Summary
Background
There is an increasing body of evidence showing that earlier use of biologics improves clinical outcomes in Crohn's disease (CD).
Aim
To perform a systematic review and ...meta‐analysis to assess the impact of early biologic use in the treatment of CD.
Methods
PubMed and Embase databases were searched for English language papers and conference s published through April 30, 2019. Studies were selected for inclusion if patients initiated biologics within 2 years of a CD diagnosis or if earlier biologics use (top‐down) was compared with a conventional step‐up strategy. Random‐effects meta‐analyses were conducted to compare clinical remission (CR), relapse and endoscopic healing rates between early biologic treatment (<2 years of disease duration or top‐down treatment strategy) and late/conventional treatment (biologic use after >2 years of disease duration or conventional step‐up treatment strategy).
Results
A total of 3069 records were identified, of which 47 references met the selection criteria for systematic review. A total of 18 471 patients were studied, with a median follow‐up of 64 weeks (range 10‐416). Meta‐analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 95% CI: 1.69‐2.60, n = 2763, P < .00001), lower relapse rates (OR 0.31 95% CI: 0.14‐0.68, n = 596, P = .003) and higher mucosal healing rates (OR 2.37 95% CI: 1.78‐3.16, n = 994, P < .00001) compared with late/conventional management.
Conclusions
Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real‐world settings.
Abstract
Background and Aims
Management of Crohn’s disease and ulcerative colitis has typically relied upon treatment intensification driven by symptoms alone. However, a ‘treat-to-target’ management ...approach may help to address underlying inflammation, minimise disease activity at early stages of inflammatory bowel disease, limit progression, and improve long-term outcomes.
Methods
A systematic literature review was conducted to identify data relevant to a treat-to-target approach in inflammatory bowel disease, published between January 1, 2007 and May 15, 2017.
Results
Consistent with recommendations of the Selecting Therapeutic Targets in Inflammatory Bowel Disease STRIDE working group, studies have investigated factors influencing the achievement of both endoscopic and histological mucosal healing and patient-level outcomes in inflammatory bowel disease IBD. Histological healing and biomarker levels have also been shown to be modifiable outcomes. Although there is a lack of prospectively derived evidence validating mucosal healing as a treatment target, data are emerging to suggest that targeting mucosal healing or inflammation rather than symptoms may be cost-effective in some settings. The review highlighted several strategies that may support the implementation of a treat-to-target approach in IBD. The prospective randomised CALM study demonstrated how tight control whereby treatment decisions are based on close monitoring of inflammatory biomarkers leads to improvements in endoscopic and clinical outcomes. The review also considered the influence of coordinated care from a multidisciplinary team and patient engagement with improved adherence, as well as the role of therapeutic drug monitoring in inflammatory bowel disease management.
Conclusions
A treat-to-target strategy may impact on disease progression and improve outcomes in inflammatory bowel disease. Prospective studies including long-term data are required to ensure that the most appropriate targets and strategies are identified.
Summary
Background
Crohn's disease has a substantial negative impact on health‐related quality of life (HRQoL).
Aim
To examine the effects of risankizumab on HRQoL in Crohn's disease
Methods
We ...analysed data from patients with Crohn's disease from 12‐week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52‐week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F), 36‐item Short Form Health Survey (SF‐36), EuroQol 5‐Dimension‐5‐Level (EQ‐5D‐5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52.
Results
At week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT‐F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p < 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF‐36 physical and mental component summary scores, EQ‐5D‐5L and activity impairment within work productivity measures.
Conclusions
Risankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease‐specific and general patient‐reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy.
IBDQ remission and fatigue and SF‐36 PCS responses after 52 weeks of maintenance therapy with risankizumab in patients with Crohn's disease.
Maintaining spatial orientation when carrying out goal-directed movements requires an animal to perform angular path integration. Such functionality has been recently demonstrated in the ellipsoid ...body (EB) of fruit flies, though the precise circuitry and underlying mechanisms remain unclear. We analyze recently published cellular-level connectomic data and identify the unique characteristics of the EB circuitry, which features coupled symmetric and asymmetric rings. By constructing a spiking neural circuit model based on the connectome, we reveal that the symmetric ring initiates a feedback circuit that sustains persistent neural activity to encode information regarding spatial orientation, while the asymmetric rings are capable of integrating the angular path when the body rotates in the dark. The present model reproduces several key features of EB activity and makes experimentally testable predictions, providing new insight into how spatial orientation is maintained and tracked at the cellular level.Ellipsoid body (EB) neurons in the fruit fly represent the animal heading through a bump-like activity dynamics. Here the authors report a connectome-driven spiking neural circuit model of the EB and the protocerebral bridge (PB) that can maintain and update an activity bump related to the spatial orientation.
Aims
The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity ...for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population‐based manner.
Methods
We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non‐infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.
Results
The study cohort comprised 71 379 ATD initiators, with a median follow‐up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person‐years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person‐years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89‐fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08‐fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio HR 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).
Conclusions
MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose‐dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.
Based on the concept of "governance through scientism", this article aims to reveal the tacit practices of the institutional culture of scientism among Taiwan Biobank's elite scientists, whose ...imaginaries have shaped the dominance of a deficit model of the public in dealing with public controversy and establishing regulatory mechanisms. Examining three periods of ELSI controversies from 2000 to 2021, we identify three types of scientific imaginaries of publics, namely the silent public (2000-2004), the anti-science public (2005-2010), and the EGC as the lawful public supervisory body (2010-2021). In 2010, the Human Biobank Management Act (HBMA) was passed in Taiwan as a solution to public controversy and as a strategy to bypass public engagement. However, the overemphasis on formative legislation caused actors to overlook the processual approach in which ongoing critical reflections are required for the changing operations of TBB
Anti-vascular endothelial growth factors (VEGFs) treatment has been associated with an increased risk of thromboembolic events. Therefore, the use of anti-VEGFs for patients with colorectal cancers ...(CRC) has raised concerns about the potential risk of retinal vein occlusion (RVO), an ocular disease caused by embolism or venous stasis. This study aims to evaluate the risk of RVO in patients with CRC treated with anti-VEGFs.
We conducted a retrospective cohort study using the Taiwan Cancer Registry and National Health Insurance Database. The study cohort comprised patients newly diagnosed with CRC between 2011 and 2017, who received anti-VEGF treatment. For each patient in the study cohort, a control group comprising four patients newly diagnosed with CRC, but not receiving anti-VEGF treatment, was randomly selected. A washout period of 12 months was implemented to identify new cases. The index date was defined as the date of the first prescription of anti-VEGF drugs. The study outcome was the incidence of RVO, as identified by ICD-9-CM (362.35 and 362.36) or ICD-10-CM codes (H3481 and H3483). Patients were followed from their index date until the occurrence of RVO, death or the end of the study period. Covariates, including patients' age at index date, sex, calendar year of CRC diagnosis, stage of CRC and comorbidities related to RVO, were included. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with adjustments for all covariates to compare the risk of RVO between the anti-VEGF and control groups.
We recruited 6285 patients in the anti-VEGF group and 37,250 patients in the control group, with mean ages of 59.49 ± 12.11 and 63.88 ± 13.17 years, respectively. The incidence rates were 1.06 per 1000 person-years for the anti-VEGF group, and 0.63 per 1000 person-years for the controls. There was no statistically significant difference in RVO risk between the anti-VEGF and control groups (HR: 2.21, 95% CI: 0.87-5.61).
Our results indicated no association between use of anti-VEGF and occurrence of RVO among CRC patients, although the crude incidence rate of RVO was higher in patients receiving anti-VEGF, compared to control patients. Future study with larger sample size is required to confirm our findings.
Abstract
Objectives
TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking ...for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA.
Methods
We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios for infection associated with TNFIs compared with DMARDs, adjusting for potential confounders with high-dimensional propensity scores and time-varying CS use.
Results
We identified 2013 DMARD initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days, respectively. We identified 18 and 11 patients with a serious infection in the DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and 2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models, TNFIs were associated with an increased risk of serious bacterial infection compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86).
Conclusion
Use of TNFIs poses a higher risk of serious infection compared with DMARDs in children with JIA. Our analysis confirms the US Food and Drug Administration warning about TNFI-associated infection in children with JIA.
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