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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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Abstract
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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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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Pouchitis: Treatment dilemmas at different stages of the disease.
Barreiro-de Acosta, M, Bastón-Rey, I, Calviño-Suárez, C, Enrique Domínguez-Muñoz, J
United European gastroenterology journal. 2020;(3):256-262
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Abstract
Pouchitis is a frequent complication in ulcerative colitis patients after proctocolectomy with ileal pouch-anal anastomosis. It is an unspecific inflammation of the pouch with unknown aetiology. First-line treatment for acute and chronic pouchitis is antibiotics. Some cases of severe chronic refractory pouchitis may benefit from biological treatment. Anti-tumour necrosis factor should be recommended as the first option, leaving the new biologicals for multirefractory patients. Permanent ileostomy may be an option in severe cases, after failure of medical treatment. Prophylaxis therapy with a probiotic mixture is recommended after the first episode of pouchitis, whereas it is not clear whether probiotics are useful for all patients after surgery. Here, we present a case report and review the treatment options in different forms of pouchitis.
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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.
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Cannabis for the Treatment of Crohn's Disease and Ulcerative Colitis: Evidence From Cochrane Reviews.
Kafil, TS, Nguyen, TM, MacDonald, JK, Chande, N
Inflammatory bowel diseases. 2020;(4):502-509
Abstract
BACKGROUND We systematically reviewed the safety and effectiveness of cannabis and cannabinoids treatment for Crohn's disease (CD) and ulcerative colitis (UC). METHODS MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register were searched for relevant studies. MAIN RESULTS Five randomized controlled trials (3 CD and 2 UC studies, 185 participants) were included. One CD study (N = 21) showed 45% (5 of 11) of the cannabis cigarette group experienced clinical remission compared with 10% (1 of 10) of the placebo group (risk ratio [RR] 4.55; 95% CI, 0.63-32.56). Another CD study (N = 19) did not show significant rates of clinical remission. Forty percent (4 of 10) of participants in the cannabis oil group experienced remission compared with 33% (3 of 9) of the placebo group (RR 1.20; 95% CI, 0.36-3.97). A UC study (N = 60) did not have significant clinical remission rates. Twenty-four percent (7 of 29) of cannabis oil participants experienced remission compared with 26% (8 of 31) of placebo participants (RR 0.94; 95% CI, 0.39-2.25). A second UC study (N = 32) showed the effects on disease activity, C-reactive protein levels, and fecal calprotectin levels were uncertain. Adverse events were more prevalent in the cannabis groups for both CD and UC studies. GRADE analysis for the UC and CD studies ranged from very low to moderate. CONCLUSIONS In summary, no firm conclusions can be made regarding the safety and effectiveness of cannabis and cannabinoids in adults with CD and UC.
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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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The Rundown of Dietary Supplements and Their Effects on Inflammatory Bowel Disease-A Review.
Malinowski, B, Wiciński, M, Sokołowska, MM, Hill, NA, Szambelan, M
Nutrients. 2020;(5)
Abstract
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are a life-long, chronic, and relapsing problem affecting 11.2 million people worldwide. To date, there is pharmacological therapy to treat symptoms such as diarrhea, constipation, and abdominal cramping/pain. These medications also help to alleviate everyday discomfort; however, there are no curative therapies. Recent studies have investigated the combination of pharmacological treatment along with nutritional interventions to improve quality of life and risk of disease relapse. Dietary supplements, specifically probiotics, polyphenols, fibers, fatty acids and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diets (FODMAP diets), have been closely looked at to determine their effect, if any, on the development of inflammatory bowel disease and its course of progression. Approximately 30 studies were carefully reviewed and analyzed to appreciate the value of these above-mentioned supplements and their influence on this gastrointestinal disease. After analysis, it has been demonstrated that by implementing fibers, polyphenols, and fatty acids, as well as keeping a low-saccharide diet for those patients with Crohn's disease and ulcerative colitis can improve quality of life and invoke clinical remission. Some polyphenols, specifically curcumin and resveratrol, have proved to decrease disease activity in studies reviewed. Although these studies have become a topic of recent interest, it would be of great value to doctors and patients alike, to continue in this direction of research and to improve the findings for best treatment substances and dosages. This would lead to increased quality of life and disease control leading to fewer complications in the future.
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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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Abstract
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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[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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JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications.
Agrawal, M, Kim, ES, Colombel, JF
Journal of Crohn's & colitis. 2020;(Supplement_2):S755-S760
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Abstract
Janus kinase inhibitors [JAKi] are a new class of small molecule drugs that modulate inflammatory pathways by blocking one or more JAK receptors, and are increasingly being used in the treatment of immune-mediated diseases. Tofacitinib, a non-selective JAKi, is now approved for moderate-to-severe ulcerative colitis [UC] that is refractory or intolerant to tumour necrosis factor inhibitors [TNFi]. Whereas tofacitinib is associated with the advantages of oral administration, rapid onset of action, and lack of immunogenicity over TNFi, there are many safety considerations to take into account such as the risk of thromboembolism, infections, and hyperlipidaemia: each with specific nuances pertaining to prevention and monitoring strategies. Considerations such as pregnancy, breastfeeding, and history of malignancy also are to be navigated with utmost caution, given that very few data are available for guidance. With the use of JAKi in the real world progressively over time, safety implications will become more lucid, including caveats pertaining to JAK selectivity and gut-selective JAKi, as well as mechanistic data pertaining to adverse effects. This Viewpoint serves as a practical guide for clinicians managing inflammatory bowel disease [IBD] patients to navigate safety concerns around JAKi, including preventive and monitoring strategies.