Infliximab, Immunomodulators and Treatment Failures in Paediatric and Adolescent Patients with Crohn’s Disease: a Nationwide Cohort Study

Abstract Background and Aims In paediatric patients with Crohn’s disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months. Design Using Danish registries, we identified patients with Crohn’s disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015. Results We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32–0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45–0.97] in patients receiving combination therapy. Conclusions The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.

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Mo1900 Combination Therapy With Infliximab and Methotrexate Does Not Improve Crohn's Disease Outcome and Infliximab Tolerance Compared to Infliximab Therapy Alone

Gastroenterology ◽

10.1016/s0016-5085(16)32742-1 ◽

2016 ◽

Vol 150 (4) ◽

pp. S811

Author(s):

Guillaume Pineton de chambrun ◽

Louise Libier ◽

Michael Collins ◽

Maria Nachury ◽

Corinne Gower-Rousseau ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Infliximab Therapy ◽

Disease Outcome

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DOP055. Combination therapy with infliximab and azathioprine improves Crohn's disease outcome and infliximab tolerance compared to infliximab therapy alone

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jju027.083 ◽

2015 ◽

Vol 9 (suppl 1) ◽

pp. S56-S56

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Infliximab Therapy ◽

Disease Outcome

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CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn’s disease

Scientific Reports ◽

10.1038/s41598-020-80663-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yulan Ye ◽

Liping Zhang ◽

Tong Hu ◽

Juan Yin ◽

Lijuan Xu ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Cell Apoptosis ◽

Mononuclear Cells ◽

Circular Rnas ◽

Infliximab Treatment ◽

Peripheral Blood Mononuclear ◽

Novel Approach ◽

Tnf Α

AbstractIncreasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn’s disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.

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Tu1341 Combination Therapy With Infliximab and Azathioprine Improves Crohn's Disease Outcome and Infliximab Tolerance Compared to Infliximab Therapy Alone

Gastroenterology ◽

10.1016/s0016-5085(15)32928-0 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-864

Author(s):

Guillaume Pineton de Chambrun ◽

Louise Libier ◽

Michael Collins ◽

Maria Nachury ◽

Dine Koriche ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Infliximab Therapy ◽

Disease Outcome

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Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol

BMJ Open ◽

10.1136/bmjopen-2020-043921 ◽

2021 ◽

Vol 11 (7) ◽

pp. e043921

Author(s):

Bonita Gu ◽

Michael De Gregorio ◽

Joseph Louis Pipicella ◽

Niels Vande Casteele ◽

Jane M Andrews ◽

...

Keyword(s):

Crohn’S Disease ◽

Randomised Controlled Trial ◽

Crohn's Disease ◽

Controlled Trial ◽

Dropout Rate ◽

Infliximab Therapy ◽

Infliximab Treatment ◽

Patient Reported ◽

Fistula Healing ◽

Randomised Controlled

IntroductionPerianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.Methods and analysisPatients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.Ethics and disseminationResults will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

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Infliximab for Anoperineal Lesions in Crohn's Disease: Remission Appears to be Based on Rapid Combination Therapy at High Doses

Journal of Coloproctology ◽

10.1055/s-0041-1739549 ◽

2021 ◽

Author(s):

Nadia Fathallah ◽

Cosmin Cristea ◽

Hélène Beaussier ◽

Sonia Khirani ◽

Vincent de Parades

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Real Life ◽

Treatment Compliance ◽

Infliximab Treatment ◽

Combination Treatments ◽

Poor Treatment ◽

Anoperineal Lesions ◽

High Doses

Abstract Study Aim The aim of the present study was to compare in real life the characteristics of treatment with infliximab according to the presence or absence of anoperineal involvement in Crohn's disease. Methods We performed a single-center, prospective, non-interventional study, on patients with Crohn's disease in remission who had been treated with infliximab for at least 1 year. Patients with poor treatment compliance, on antibiotics, or those with a stoma were excluded. Results We included 52 patients in this study: 34 with anoperineal lesions with or without luminal lesions, and 18 with luminal lesions only. Patients with anoperineal lesions were more likely to have undergone surgery (70.6% versus 38.9%, p = 0.027), had a shorter median time to infliximab treatment initiation (0.5 versus 5.5 years, p = 0.005), a higher mean dose of infliximab (6.6 versus 5.1 mg/kg, p = 0.015), and were more likely to receive combination treatments including infliximab (52.9% versus 11.1%, p = 0.008) than patients with luminal involvement only. Conclusions In our study, infliximab treatment was initiated more quickly, at higher doses, and more in combination therapy for anoperineal Crohn's disease than for luminal damage alone. Additional studies are required to confirm this finding and to assess the tolerance of this treatment throughout patient management.

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Improvement of Lumbar Bone Mass after Infliximab Therapy in Crohn’s Disease Patients

Canadian Journal of Gastroenterology ◽

10.1155/2007/216162 ◽

2007 ◽

Vol 21 (10) ◽

pp. 637-642 ◽

Cited By ~ 32

Author(s):

Marina Mauro ◽

Vladimir Radovic ◽

David Armstrong

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Bone Mass ◽

Disease Activity ◽

Bone Mineral ◽

Infliximab Therapy ◽

Control Group ◽

Infliximab Treatment ◽

Mineral Density ◽

Bone Mass Loss

BACKGROUND: Patients with Crohn’s disease (CD) have a high risk of developing osteoporosis, but the mechanisms underlying bone mass loss are unclear. Elevated proinflammatory cytokines, such as tumour necrosis factor-alpha (TNFα), have been implicated in the pathogenesis of bone resorption.AIM: To assess whether suppression of TNFα with infliximab treatment has a beneficial effect on lumbar bone mass.METHODS: Adult CD patients who had received infliximab treatment, and who underwent lumbar densitometric evaluation before and during treatment, were selected. Adult CD patients who had never received infliximab treatment were selected as controls. Information regarding age, sex, weight, duration of CD, use of glucocorticoids and bisphosphonates, and signs of disease activity between both densitometric measurements were collected.RESULTS: Data from 45 patients were analyzed. The control group (n=30, mean [± SD] 26.7±9 years of age) had a significantly higher increase in body weight between both evaluations (6.26%±8%) than the infliximab group (n=15, 30.6±13 years), which had an increase of 0.3%±7.4%. There was a strong correlation between the final weight and lumbar bone mineral content (BMC) in both groups. The infliximab group had a significant increase in lumbar bone area (4.15%±6.6%), BMC (12.8%±13.6%) and bone mineral density (8.13%±7.7%) between both evaluations (interval 22.6±11 months) compared with the control group. The increase in BMC in patients who had received infliximab treatment was significant when compared with control patients who had received glucocorticoids (n=8) or had evidence of disease activity (n=13).CONCLUSION: Infliximab therapy improved lumbar bone mass independent of nutritional status. This finding suggests that TNFα plays a role in bone loss in CD.

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