Mucosal and Histologic Healing in Children With Inflammatory Bowel Disease Treated With Antitumor Necrosis Factor-Alpha

Scarallo, Luca; Alvisi, Patrizia; Bolasco, Giulia; Toma, Michele Di; Lanari, Marcello; Cangiari, Alice; Paci, Monica; Naldini, Sara; Renzo, Sara; Barp, Jacopo; Masi, Salvatore; Lionetti, Paolo

doi:10.1097/mpg.0000000000003043

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…A recent pediatric study reported histological healing in 11% of patients with Crohn's disease and 5.3% of those with UC when on adalimumab. Mucosal healing was within the same range (12%) in both disease subtypes, although the time of assessment varied from 7.6 to 18 months [28]. In adults, patients with Crohn's disease and low levels of adalimumab (<3 lg/mL) had significantly higher bowel wall thickness when measured with ultrasound, indicating poor response to therapy [29].…”

Section: Discussionmentioning

confidence: 87%

Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease

Lehtomäki

Nikkonen

Merras‐Salmio

et al. 2021

Scandinavian Journal of Gastroenterology

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Objectives: We evaluated the relationship between serum concentration and efficacy of adalimumab (ADA), an anti-tumor necrosis factor-alpha agent, in pediatric patients with inflammatory bowel disease (PIBD). Materials and methods: This retrospective cross-sectional study traced 75 patients with PIBD (Crohn's disease, n ¼ 57) treated with ADA at two tertiary centers in Finland in 2012-2018. Drug levels and drug antibody titers were chart-reviewed, and the treatment continuation rate of ADA therapy was evaluated. We also assessed the impact of trough levels in the first 3 months on the continuation of ADA within one year of therapy. Results: ADA was introduced at a median age of 13.4 years, and the median disease duration was 2.7 years. During the first year, 22 patients (29%) discontinued ADA due to either loss of response (20%, n ¼ 15) or anti-drug antibody formation (5.3%, n ¼ 4). Regarding trough levels in the first 3 months, 9/ 16 patients (56%) with trough levels <5 mg/L and 12/20 (60%) with trough levels <7.5 mg/L at 3 months discontinued the therapy by the end of the first year. In comparison, only 8/32 patients (25%) with trough levels >7.5 mg/L at 3 months discontinued treatment during the first year (p ¼ .005). At the last follow-up (median 1.5 years), 52% of the 75 patients were on maintenance therapy and had a median trough level of 8.8 mg/L. Conclusion: Higher trough levels in the first 3 months of adalimumab treatment are associated with lower rates of discontinuation due to loss of response during the first year.

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Section: Discussionmentioning

confidence: 87%

Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease

Lehtomäki

Nikkonen

Merras‐Salmio

et al. 2021

Scandinavian Journal of Gastroenterology

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“…Even when propensity score matching was performed, patients with high disease activity benefitted the most from first-line treatment in terms of clinical scores, thrombocyte counts and an increase in the albumin level. This result is promising when considering the predictive value of an early treatment response for mucosal and histological healing ( 9 ). Other studies suggest that disease severity at diagnosis is a predictor for the need for therapy escalation with TNF-a-blockers and treatment adherence to the medication before the administration of biological agents affects an escalation.…”

Section: Discussionmentioning

confidence: 91%

“…Approximately 60% respond well to anti-TNF-α treatment and 40% achieve sustained remission, according to a review of randomized controlled trials and other smaller trials ( 8 ). Scarallo and colleagues identified that biologics promote mucosal and histological healing in approximately 40% of pediatric patients with Crohn’s disease and ulcerative colitis (UC) ( 9 ). Remission at the end of induction was a predictor of long-term mucosal healing ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…Scarallo and colleagues identified that biologics promote mucosal and histological healing in approximately 40% of pediatric patients with Crohn’s disease and ulcerative colitis (UC) ( 9 ). Remission at the end of induction was a predictor of long-term mucosal healing ( 9 ). In pediatric patients with UC, treatment with IFX is independently associated with a reduced need for colectomy surgery compared to other treatment options.…”

Section: Introductionmentioning

confidence: 99%

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Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease – Data from the multicenter CEDATA-GPGE registry study

et al. 2022

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Background and aimsIn recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today.MethodsStatistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician’s Global Assessment.ResultsCrohn’s disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade.ConclusionFirst-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.

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“…In turn, corticosteroid use in pediatric patients affected by CD is associated with growth impairment and bone maturation delay [ 27 , 28 ]. Lastly, the achievement of consistent rates of deep outcomes (such as mucosal healing), along with sustained maintenance of remission, are still unfulfilled objectives [ 29 , 30 ]. Multiple studies in children with CD have demonstrated the efficacy in the induction of remission, the excellent safety profile and the nutritional benefits of exclusive enteral nutrition (EEN) [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary Management in Pediatric Patients with Crohn’s Disease

Scarallo

Lionetti

2021

Nutrients

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It has been widely endorsed that a multifactorial etiology, including interaction between genetic and environmental factors, can contribute to Crohn’s Disease (CD) pathogenesis. More specifically, diet has proven to be able to shape gut microbiota composition and thus is suspected to play a significant role in inflammatory bowel disease (IBD) pathogenesis. Moreover, poor nutritional status and growth retardation, arising from several factors such as reduced dietary intake or nutrient leakage from the gastrointestinal tract, represent the hallmarks of pediatric CD. For these reasons, multiple research lines have recently focused on the utilization of dietary therapies for the management of CD, aiming to target concurrently mucosal inflammation, intestinal dysbiosis and optimization of nutritional status. The forerunner of such interventions is represented by exclusive enteral nutrition (EEN), a robustly supported nutritional therapy; however, it is burdened by monotony and low tolerance in the long term. Novel dietary interventions, such as Crohn’s Disease Exclusion Diet or Crohn’s Disease treatment with eating, have shown their efficacy in the induction of remission in pediatric patients with CD. The aim of the present narrative review is to provide a synopsis of the available nutritional strategies in the management of pediatric CD and to discuss their application in the dietary management of these patients.

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Mucosal and Histologic Healing in Children With Inflammatory Bowel Disease Treated With Antitumor Necrosis Factor-Alpha

Cited by 7 publications

References 42 publications

Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease

Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease

Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease – Data from the multicenter CEDATA-GPGE registry study

Dietary Management in Pediatric Patients with Crohn’s Disease

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