Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ''switch cohort'' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ''non-switch'' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9(hi), SSEA-1(−) Cells in Embryonic Stem Cell-Derived Embryoid Bodies

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(−) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(−) cells that constituted 1%–10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

How to incorporate patients preference into ulcerative colitis current clinical management: initial document from a Spanish multidisciplinary steering committee

Background To provide a patient-centred care in ulcerative colitis (UC), it is essential to address and to incorporate patient’s opinions, preferences, etc. Our aim was to define and integrate UC patient's preferences in the management of the disease in clinical practice. Methods Qualitative study. A review of the literature was carried out in Medline and in the Clinical Queries of PubMed. We performed primary searches with Mesh terms and free text to identify preferences of patients with UC as well as clinical scenarios that may determine specific preferences. We selected articles that included: patients with UC, adults, who analysed their preferences. Likewise, only the following designs were included: meta-analysis, systematic reviews, clinical trials, studies, observations, and qualitative studies. The quality of the studies was evaluated with the Oxford scale. The results of the literature review were presented and discussed in a nominal group meeting, composed by a multidisciplinary steering committee of 6 gastroenterologists, 1 primary care physician, 1 nurse, and 1 patient. After that, a series of clinical relevant scenarios were identified and related patient preferences were proposed for them. This was the base to the generation of a set of general recommendations. The level of agreement among the multidisciplinary steering committee with the recommendations was established in a Delphi process in which the members of the committee voted from 0 = totally disagree to 10 = totally agree. Agreement was defined if at least 70% of the participants voted ≥7. Results The review of the literature included 69 articles, most of them qualitative studies of moderate quality. UC patient’s preferences were classified according to different topics including information, treatment (pharmacological and non-pharmacological), disease follow-up, relations with health professionals, health system and with the administration. In the nominal group meeting several key clinical scenarios were identified: the diagnosis, follow-up, surgery and special clinical scenarios/patients profiles (children, teenagers, elderly, women, pregnancy and lactation, family, and socio-work environment). A total of 11 recommendations about the incorporation of UC patients into daily practice across the key clinical scenarios are were generated (see table). All of them reached the level of agreement establishe

Impact of co-morbidities on loss and lack of response to anti-TNFs in inflammatory bowel disease: VERNE study

Background Although anti-TNFα therapy is an effective approach for IBD, a great amount of patients does not respond to induction therapy and a significant proportion loses response over time, making it necessary to search for accurate prognostic markers to guide patient selection. This study aimed to evaluate the impact of the co-morbidities profile on the response to anti-TNFs in IBD patients treated in Spanish hospitals. Methods This was a retrospective, non-interventional, multi-centre (24 sites), observational study that included consecutive adult patients diagnosed with UC or CD who started treatment with biologics between June 2011 and June 2013. Data about patient characteristics, including comorbidities, were collected. Studied variables were analysed descriptively. Results Three hundred and ten patients with IBD were analysed, 194 with CD and 116 with ulcerative colitis. Average age was 44.9 years (SD: 13), 53.5% were male and most of them Caucasian (95.8%). CD locations were ileum and colon (44.6%), terminal ileum (37.3%), colon (15.5%) and upper gastrointestinal tract (2.6%); UC locations were extensive colitis (48.2%), left colitis (43.8%) and proctitis (8.0%). Most frequent comorbidities were: Chronic Obstructive Pulmonary Disease (COPD) (3.7%), connective tissue disease (3.0%), diabetes mellitus (2.3%), mild chronic hepatopathy (2.0%), myocardial infarction (1.7%), solid tumours (1.7%), congestive heart failure (1.3%) and cerebrovascular disease (1.3%). Logistic regression models showed that COPD was an independent factor associated with lack of response (OR 2.67 CI 95%: 1.33–5.35; p = 0.006), and myocardial infarction of loss of response (OR 3.30; CI 95%: 1.48–7.35; p = 0.003) to anti-TNF therapy. The concomitant use of corticosteroids was an additional independent factor associated with lack of response (OR 2.16; CI 95%: 1.25–3.73; p = 0.006) and loss of response (OR 2.45; CI 95%: 1.35–4.44; p = 0.003), and, in contrast, CD was a negative independent predictor of lack of response (OR 0.59; CI 95%: 0.37–0.93; p = 0.024) and loss of response (OR 0.58; CI 95%: 0.34–0.99; p = 0.044). Conclusions In this population of IBD patients who received first anti-TNF treatment, the most frequent comorbidities were COPD, connective tissue disease, diabetes and hepatopathies. Those associated with lack and loss of response were COPD and myocardial infarction, respectively. Results suggest that patients characteristics should be considered when selecting the optimal biological treatment for IBD patients