c419084fa1b2fd6bdbf2a4f9f281b352 pmc_11678755.pdf 49022628a9540ea34b9ed1c09ceeaca81960fb33 pmc_11678755.pdf 8c1051023c19edab9f3492b579792e9b0e879eed669e05bcde7652f0fdde207b pmc_11678755.pdf Title: Long-Term Effectiveness and Safety of Proactive Therapeutic Drug Monitoring of Infliximab in Paediatric Inflammatory Bowel Disease: A Real-World Study Subject: Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations 5 g/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) g/mL (reactive) and 12.38 (9.24) g/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients. Keywords: therapeutic drug monitoring; infliximab; inflammatory bowel diseases; children Author: Susana Clemente Bautista, Óscar Segarra Cantón, Núria Padullés-Zamora, Sonia García García, Marina Álvarez Beltrán, María Larrosa García, Maria Josep Cabañas Poy, Maria Teresa Sanz-Martínez, Ana Vázquez, Maria Queralt Gorgas Torner and Marta Miarons Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Dec 12 02:22:01 2024 CET ModDate: Thu Dec 12 02:42:41 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1691092 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QMCQLP+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YSCNED+EURM10 Type 1 Builtin yes yes yes 16 0 QBADDD+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 UMUTZF+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 BZARAF+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 RWBCRL+CMSY10 Type 1 Builtin yes yes yes 37 0 ODUQCM+VnURWPalladioL Type 1 Custom yes yes yes 42 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 80 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 84 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 88 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 92 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 109 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 134 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 138 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 142 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 146 0 Arial,Bold TrueType WinAnsi no no no 154 0 BCDKEE+CALIBRI TrueType WinAnsi yes yes no 157 0 BCDLEE+CALIBRI,Bold TrueType WinAnsi yes yes no 161 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 177 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 181 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 185 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 189 0 BCDJEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 196 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 209 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 213 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 217 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 221 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-08 02:53:07 CET RepresentationInformation: pmc_11678755.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-06 02:51:29 CET Size: 1691092 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 495 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Material and Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Serum Samples and Data Collection Destination: subsection.2.2 Item: Title: Laboratory Tests Destination: subsection.2.3 Item: Title: Therapeutic Drug Monitoring and Samples Destination: subsection.2.4 Item: Title: Predictions to Individualise Dosing Destination: subsection.2.5 Item: Title: Therapeutic Outcomes Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Patient Characteristics Destination: subsection.3.1 Item: Title: Administrations, Trough Concentrations, and Antibodies to IFX Destination: subsection.3.2 Item: Title: Treatment Intervention Destination: subsection.3.3 Item: Title: Efficacy Destination: subsection.3.4 Children: Item: Title: Treatment Failures and Loss of Response Destination: subsubsection.3.4.1 Item: Title: Clinical, Biological, and Endoscopic Remission Destination: subsubsection.3.4.2 Item: Title: Hospitalisations and Emergency Visits Destination: subsubsection.3.4.3 Item: Title: Safety Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Long-Term Effectiveness and Safety of Proactive Therapeutic Drug Monitoring of Infliximab in Paediatric Inflammatory Bowel Disease: A Real-World Study Author: Susana Clemente Bautista, Óscar Segarra Cantón, Núria Padullés-Zamora, Sonia García García, Marina Álvarez Beltrán, María Larrosa García, Maria Josep Cabañas Poy, Maria Teresa Sanz-Martínez, Ana Vázquez, Maria Queralt Gorgas Torner and Marta Miarons Subject: Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations 5 g/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) g/mL (reactive) and 12.38 (9.24) g/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients. 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