Abstract Background On standard dosing of infliximab (IFX), one third of patients will develop secondary loss of response (LOR) by the first year and up to 50% of initial responders will develop LOR by 5 years.1 Sustained high trough levels and dose escalation are proven to increase the durability of infliximab.2 The role of proactive therapeutic drug monitoring (TDM) to guide this remains controversial. In 2019, our unit opted for proactive TDM (at week 6, week 14 and 6 monthly thereafter) as standard therapy to guide dose escalation in maintenance. We report the outcomes of our patient cohort over 2 years from initiation of IFX. Methods A retrospective chart review was performed between 01/01/2019 to 31/12/2021. All patients with IBD who received IFX were included. Patients with acute severe colitis were excluded as treatment protocol was different. Data on demographics, disease characteristics, immunomodifier, IFX dosing, frequency, drug and antibody levels were collected and analysed. Primary outcome was switching to different biologic as a marker of treatment failure. Standard IFX dosing is 5mg/kg IVI at 0, 2, 6 weeks for induction and 8 weekly in maintenance. The dose was escalated if week 6<15µg/mL, week 14/maintenance <5µg/mL, or <10µg/mL in stricturing/fistulising disease. Results 98 patients (58% male) were identified, 82% had Crohn’s disease (CD) and 18% Ulcerative Colitis (UC). Median age at diagnosis was 11 years old, and 12.5 years old at starting IFX. 81% received an immune modifier of which 64% had methotrexate and 39% azathioprine. 13% received escalated induction and 77% received escalated maintenance. The median week 6 level of standard vs escalated maintenance group was 22.8µg/mL vs 12.4µg/mL (p=0.01). 3% did not respond to induction and were discontinued. 2% developed IFX antibodies. At 1 year, 5% of CD and 22% of UC patients switched to a different biologic and at 2 years this was 13% and 44% respectively. Median time to switch was 53 weeks. Switching to alternate biologic was associated with escalated induction OR 5.2 (p<0.01) UC phenotype OR 5.6 (p<0.01) and concomitant steroid use OR 5.2 (p<0.04). Conclusion Our week 6 IFX level guided clinician decision to escalate dosing in maintenance. The outcomes for our cohort show good treatment durability particularly in CD, 95% at 1 year and 87% at 2 years, which is better than what has been reported.2 Patients with severe phenotype remain poor responders and difficult to treat as evident by receiving escalated induction, i.e escalation without TDM, and steroid use being predictors. This study adds to the growing body of evidence of the role of proactive TDM in increasing durability of IFX. References 1.Ding, N. S., Hart, A., & De Cruz, P. (2016). Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management. Alimentary pharmacology & therapeutics, 43(1), 30–51. https://doi.org/10.1111/apt.13445 2.Vahabnezhad, E., Rabizadeh, S., & Dubinsky, M. C. (2014). A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflammatory bowel diseases, 20(4), 606–613. https://doi.org/10.1097/MIB.0000000000000003

Abstract Background Subcutaneous infliximab (SC-IFX) offers comparable efficacy and safety profiles to intravenous infliximab (IV-IFX) use in patients with inflammatory bowel disease (IBD), with relative pharmacokinetic stability demonstrated 1, 2. Minimal experience with SC-IFX use in paediatric IBD has been described3, 4. We aimed to assess the clinical tolerability of SC-IFX use in children with IBD requiring anti-tumour-necrosis factor (anti-TNF) treatment. Methods A prospectively identified cohort of children with IBD commenced 120mg fortnightly SC-IFX dosing between February to July 2024 in an Australian tertiary paediatric centre. Treatment followed switch from stable intravenous infliximab (IV-IFX) biosimilar maintenance dosing, or as part of induction treatment. Baseline and four-weekly biochemical and clinical disease activity assessments were undertaken over a 12 week period of follow-up. Results Thirty-one of thirty-three patients completed the 12-week period of treatment follow-up. Median age was 15 years (IQR 14-16.5 years) and 76% (25/33) were male. Twenty-seven patients (82%) had a Crohn’s disease diagnosis. SC-IFX was prescribed as part of induction dosing in 18% (6/33). Biochemical parameters are outlined in Table 1. Median infliximab level increased by 10mg/L to 17.6mg/L at week 12, with a statistically significant increase between baseline level and all other timepoints over the follow-up period (Figure 1). Sixteen patients (48%) had a serum infliximab level greater than 20mg/L at 12 week follow-up. There was no statistically significant change in clinical disease activity indices (Paediatric Crohn’s Disease Activity Index [PCDAI] or Paediatric Ulcerative Colitis Activity Index [PUCAI]) assessed across study timepoints. No correlation between patient characteristics, including demographics, immunomodulator use and previous (if any) IV-IFX regimen, and biochemical markers at baseline or week 12 was seen. High tolerability and treatment persistence were observed in our patient group without any safety concerns. Conclusion We describe the largest cohort of children with IBD prescribed SC-IFX with short-term follow-up. Serum infliximab level increased by 10mg/L over the study period, without significant change in faecal calprotectin and clinical disease activity indices. We observed high treatment persistence in our patient group. Our real-world experience suggests paediatric SC-IFX use may be a reasonable alternative to IV-IFX dosing in children in with IBD. Further large-cohort studies and long-term paediatric data is required. References 1)Schreiber S, Ben-Horin S, Leszczyszyn J et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 2021; 160: 2340-53. 2)Buisson A, Nachury M, Bazoge M et al. Long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel disease treated with intensified doses: The REMSWITCH-LT study. Aliment Pharmacol Ther 2024; 59: 526-34. 3)Gianolio L, Armstrong K, Swann E et al. Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy. J Pediatr Gastroenterol Nutr 2023; 77: 235-9. 4)Gianolio L, Armstrong K, Swann E et al. OC5 Effectiveness and safety of switching to subcutaneous infliximab in paediatric inflammatory bowel disease patients on established intravenous biosimilar infliximab maintenance therapy: real world data from a regional cohort. Frontline Gastroenterology 2024; 15: A4-A.

Abstract Background Mental health issues such as anxiety and depression in patients with inflammatory bowel disease (IBD) are well-documented in the literature1,2. Aim: We reviewed the cohort within our new IBD psychology service, to establish the prevalence of anxiety and depression in the Australian paediatric setting. Methods 213 outpatients aged 5-18 attending the outpatient IBD service at the Children’s Hospital at Westmead, Australia were recruited from April to October 2024. They completed a validated self-report tool, PROMIS Paediatric Profile v2.0 – Profile 25, which measures anxiety, depression, mobility, fatigue, peer relationships, pain interference, and pain intensity. Clinical disease data, including PUCAI/PCDAI scores and biochemical markers (faecal calprotectin, ESR, and CRP) were collected for the same visits. Demographic data included age, sex, disease type (Crohn’s Disease or Ulcerative Colitis), and age at diagnosis. Results Moderate to severe levels of anxiety, depression, and fatigue were reported by 28.7%, 20.2%, and 26.7% of participants, respectively. There was a significant difference in psychological distress (combined anxiety and depression) across different groups when stratified on age of diagnosis (i.e. ages 0-5, 6-12, and 13-18; F(2, 208)=5.37, p=.005). Psychological distress positively correlated with clinical disease severity (PCDAI: r=.244, p=.007; PUCAI: r=.317, p=.004), and pain interference (r=.600, p<.001) and intensity (r=.461, p<.001); negatively correlated with mobility (r=-.514, p<.001) and peer relationships (r=-.437, p<.001). A hierarchical regression was conducted to assess predictors of psychological distress among participants. Fatigue emerged as the strongest predictor in the final model, significantly explaining additional variance in distress levels (F(1, 164)=79.34, p<.001). Additionally, mobility and sex also emerged as significant predictors of psychological distress (ps=.049 and .017, respectively), while age, biochemical markers, and disease severity were non-significant. This model explained 57.3% of the variance in psychological distress. Conclusion Paediatric patients with IBD experience significant burden from anxiety, depression, and fatigue. The strong association between fatigue and psychological distress mirrors findings in the adult IBD population3, suggesting that fatigue and psychological factors significantly influence each other, independent of the disease state. These results underscore the importance of targeted screening and management of psychological symptoms to improve IBD care and improve quality of life in paediatric patients. References 1.Butwicka A, Olén O, Larsson H, et al. Association of childhood-onset inflammatory bowel disease with risk of psychiatric disorders and suicide attempt. JAMA Pediatr. 2019 Oct;173(10):969-978. doi: 10.1001/jamapediatrics.2019.2662. 2.Cooney R, Tang D, Barrett K, Russell RK. Children and young adults with inflammatory bowel disease have an increased incidence and risk of developing mental health conditions: a UK population-based cohort study. Inflamm Bowel Dis. 2024 Aug;30(8):1264-1273. doi: 10.1093/ibd/izad169. 3.Uhlir V, Stallmach A, Grunert PC. Fatigue in patients with inflammatory bowel disease-strongly influenced by depression and not identifiable through laboratory testing: a cross-sectional survey study. BMC Gastroenterol. 2023 Aug 22;23(1):288. doi: 10.1186/s12876-023-02906-0. PMID: 37608313; PMCID: PMC10463723.

Earlier introduction of infliximab (IFX) in Crohn’s disease (CD) may be associated with a sustained remission.

Journal of Gastroenterology and HepatologyVolume 31, Issue 9 p. 1512-1512 Education and Imaging Gastrointestinal: Unusual presentation of duodenal web in an infant K Thacker, K Thacker Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this authorG Jevon, G Jevon Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this authorE Whan, E Whan Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this author K Thacker, K Thacker Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this authorG Jevon, G Jevon Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this authorE Whan, E Whan Princess Margaret Hospital for Children, Perth, AustraliaSearch for more papers by this author First published: 05 April 2016 https://doi.org/10.1111/jgh.13406Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume31, Issue9September 2016Pages 1512-1512 RelatedInformation