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Female reproductive health and inflammatory bowel disease: A practice-based review.
, , Armuzzi, A, Bortoli, A, Castiglione, F, Contaldo, A, Daperno, M, D'Incà, R, Labarile, N, Mazzuoli, S, Onali, S, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(1):19-29
Abstract
Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.
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Assessment of Vedolizumab Disease-Drug-Drug Interaction Potential in Patients With Inflammatory Bowel Diseases.
Sun, W, Lirio, RA, Schneider, J, Aubrecht, J, Kadali, H, Baratta, M, Gulati, P, Suri, A, Lin, T, Vasudevan, R, et al
Clinical pharmacology in drug development. 2021;(7):734-747
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Disease-drug-drug interactions (DDDIs) have been identified in some inflammatory diseases in which elevated proinflammatory cytokines can downregulate the expression of cytochrome P450 (CYP) enzymes, potentially increasing systemic exposure to drugs metabolized by CYPs. Following anti-inflammatory treatments, CYP expression may return to normal, resulting in reduced drug exposure and diminished clinical efficacy. Vedolizumab has a well-established positive benefit-risk profile in patients with ulcerative colitis (UC) or Crohn's disease (CD) and has no known systemic immunosuppressive activity. A stepwise assessment was conducted to evaluate the DDDI potential of vedolizumab to impact exposure to drugs metabolized by CYP3A through cytokine modulation. First, a review of published data revealed that patients with UC or CD have elevated cytokine concentrations relative to healthy subjects; however, these concentrations remained below those reported to impact CYP expression. Exposure to drugs metabolized via CYP3A also appeared comparable between patients and healthy subjects. Second, serum samples from patients with UC or CD who received vedolizumab for 52 weeks were analyzed and compared with healthy subjects. Cytokine concentrations and the 4β-hydroxycholesterol-to-cholesterol ratio, an endogenous CYP3A4 biomarker, were comparable between healthy subjects and patients both before and during vedolizumab treatment. Finally, a medical review of postmarketing DDDI cases related to vedolizumab from the past 6 years was conducted and did not show evidence of any true DDDIs. Our study demonstrated the lack of clinically meaningful effects of disease or vedolizumab treatment on the exposure to drugs metabolized via CYP3A through cytokine modulation in patients with UC or CD.
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Chyle leak following total colectomy for ulcerative colitis: a case report and review of the literature.
Brewer, CF, Al-Abed, Y
Annals of the Royal College of Surgeons of England. 2021;(7):e231-e233
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Chyle leak is a rare complication in colorectal surgery. It occurs due to disruption of the lymphatic drainage network in the abdomen or retroperitoneum. We describe the first reported case of chyle leak following total colectomy for inflammatory bowel disease. Our patient underwent total colectomy for severe ulcerative colitis not responsive to medical treatment. Four days postoperatively, a milky fluid was noted in the drainage bag. Analysis of the fluid confirmed chyle. The patient remained well and was successfully managed conservatively with a fat-free elemental diet and was discharged from hospital on day 12 postoperatively. A review of the literature suggests that conservative management with dietary modification is a common and effective management strategy; however, medical and surgical options exist for refractory cases.
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Breaking the therapeutic ceiling in drug development in ulcerative colitis.
Alsoud, D, Verstockt, B, Fiocchi, C, Vermeire, S
The lancet. Gastroenterology & hepatology. 2021;(7):589-595
Abstract
Increased knowledge of the intricate pathogenesis of ulcerative colitis has triggered an advance in drug development during the past two decades, resulting in the advent of several biological agents and small-molecule therapies. Although the increase in therapeutic options is positive, remission rates of patients with ulcerative colitis given new therapeutic agents in induction trials remain at a modest 20-30%, seemingly facing a so-called therapeutic ceiling. This therapeutic ceiling requires a critical appraisal and highlights the need for alternative strategies for drug development. In this Review, we objectively itemise the boundaries of therapeutic efficacy in ulcerative colitis, provide possible explanations for the shortcomings of current strategies, and propose solutions to achieve better therapeutic outcomes in ulcerative colitis.
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Efficacy of JAK inhibitors in Ulcerative Colitis.
Ferrante, M, Sabino, J
Journal of Crohn's & colitis. 2020;(Supplement_2):S737-S745
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Janus kinase [JAK] inhibitors are a completely novel therapy for the treatment of patients with immune-mediated inflammatory disorders. The oral formulation of tofacitinib has recently been approved for the treatment of moderate-to-severe ulcerative colitis. In the placebo-controlled OCTAVE programme, tofacitinib proved to be efficacious for both inducing and maintaining clinical remission, and this both in anti-tumour necrosis factor-naïve and exposed patients. Several other anti-JAK inhibitors are currently explored. This review summarises the available efficacy data from all anti-JAK inhibitors in ulcerative colitis.
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ORAL AND ENTERAL NUTRITION THERAPY IN INFLAMMATORY BOWEL DISEASES AMONG THE PEDIATRIC POPULATION: A LITERATURE REVIEW.
Souza, GN, Draghi, PF, Yonamine, GH
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2020;:e2019032
Abstract
OBJECTIVES To review the literature on oral and enteral nutrition therapy and investigate the evidence of its efficacy as a treatment, as well as in preventing relapses and reducing symptoms of inflammatory bowel diseases in the pediatric population. DATA SOURCE We performed a bibliographic search in the PubMed, Web of Science, and Latin American and Caribbean Health Sciences Literature (Literatura Latino-Americana e do Caribe em Ciências da Saúde - Lilacs) databases, using the keywords "inflammatory bowel disease," "diet," and "diet therapy" in English and Portuguese, with filters for pediatric studies published in the previous five years. DATA SUMMARY We selected 16 articles for this study, nine on exclusive and/or partial enteral nutrition and seven on modified oral diets, such as the specific carbohydrate diet (SCD) and the Crohn's Disease exclusion diet (CDED). The studies found evaluated the anthropometric profile of patients and the inflammatory profile of diseases in children before and after the introduction of each specific nutrition therapy. All interventions presented positive changes in these parameters; however, the results were inconclusive regarding the efficacy of SCD and CDED in the treatment and prevention of relapses. CONCLUSIONS Exclusive enteral nutrition has proven to be effective in inducing remission of Crohn's Disease, and the use of partial enteral nutrition for maintenance treatment has shown promising results. Other modified oral diets are inconclusive concerning their effectiveness, requiring further randomized controlled clinical trials.
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Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet?
Gkikas, K, Gerasimidis, K, Milling, S, Ijaz, UZ, Hansen, R, Russell, RK
Nutrients. 2020;(7)
Abstract
The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn's disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn's disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.
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[Time to diagnosis in paediatric inflammatory bowel disease: Key points for an early diagnosis].
Martín-de-Carpi, J, Jiménez Treviño, S, Pujol Muncunill, G, Martín-Masot, R, Navas-López, VM
Anales de pediatria. 2020;(4):242.e1-242.e9
Abstract
Paediatric inflammatory bowel disease is not very common in Spain. Its onset can be silent and an early diagnosis reduces complications and sequelae related to the disease, and can improve the prognosis. It is advisable to define the different intervals into which the time until the diagnosis is divided, as well as the peculiarities and conditions in order to be able to act on them and, to avoid, as far as possible, the diagnostic delay. The aim of this review is to provide tools to reduce the time to diagnosis.
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Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature.
Olbjørn, C, Rove, JB, Jahnsen, J
Paediatric drugs. 2020;(4):409-416
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BACKGROUND Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD. METHODS At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs. RESULTS Eight patients (four boys) aged 14-17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn's disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11-17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD. CONCLUSION In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.
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Special considerations for biologic medications in pediatric ulcerative colitis.
Jerger, L, Hyams, JS
Expert opinion on biological therapy. 2020;(4):429-435
Abstract
Introduction: More extensive disease, high rates of corticosteroid refractory and dependent disease, and the potential impact of disease on growth and development differentiate inflammatory bowel disease in children from adults. This is particularly evident in ulcerative colitis where pancolitis predominates, success of mesalamine alone in achieving remission is less than 50%, and there is a high need for immunomodulator or biologic therapies.Areas Covered: This review describes the use of infliximab, adalimumab, golimumab, and vedolizumab in the treatment of children with ulcerative colitis but is limited in scope due to the paucity of controlled clinical trials. A search of existing literature with keywords of these specific biological therapies as well as 'pediatric', 'ulcerative colitis,' and 'inflammatory bowel disease' was used to complete this review.Expert Opinion: Therapeutic drug monitoring has become standard of care when assessing dosing and changes in therapy and will play a role in future treatment planning.