219 research outputs found
The impact of biologics on health-related quality of life in patients with inflammatory bowel disease
Lauran Vogelaar1, Adriaan van’t Spijker2, C Janneke van der Woude11Department of Gastroenterology and Hepatology, 2Department of Psychology and Psychotherapy, Erasmus Medical Centre, RotterdamBackground: Inflammatory bowel disease (IBD) is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL). A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.Objective: To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.Methods: We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH). Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.Results: Out of 202 identified articles, 8 randomized controlled trials (RCT) met the inclusion criteria. Two RCTs on infliximab showed significant improvement of HRQoL compared to placebo which was sustained over the long term. One RCT on adalimumab showed a significant and sustained improvement of HRQoL compared to placebo. This study showed also significant decrease of fatigue in the adalimumabtreated patients. Three RCTs on certolizumab showed a significant improvement of HRQoL in the intervention group compared to placebo. Two RCTs of natalizumab treatment were found. One study showed significant and sustained improvement compared to placebo, and also scores of HRQoL comparable to that in the general population, but in the other no significant results were found.Conclusion: The biologics infliximab, adalimumab, certolizumab, and natalizumab demonstrated significant improvement of HRQoL of IBD patients compared with placebo. However, we found differences in improvement of HRQoL between the different biologics.Keywords: inflammatory bowel disease, health-related quality of life, health care costs, biologic
Lipid Profiles in Patients with Ulcerative Colitis Receiving Tofacitinib - Implications for Cardiovascular Risk and Patient Management
Biomarkers predicting the effect of anti-TNF treatment in paediatric and adult inflammatory bowel disease
Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients. Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD.Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response. Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD.</p
Impact of the Coronavirus Disease Pandemic on Health-Related Quality of Life of Patients with Inflammatory Bowel Disease
BACKGROUND: To learn from the crisis caused by the coronavirus disease (COVID-19) pandemic and be prepared for future pandemics, it is important to investigate the impact of this period on the wellbeing of patients with inflammatory bowel disease (IBD). AIMS: To describe the health-related quality of life (HRQoL) and disease control of IBD patients during the first wave of the COVID-19 pandemic in The Netherlands. METHODS: Between March 17 and July 1, 2020, patients aged 18 years and older with IBD from the Erasmus MC (Rotterdam, The Netherlands) were invited to complete online questionnaires at week 0, 2, 6 and 12. The Inflammatory Bowel Disease Questionnaire (IBDQ), the Inflammatory Bowel Disease Control-8 (IBD-control-8) and the numeric rating scale on fatigue were used. The evolution of the different outcomes over time was measured using mixed models. RESULTS: Of 1151 invited patients, 851 patients (67% CD and 33% UC or IBD-U) participated in the study (response rate 74%). No relevant changes in total scores were found over time for the IBDQ (effect estimate 0.006, 95% CI [− 0.003 to 0.015]) and IBD-control-8 (effect estimate 0.004, 95% CI [0.998–1.011]). There was a slight, increasing trend in fatigue scores over time (effect estimate 0.011, 95% CI [0.004, 0.019]). CONCLUSIONS: This first lock down due to the COVID-19 pandemic in The Netherlands did not impact on the HRQoL and disease control of patients with IBD. Up to date information may have contributed to a stable HRQoL in IBD patients even in an extreme period with restrictions and insecurities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10620-021-07118-8
Role of defective autophagia and the intestinal flora in Crohn disease
The precise mechanisms underlying the development of Crohn disease (CD) remain controversial, but sufficient data have been collected to suggest that an uncontrolled immune response within the intestinal mucosa leads to inflammation in a genetically susceptible host. Although lack of mucosal regulatory T cells causes colitis in humans and experimental rodents, patients with CD have more rather than less regulatory activity in the intestine, apparently excluding defects in tolerance as the cause of CD. Genome-wide association studies have identified many gene variants that confer susceptibility and which seem associated to diminished functioning of especially innate immunity. In apparent agreement, CD patients are impaired with respect to innate immune responses and controlling bacterial flora in the intestine. Furthermore, severe genetic deficiencies in innate immunity, like e.g., lack of NADP oxidase activity or diminished function of the Wiskott Aldrich syndrome protein are associated with colitis in mice and men, and are often mistakenly diagnosed as CD. Thus we favor the view that the primary defect in CD is a lack in innate immunity, causing second tier immunological defenses to combat otherwise easily controlled bacterial breaches of the mucosal barrier.</p
SARS-CoV-2 breakthrough infections after COVID-19 vaccination in patients with inflammatory bowel disease:a systematic review and meta-analysis
Background: Patients with inflammatory bowel disease (IBD) have an attenuated serologic response to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of severe COVID-19. Objectives:To evaluate SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients. Design: A systematic literature search and meta-analysis was performed. Data sources and methods: The search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and CINAHIL. The articles were independently screened and selected by two reviewers. A random-effects model was used to calculate the pooled relative risk for breakthrough infections in vaccinated IBD patients and controls. Results: A total of 16 studies were included, with study periods ranging from January 2020 to October 2021 and follow-up time from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in vaccinated IBD patients. The disease course of COVID-19 was generally mild, with low hospitalization and mortality rates (0–8.7% and 0–4.3%, respectively). Vaccinated IBD patients had a significantly lower relative risk of breakthrough infection rate compared to unvaccinated controls (risk ratio: 0.07, 95% CI: 0.03–0.18). No difference was observed between IBD patients and non-IBD controls, and between partially and fully vaccinated IBD patients. The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. Most studies showed no impact from immunosuppressive treatment, anti-tumour necrosis factor alpha or corticosteroids and other biologics; one study reported higher rates for patients treated with infliximab versus vedolizumab. Conclusion: Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time. Registration: The protocol was published in the PROSPERO database (CRD42021292853).</p
Role of defective autophagia and the intestinal flora in Crohn disease
The precise mechanisms underlying the development of Crohn disease (CD) remain controversial, but sufficient data have been collected to suggest that an uncontrolled immune response within the intestinal mucosa leads to inflammation in a genetically susceptible host. Although lack of mucosal regulatory T cells causes colitis in humans and experimental rodents, patients with CD have more rather than less regulatory activity in the intestine, apparently excluding defects in tolerance as the cause of CD. Genome-wide association studies have identified many gene variants that confer susceptibility and which seem associated to diminished functioning of especially innate immunity. In apparent agreement, CD patients are impaired with respect to innate immune responses and controlling bacterial flora in the intestine. Furthermore, severe genetic deficiencies in innate immunity, like e.g., lack of NADP oxidase activity or diminished function of the Wiskott Aldrich syndrome protein are associated with colitis in mice and men, and are often mistakenly diagnosed as CD. Thus we favor the view that the primary defect in CD is a lack in innate immunity, causing second tier immunological defenses to combat otherwise easily controlled bacterial breaches of the mucosal barrier.</p
Low dose Naltrexone for induction of remission in inflammatory bowel disease patients
Background: Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Methods: Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Results: Low dose Naltrexone induce
Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population
AIMS: Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We compared cardiovascular disease (CVD) risk factors and 10-year risk in IBD patients to the general population. METHODS AND RESULTS: In this cross-sectional study, consecutive IBD patients ≥45 years were included. History of ASCVD and CVD risk factors (smoking, hypertension, overweight, hypercholesterolaemia, diabetes, and metabolic syndrome) were assessed. The Systematic COronary Risk Evaluation (SCORE2) algorithm was used to estimate 10-year CVD risk. One to four age/sex-matched controls were derived from the prospective population-based Rotterdam Study cohort. In total, 235 IBD patients were included {56% women, median age 59 years [interquartile range (IQR) 51-66]} and matched to 829 controls [56% women, median age 61 years (IQR 56-67)]. Inflammatory bowel disease patients experienced ASCVD events more often compared with matched controls [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.23-3.27], specifically heart failure (OR 2.02, 95% CI 1.02-4.01) and coronary heart disease (OR 2.01, 95% CI 1.7-3.13). Inflammatory bowel disease patients showed lower odds of overweight (OR 0.48, 95% CI 0.35-0.66) and hypercholesterolaemia (OR 0.45, 95% CI 0.31-0.65) and higher odds of hypertension (OR 1.67, 95% CI 1.19-2.32), as well as higher waist circumference (+4 cm, P = 0.006) and triglyceride levels (+0.6 mmol/L, P < 0.001) as compared with controls. Mean 10-year CVD risk was 4.0% [standard deviation (SD) ±2.6] in 135 IBD patients vs. 6.0% (SD ±1.6) in 506 controls. CONCLUSION: The increased CVD risk in IBD is discrepant with the 10-year CVD risk estimate. Systematic COronary Risk Evaluation may underestimate CVD risk in IBD patients due to differing CVD risk profiles compared with the general population, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of hypertension, abdominal obesity, and hypertriglyceridaemia.</p
Intestinal resection rates in Crohn's disease decline across two different epidemiological areas: A consistent observation not merely due to introduction of anti-TNFα
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