Browsing by Subject "Infliximab"

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  • Malm, Heli (2020)
    Vain harvojen lääkkeiden turvallisuudesta raskauden aikana on riittävästi tietoa, jotta riskiä voidaan arvioida luotettavasti. Raskaana olevat eivät ole mukana kliinisissä lääketutkimuksissa, ja myyntiluvan myöntämisen jälkeen tietoa kertyy hajanaisesti. Lisäksi tiedon tulkinta on usein haastavaa.
  • Laharie, David; Bourreille, Arnaud; Branche, Julien; Allez, Matthieu; Bouhnik, Yoram; Filippi, Jerome; Zerbib, Frank; Savoye, Guillaume; Vuitton, Lucine; Moreau, Jacques; Amiot, Aurelien; Beaugerie, Laurent; Ricart, Elena; Dewit, Olivier; Lopez-Sanroman, Antonio; Fumery, Mathurin; Carbonnel, Franck; Buisson, Anthony; Coffin, Benoit; Roblin, Xavier; van Assche, Gert; Esteve, Maria; Färkkilä, Martti; Gisbert, Javier P.; Marteau, Philippe; Nahon, Stephane; de Vos, Martine; Peyrin-Biroulet, Laurent; Mary, Jean-Yves (2021)
    BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.
  • Ventin-Holmberg, Rebecka (Helsingin yliopisto, 2019)
    Inflammatory bowel disease (IBD) is a globally increasing chronic disease, for which the pathogenesis still is unclear. The most common subtypes of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). It is widely known that, in addition to the genetics, an altered immune response against the gut microbiome plays an important role in the development of the disease. For the IBD patients, to whom conventional medication is not sufficient, the TNF-α blocker infliximab, is given. However, about one third of the patients receiving infliximab treatment, do not respond to the drug, or lose response over time. Since there to this day are no reliable diagnostic markers available, the finding of such is of great importance. The goal of this study was to investigate possible markers for drug response in the gut mycobiota composition of IBD patients. The gut mycobiota composition of 72 IBD patients receiving infliximab was studied by MiSeq sequencing of fungal DNA from fecal samples, collected during one year. The sequencing data was analyzed using the mare package in R. In addition, anti-Saccharomyces cerevisiae antibody (ASCA) concentrations were measured from baseline serum samples by ELISA. Finally, calprotectin concentrations were measured from baseline and twelve weeks post infliximab serum samples by ELISA to study whether serum samples could be used instead of fecal samples for measuring calprotectin values. Results show an increase of the Candida and Spiromyces genera in the gut mycobiota of non-responding patients at baseline. At all timepoints, the Spiromyces genus was observed at a higher abundance, compared to the group of patients responding well or partially to the medication. Interestingly, the increase of Candida was seen only in Crohn’s disease patients, when looking at the composition at all timepoints. ASCA values did not differ between the response groups. The serum calprotectin values did not correlate with fecal calprotectin, and serum calprotectin can thus not be used as a marker of gut inflammation. In conclusion, the gut mycobiota can offer predictive markers for drug response prediction to infliximab in IBD patients, which can with further studies offer a clinical diagnostic tool for prediction of drug response.
  • Tarkiainen, Maarit; Tynjälä, Pirjo; Vähäsalo, Paula; Kröger, Liisa; Aalto, Kristiina; Lahdenne, Pekka (BioMed Central, 2019)
    Abstract Background Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. Methods In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time. Results In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS. Conclusions HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol. Trial registration This study was registered within the Hospital District of Helsinki and Uusimaa (http://www.hus.fi) clinical trials, number 211864 in October 2002, and later on with ClinicalTrials.gov, number NCT01015547.
  • Tarkiainen, Maarit; Tynjälä, Pirjo; Vähäsalo, Paula; Kröger, Liisa; Aalto, Kristiina; Lahdenne, Pekka (2019)
    Background Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. Methods In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time. Results In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS. Conclusions HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol.
  • Hämäläinen, Moona (Helsingin yliopisto, 2019)
    Suomessa tulehduksellisten suolistosairauksien esiintyvyys on kasvussa. Yksi toissijaisista lääkkeistä sairauteen on biologinen lääke infliksimabi, joka on TNF-alfa-estäjä. TNF-alfa on tärkeä sytokiini tulehduksellisissa sairauksissa. Infliksimabista vain noin 1/3 saa hyvän hoitovasteen. 1/3 ei saa vastetta ollenkaan, ja 1/3 menettää saadun vasteen, eikä vastetta osata ennustaa. Tämän tutkimuksen tarkoituksena oli etsiä biomarkkereita geeniekspressioprofiileista RNA-sekvensoinnilla ja ymmärtää erilaisten lääkevasteiden eroja. Tutkielmassa tutkittiin 15 potilaan veren valkosolujen geeniekspressioita ennen (0vk) ja jälkeen (12vk) infliksimabihoidon, sekä verrattiin vasteensaajien ja ei-vasteensaajien geeniekspressioiden profiileja. RNA eristettiin näytteistä, sekvensoitiin ja analysoitiin Chipster-ohjelmalla. Ekspressiotasot erosivat merkitsevästi aikapisteiden välillä 17 geenin osalta, joista tärkein on DUSP2-geeni. DUSP2 laskee epäsuorasti interleukiini-17 pitoisuutta, jolloin tulehdusreaktio vaimenee. Verrattaessa vasteensaajien ja osittaisen vasteensaajien geeniekspressioprofiileja ennen ja jälkeen hoidon, ei selvää trendiä näkynyt geenien ilmentymisessä. Tutkimuksessa ei ollut mukana 12 viikon näytteitä ei-vasteensaajilla, joten siihen ei voitu verrata. Tässä tutkimuksessa ei löytynyt biomarkkeria infliksimabin hoitovasteen ennustamiselle, mutta saatiin tärkeää tietoa DUSP2-geenin aktiivisuudesta. Kaikilla infliksimabihoidon saaneilla DUSP2- geenin ekspressio nousi veressä.
  • Junkkari, Sofia; Kolho, Kaija-Leena (2021)
    Lähtökohdat : Tavoitteena oli tarkastella TNF-α:n salpaaja infliksimabin aloitushoidon aikaansaamaa vastetta tulehduksellista suolistosairautta sairastavilla lapsilla. Menetelmät : Tutkimuksessa oli mukana 20 Crohnin tautia, 5 haavaista koliittia ja 5 välimuotoista koliittia sairastavaa lasta. Kuuden viikon aloitushoidon aikana potilaat saivat kolme infliksimabi-infuusiota. Hoitovastetta mitattiin ulosteen kalprotektiinin avulla. Tulokset : Kalprotektiinin mediaani hoitojakson alussa oli 908 µg/g, kahden viikon kuluttua mediaani oli laskenut merkitsevästi tasolle 295 µg/g (p = 0,005). Kuuden viikon jälkeen mediaani oli 256 µg/g, eikä ero kahden viikon arvoon ollut tilastollisesti merkitsevä. Vain Crohnin tautia sairastavilla kalprotektiinin mediaani laski tilastollisesti merkitsevästi (p = 0,0057). Potilaista 87 % jatkoi ylläpitohoitoon infliksimabilla. Päätelmät : Infliksimabi laski osalla potilaista tehokkaasti kalprotektiinitasoa jo kahden viikon jälkeen hoidon aloittamisesta. Crohnin tautia sairastaville saatiin parempi vaste kuin haavaisessa tai välimuotoisessa koliitissa.
  • Hamalainen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena (2011)
  • Kaski, Hanne-Kaisa; Turunen, Sami; Kolho, Kaija-Leena; Kulmala, Petri (2016)
    • Kroo­ninen tuleh­duk­sel­linen suolis­to­tauti (inflam­ma­tory bo­wel di­sease, IBD) on yleensä lap­silla aggres­sii­vi­sempi kuin aikui­silla, ja tau­din var­hainen totea­minen on tär­keää nor­maalin kas­vun ja kehi­tyksen turvaa­mi­seksi. • Lapsi­po­ti­laiden hoi­dossa on tär­keää myös moniu­lot­teinen hoi­to, jo­ka si­sältää ravit­se­muksen, lääke­hoidon ja hen­kisen hoi­don se­kä tau­din kompli­kaa­tioiden hy­vän hoi­don. • Paran­tavaa lääke­hoitoa ei ole, vaan lääki­tyksen tarkoi­tuk­sena on rau­hoittaa tuleh­dusta, es­tää pahe­ne­mis­vai­heita ja hel­pottaa tau­din oi­reita. • Biolo­giset lääk­keet ovat mullis­taneet vai­kean tuleh­duk­sel­lisen suolis­to­taudin hoi­don, ja uu­sia lääk­keitä ­ke­hi­tetään jatku­vasti. • Edelleen tar­vitaan myös kirur­gista hoi­toa.
  • BLING Res Grp; Lamberg, Tea; Sipponen, Taina; Valtanen, Sanna; Eklund, Kari K.; Mälkönen, Tarja; Aalto, Kristiina; Mikola, Katriina; Kolho, Kaija-Leena; Leinonen, Sanna; Isomäki, Pia; Mäkinen, Heidi; Vidqvist, Krista-Liisa; Kokko, Arto; Huilaja, Laura; Kyllönen, Minna; Keskitalo, Paula; Sard, Sirja; Vähäsalo, Paula; Koskela, Ritva; Kröger, Liisa; Lahtinen, Perttu; Haapala, Anna-Maija; Korkatti, Katja; Sokka-Isler, Tuulikki; Jokiranta, T. Sakari (2022)
    Introduction The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1-3 months). Conclusion Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.
  • Eberl, Anja; Huoponen, Saara; Pahikkala, Tapio; Blom, Marja; Arkkila, Perttu; Sipponen, Taina (2017)
    Background: Clinical use of biosimilar infliximab (CT-P13) in inflammatory bowel diseases (IBDs) is based on extrapolation of indication from clinical studies performed in rheumatological diseases. Only few data exist of behaviour of infliximab trough levels (TLs) and anti-drug antibodies (ADAs) during switching.Aim: The objective of this study was to evaluate changes in TLs, ADA formation and disease activity after switching from originator infliximab to biosimilar one.Methods: All our IBD patients receiving maintenance infliximab therapy were switched to biosimilar infliximab. TLs and ADAs were measured before the last originator infusion and before the third biosimilar infusion. Laboratory values, disease activity indices (partial Mayo score and Harvey-Bradshaw index) and demographic data were collected from patient records.Results: A total of 62 patients were included in the final analysis (32 Crohn's disease, 30 ulcerative colitis (UC) or IBD-unclassified). No significant changes in median TLs before (5.5mg/l) and after switching (5.5mg/l, p=.05) occurred in the entire study group or in the Crohn's disease (CD) subgroup (5.75 and 6.5mg/l, p=.68). However, in the subgroup of ulcerative colitis, the change in median TL was significantly different (from 5.2 to 4.25mg/l, p=.019). Two patients developed ADAs after switching. No changes in disease activity were detected during switching and no safety concerns occurred.Conclusions: Switching from originator to biosimilar infliximab resulted in statistically significant differences in infliximab TLs in patients with UC but not in patients with Crohn's disease. The clinical significance for this difference is doubtful and in neither group changes in disease activity occurred.
  • Ventin-Holmberg, Rebecka; Höyhtyä, Miikka; Saqib, Schahzad; Korpela, Katri; Nikkonen, Anne; Salonen, Anne; de Vos, Willem M.; Kolho, Kaija Leena (2022)
    Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.