No study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn's disease (CD). The aim of the study was to compare the efficacy of ...biologics in this setting.
Patients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study.
Among the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14-24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively, p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml.
VDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-ups ...of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy was evaluated in intestinal tissue.
Forty-two consecutive patients (sex ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were included prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines.
Sixteen patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue; all of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7; 95% confidence interval: 1.2-22.5). A CMV DNA load above 250 copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+=4.33; area under the receiver-operating characteristic curve=0.85). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir; a clinical remission was observed in seven cases, with a sustained response in five of them.
The CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC. Initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.
Background. Monitoring of biological TNF inhibitors is a very important tool to guide clinical decisions using specialized algorithms, especially in gastroenterology. A new chemiluminescent ...instrument (i-TRACK10® from Theradiag) could replace ELISA techniques to calculate the dosage of drugs and anti-drug antibodies. In this bi-centric study, we explored the analytical performances of i-TRACK10® using manual or automated (DS2®) ELISA Lisa-Tracker® assays, and compared the results. Patients and methods. Intra- and inter-run performances were evaluated with i-TRACK10® in two different laboratories and for two different ranges of values for infliximab, adalimumab, and their respective antibodies. Patients’ samples were used in the labs to compare the results obtained between the new instrument and either the manual Lisa-Tracker® or the automated DS2. Results. Intra- and inter-run performances were satisfactory, with values between 1.8% and 16.1% (for inter-run imprecision at low/medium values of infliximab). Results were generally comparable between assays. with the lowest value of correlation at 0.59 (anti-adalimumab dosage between i-TRACK10® and manual ELISA). Most often, values of drugs and anti-drug antibodies were higher with i-TRACK10® than with manual ELISA assay, and correlation values were better with automated ELISA. Agreements were globally acceptable, and the lowest coefficients of 0.7 was obtained for adalimumab values between i-TRACK10® and the two ELISA methods, and for anti-adalimumab values between i-TRACK10® and manual ELISA. The type of assay can potentially induce a change in the class of patients and lead to divergent therapeutic decisions. Conclusions. The new random-access instrument i-TRACK10® presents many advantages in a routine laboratory: rapidity, the possibility of standardization, usability, and expansion of the measurement range. Despite the relatively good agreement of results, it is preferable to use the same assay in longitudinal follow-up of a patient, because quantitative results were not completely equivalent especially for anti-drug antibodies.
Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the ..."microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used
and
models, their implications, and perspectives in the field based on a systematic review of PubMed. Applications of various animal models (zebrafish, mouse, canine, rat, rabbit) to microbiota-gut-brain axis research with practical examples of
methods and innovative approaches to studying gut-brain communications are highlighted. In particular, we extensively discuss the potential of "organ-on-a-chip" devices and their applications in this field. Overall, this review sheds light on the most widely used models and methods, guiding researchers in the rational choice of strategies for studies of microbiota-gut-brain interactions.
Introduction
The pharmacokinetic equivalence of dose intensification with adalimumab (ADA) 80 mg every other week (EOW) compared to weekly 40 mg has only been supported by modeling systems.
Aim of ...the Study
To compare the trough levels of ADA (TLA) and the occurrence of anti-ADA antibodies (AAA) between these two treatment regimens.
Patients and Methods
This was a prospective study including all consecutive patients with inflammatory bowel disease (IBD) who had reached a longstanding and deep remission under treatment with ADA 40 mg once a week. In these patients, the ADA regimen was changed from 40 mg/week to 80 mg EOW. TLA and AAA levels using a drug-tolerant assay were monitored before and ten weeks after from the change in the ADA regimen and the results compared by a Wilcoxon paired test.
Results
Sixty-two patients (60% CD, mean age 35 years) were included. Before and ten weeks after the changes of ADA regimen, the median TLA were (6.9 µg/mL versus 7.0 µg/mL, respectively;
P
= 0.34) and the AAA levels (3.4 µg/ml-eq versus 3.0 µg/ml-eq, respectively;
P
= 0.25.) were quite similar. Likewise, quartiles of TLA (Kendall test
r
= 0.91;
P
< 0.001) and AAA (
r
= 0.78;
P
< 0.001) did not differ before and after ADA regimen. When stratifying all the patients into 4 groups based on drug/antibody levels (immunogenic, subtherapeutic, therapeutic, or supratherapeutic), no patient needed for returning to the previous weekly regimen. In terms of acceptability, more than 60% of patients preferred an injection EOW compared once a week.
Conclusions
In IBD patients who achieved a deep clinical remission under ADA 40 mg once a week, the pharmacokinetic of ADA was similar when ADA regimen was changed to 80 mg EOW. Given the patient’s preference for the latter regimen, a modification of injection regimen should be systematically proposed.
About one-third of inflammatory bowel disease (IBD) patients still require surgery. A growing number of them receive anti-tumor necrosis factor (TNF) therapy before surgery. The present meta-analysis ...studied the risk of postoperative complications in IBD patients treated with anti-TNF.
MEDLINE was searched (up to January 2012) to identify observational studies reporting the prevalence of postoperative complications in IBD patients. The prevalence of overall, infectious, and non-infectious postoperative complications was extracted for all studies, and according to preoperative anti-TNF treatment where reported. Pooled prevalence, as well as odds ratios (ORs), with 95% confidence intervals (CIs) was calculated.
The search identified 86 citations. Twenty-one studies, containing 4251 subjects, reported the prevalence of postoperative complications according to preoperative anti-TNF treatment. Pooled prevalence of any postoperative complication was 21%, 35%, and 26% in Crohn's disease (CD), ulcerative colitis (UC) or inflammatory bowel disease unspecified (IBD-U) and IBD, respectively. The prevalence of any postoperative complication was increased in IBD patients who underwent preoperative anti-TNF therapy (OR: 1.25; 95% CI: 1.02–1.53). Pooled prevalence of infectious postoperative complications was 16%, 17%, and 15% in CD, UC/IBD-U and IBD, respectively. The prevalence of infectious postoperative complications was increased in CD patients who underwent preoperative anti-TNF therapy (OR: 1.45; 95% CI: 1.03–2.05). The confounding effect of concomitant therapies could not be studied.
Preoperative anti-TNF use slightly increases the occurrence of overall postoperative complications in IBD patients, and particularly infectious complications in CD patients. Postoperative complications are not increased in UC.
Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the ...past via contaminated blood and unsafe injections and continue to be a serious problem of public health.The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified:(1)infected patient to non-infected patient;(2)infected patient to non-infected health careworker(HCW);and(3)infected HCW to non infected patient.For each condition,the circumstances of contamination are described together with the means to prevent them.As a whole,the more important risk is represented by unsafe practices regarding injections,notably with the improper use of multidose vials used for multiple patients.The questions of occupational exposures and infected HCWs are also discussed.In terms of prevention and surveillance,the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares,with training programs and audits to verify their good application.HCWs must be sensitized to the risk of blood-borne pathogens,notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures.The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay.With the need to stay vigilant because HCV infection is often a hidden risk,it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.
Background
There are still controversial data regarding the prognostic value of Venous ThromboEmbolism (VTE) in advanced Pancreatic Ductal AdenoCarcinoma (PDAC) and thromboprophylaxis is poorly ...prescribed despite international recommendations.
Methods
Medical charts of patients consecutively treated for advanced PDAC from 2010 to 2019 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier method. Prognostic Factors were identified using a multivariate Cox’s proportional hazard model. Early VTE was defined as VTE occurring within the three months following the PDAC diagnosis.
Results
A total of 174 patients were included (median age: 67 years; males: 55.2%; performance status (PS) 0–1: 88.5%) with metastatic disease in 74.7%. At baseline, Khorana score was high (≥ 3) in the vast majority of cases (93.7%). The cumulative incidences of VTE were 12.4% (95% CI 7.3–17.2) at 3 months, 20.4% (95% CI 13.9–26.4) at 6 months and 28.1% (95% CI 20.0–35.3) at 12 months. Patients who experienced early VTE had shorter PFS (3.8 months vs. 7.1 months; HR = 2.02; 95% CI 1.21–3.37;
p
= 0.006) and shorter OS (8.0 months vs. 14.1 months; HR = 2.42; 95% CI 1.37–4.30;
p
= 0.002) compared to the others, independently of prognostic factors such as PS, liver metastases, carcinomatosis, and chemotherapy regimen.
Conclusion
early VTE is a strong prognostic factor in advanced PDAC and occurs in about one in 10 patients.
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