BACKGROUND/AIMS: Originator-adalimumab, an established treatment for patients with Crohn's disease (CD), showed no difference in efficacy or adverse events versus adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks (W) of treatment. To understand the long-term effectiveness of SB5-adalimumab in CD, patients switched from originator-adalimumab to SB5-adalimumab were compared with patients remaining on originator-adalimumab over 104 W. METHODS: Data on patients aged ≥18 years, diagnosed with CD and treated at ISCARE, were collected prospectively from July 2018 to January 2021. Primary outcome: clinical disease activity at W52, measured by Harvey-Bradshaw index (HBI). Secondary outcomes: C-reactive protein (CRP), faecal calprotectin (FC) and adalimumab concentrations at W10, 26, 52 and 104, and treatment persistence. To ensure comparable cohorts, patients were propensity score (PS)-matched for age, gender and disease activity. RESULTS: After matching, 54 patients remained per cohort. At W52, mean (SD) HBI score was 3.2 (2.5) for originator-adalimumab and 4.0 [3.6] for SB5-adalimumab (difference [95% CI] -0.78 [-2.8, 1.3]; n = 18/cohort); no clinically meaningful differences in CRP, FC or drug concentrations were noted. Kaplan-Meier's estimates (95% CI) of remaining on treatment were originator-adalimumab: 0.870 (0.785-0.965) versus SB5-adalimumab: 0.648 (0.533-0.789) at W52 and significantly lower for SB5-adalimumab versus originator-adalimumab (p < .001) over 104 W. Local skin reaction events/pain was the main reason for treatment discontinuation in the SB5-adalimumab cohort (n = 20/54 [37%]). CONCLUSIONS: These long-term results of CD patients receiving originator-adalimumab or following nonmedical switch to SB5-adalimumab show similar therapeutic effects on clinical disease activity, biological parameters and pharmacokinetic profile in both cohorts from 52 to 104 W. A separation in persistence was observed beyond W26, mainly due to differences in local reactions at the injection site.
- MeSH
- adalimumab škodlivé účinky MeSH
- biosimilární léčivé přípravky * škodlivé účinky MeSH
- Crohnova nemoc * chemicky indukované farmakoterapie MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé MeSH
- mladiství MeSH
- tendenční skóre MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Patients' perspectives after switching from originator to biosimilar adalimumab have yet to be assessed. We evaluated the efficacy of switching from the originator adalimumab to a biosimilar compound [SB5] in patients with inflammatory bowel disease [IBD]. METHODS: Data on IBD patients who were switched from the originator to biosimilar adalimumab [SB5] at IBD Center ISCARE were analysed. Disease activity was assessed using standard clinical indices (Harvey-Bradshaw index [HBI] for Crohn's disease [CD] and partial Mayo score for ulcerative colitis [UC]), and laboratory parameters (C-reactive protein [CRP] and faecal calprotectin [FC]). Trough levels and anti-drug antibodies were measured. Patients were evaluated 10 weeks [W10] after the switch, and results were compared with the control group of patients on originator compound. RESULTS: A total of 93 patients switched to biosimilar adalimumab were included [CD 86%] and were matched to 93 controls for age, gender, diagnosis, and disease activity. There was no difference in the disease activity in either SWITCH or ORIGINATOR cohorts between Weeks 0 and 10. Similarly, no difference was found between cohorts at both prespecified time points. Moreover, no significant differences in CRP or FC concentrations were seen between W0 and W10 either in the SWITCH, or in the ORIGINATOR cohort [p >0.05]. Adalimumab serum trough levels remained stable after the switch. No new safety signals were detected. CONCLUSIONS: Our study confirmed that switching IBD patients from the originator adalimumab to a biosimilar compound [SB5] does not affect treatment efficacy.
- MeSH
- adalimumab krev imunologie terapeutické užití MeSH
- biosimilární léčivé přípravky krev terapeutické užití MeSH
- C-reaktivní protein metabolismus MeSH
- centra terciární péče MeSH
- Crohnova nemoc krev farmakoterapie MeSH
- dospělí MeSH
- feces chemie MeSH
- gastrointestinální látky krev imunologie terapeutické užití MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada léků MeSH
- protilátky krev MeSH
- retrospektivní studie MeSH
- stupeň závažnosti nemoci MeSH
- ulcerózní kolitida krev farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Vancomycin-resistant enterococci (VRE) are nosocomial pathogens of increasing medical importance. This study involved 121 VRE selectively obtained from a representative set of 1464 samples collected from various sources in the north-eastern part of the Czech Republic. In total, 119 VRE belonged to Enterococcus faecium and two to Enterococcus faecalis. All isolates of E. faecium were resistant to at least three antibiotic classes. The resistance genes vanA, erm(B), tet(M), tet(L), aac(3)-IIIa and aac(6')-aph(2'') were detected. We assigned the E. faecium to sequence types ST5, ST18, ST38, ST64, ST92, ST273, ST549 and ST640. In E. faecium isolates, we identified the presence of replicases rep20pLG1 , rep2pRE25 , rep17pRUM , rep21pVEF1/2 and rep14pRI1 , as well as relaxases relpEF1 , relpLG1 , relpCIZ2 , relpRE25 and relpRUM . The presence of the toxin-antitoxin system axe-txe was detected mainly among isolates of hospital origin. The A and D types of transposon Tn1546 were those occurring most frequently. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first extensive study of vancomycin-resistant enterococci of diverse origin in a single well-defined area of the Czech Republic. The isolates were investigated for their antibiotic resistance, epidemiological characteristics and plasmid characteristics. Based on the results obtained, we can make assumptions as to the ways that vancomycin resistance is disseminated throughout the environment including humans and animals.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální proteiny genetika MeSH
- Enterococcus faecalis účinky léků genetika izolace a purifikace MeSH
- Enterococcus faecium účinky léků genetika izolace a purifikace MeSH
- enterokoky rezistentní vůči vankomycinu klasifikace genetika izolace a purifikace MeSH
- grampozitivní bakteriální infekce epidemiologie mikrobiologie MeSH
- lidé MeSH
- plazmidy genetika MeSH
- rezistence na vankomycin genetika MeSH
- systémy toxin-antitoxin genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. METHODS: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. RESULTS: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. CONCLUSION: Switching of IBD patients from original to biosimilar IFX is effective and safe.
- MeSH
- biosimilární léčivé přípravky terapeutické užití MeSH
- C-reaktivní protein analýza MeSH
- Crohnova nemoc terapie MeSH
- dospělí MeSH
- feces chemie MeSH
- gastrointestinální látky terapeutické užití MeSH
- idiopatické střevní záněty terapie MeSH
- indukce remise MeSH
- infliximab terapeutické užití MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- monoklonální protilátky terapeutické užití MeSH
- náhrada léků * MeSH
- retrospektivní studie MeSH
- střevní sliznice účinky léků MeSH
- ulcerózní kolitida terapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The production and use of chlorophenolic compounds in industry has led to the introduction of many xenobiotics, among them chlorophenols (CPs), into the environment. Five CPs are listed in the priority pollutant list of the U.S. EPA, with pentachlorophenol (PCP) even being proposed for listing under the Stockholm Convention as a persistent organic pollutant (POP). A green procedure for degrading such pollutants is greatly needed. The use of ferrate could be such a process. This paper studies the degradation of CPs (with an emphasis on PCP) in the presence of ferrate both in a spiked demineralized water system as well as in real contaminated groundwater. Results proved that ferrate was able to completely remove PCP from both water systems. Investigation of the effect of ferrate purity showed that even less pure and thus much cheaper ferrate was applicable. However, with decreasing ferrate purity, the degradability of CPs may be lower.
Regarding environmental pollution, the greatest public and scientific concern is aimed at the pollutants listed under the Stockholm Convention. These pollutants are not only persistent but also highly toxic with a high bioaccumulation potential. One of these pollutants, γ-hexachlorocyclohexane (γ-HCH), has been widely used in agriculture, which has resulted in wide dispersion in the environment. Remediation of this persistent and hazardous pollutant is difficult and remains unresolved. Of the many different approaches tested, to date, none has used ferrates. This is unexpected as ferrates are generally believed to be an ideal chemical reagent for water treatment due to their strong oxidation potential and the absence of harmful by-products. In this paper, the degradation/transformation of HCHs by ferrates under laboratory conditions was studied. HCH was degraded during this reaction, producing trichlorobenzenes and pentachlorocyclohexenes as by-products. A detailed investigation of pH conditions during Fe(VI) application identified pH as the main factor affecting degradation. We conclude that ferrate itself is unreactive with HCH and that high pH values, produced by K₂O impurity and the reaction of ferrate with water, are responsible for HCH transformation. Finally, a comparison of Fe(VI) with Fe(0) is provided in order to suggest their environmental applicability for HCH degradation.
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- Burkholderia cepacia komplex izolace a purifikace MeSH
- Burkholderia MeSH
- infekce bakteriemi rodu Burkholderia epidemiologie mikrobiologie MeSH
- infekce spojené se zdravotní péčí epidemiologie mikrobiologie MeSH
- lidé MeSH
- nemocnice MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
