods The search for Finnish adults with intestinal failure (IF) utilized a survey to Finnish health-care providers (n = 111) with the potential to provide long-term parenteral support (PS) for adult IF. Our nationwide, cross-sectional cohort included all IF patients aged >= 18 years who had received PS for >= 120 d in 2017. Data regarding CRBSI and biochemical liver and kidney tests were collected from patient records at the start of PS up to the latest available measurement in 2017. Results In the nationwide cohort of 52 patients, the CRBSI incidence was 1.35/1000 catheter days. Seventy-three percent of CRBSI in a long-term catheter led to catheter replacement. During a median PS duration of 27.5 (interquartile range [IQR] 11.3-57.3) months, a statistically significant median change occurred in estimated glomerular filtration rate (eGFR; -8.5 ml/min/1.73 m(2), IQR -30-7, p = .005) and alkaline phosphatase (ALP; 26 U/l, IQR -11-95, p = .019). In a multiple regression model for eGFR at data collection, baseline eGFR and age were strong explanatory variables. Conclusions Incidence of CRBSI, but not treatment strategies, in this nationwide adult IF population correspond well to those reported from specialized centers. Decreased kidney function and abnormal liver test results are frequent findings, and even more so over time, emphasizing the importance of regular monitoring.Peer reviewe

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

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

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.Peer reviewe

Benefit of measuring vedolizumab concentrations in inflammatory bowel disease patients in a real-world setting

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.Peer reviewe