{
  "abstract": "Vedolizumab is an anti-integrin antibody used in the treatment of paediatric inflammatory bowel disease (PIBD). Its use is recommended in individuals with moderately to severe active disease in which treatment with a tumour necrosis factor-alpha inhibitor (antiTNF-alpha) has failed, cannot be tolerated, or is contraindicated. 1 Vedolizumab is safe and effective in PIBD. An exposure-response relationship is suggested with higher drug levels associated with improved clinical outcomes.2–4 However, this has not been replicated consistently .5 6 There is limited data on the monitoring and outcome of those on vedolizumab in contrast to those on antiTNF. Suggested levels are as follows: 37.1 mg/L at week 6, 18.4 mg/L at week 14, 12.7 mg/L during maintenance treatment.7 This study evaluates vedolizumab serum levels in PIBD patients, assessing the impact on subsequent treatment decisions and response.Patients on vedolizumab were identified from the IBD Database. Data was collected on diagnosis, age at diagnosis, previous treatment (use of biologics, azathioprine, methotrexate, anti-TNF agents, and Ustekinumab), initiation date of vedolizumab, inflammatory markers, clinical symptoms, and endoscopic findings before and after treatment. Treatment adjustments were made based on vedolizumab levels and clinical symptoms.23 children were identified, mean age at diagnosis was 9 years old (range 2- 15). 16/23 had Crohn’s (luminal), 5/23 Crohn’s with perianal disease and 2/23 Ulcerative colitis. 17/23 (73.96%) had initial treatment stepped up to biologics while 6/23 (26.09%) received biologics from diagnosis. 21/23 (91%) received antiTNF prior to switching to Vedolizumab. 2/23(8.7%) had received Ustekinumab. 19/23 (82.6%) were on Azathioprine and 10/23 (43.4%) were on Methotrexate.21/23(91.3%) had levels taken. 2/23(8.7%) had recently started and not yet had levels. 6/21(28.6%) had levels taken during induction (8 – 14 weeks),15/21 (71.4%) in maintenance (after 14 weeks). Levels in induction were (mean:15.28 mg/L, median:11.5 mg/L, range:4.5–27.9). 2/5 (40%) met therapeutic levels.1 result was still in process at time of data collection. Levels in maintenance were (mean: 17.9 mg/L, median: 8.2 mg/L, range 3.5–80.9). 5/15(33.3%) met therapeutic levels. 4/15 (26.7%) in maintenance had undetectable levels.Treatment was changed based on levels in 11/21 (52.3%), Changes done included adjusting frequency as well as dosing. In 5/21 (23.8%) vedolizumab levels > 12.7 mg/L were associated with lower inflammatory markers. 5/23 had reassessment endoscopy. 3/5 showed improved endoscopic appearances with 2/3 of these having trough levels in range.Most patients were escalated to vedolizumab following treatment with immunomodulator plus anti-TNF. While vedolizumab trough levels during induction and maintenance phase had a median of 11.5 mg/L and 8.2 mg/L respectively, no significant correlation was consistently observed between higher trough levels and reduced inflammatory markers. Standard dosing on induction and maintenance regimen was not sufficient to achieve target levels in 13/21 (61.9%). Adjustments in dosing as well as treatment intervals were made based on trough levels. Endoscopic improvement in 2/5 assessed correlated with trough levels in range, this supports a potential benefit of therapeutic drug monitoring in optimizing clinical outcomes. Further investigation is needed to determine the relationship between vedolizumab levels and clinical response in this populationReferences National Institute for Health and Care Excellence (NICE). Vedolizumab for treating moderately to severely active Crohn’s disease after prior therapy. Technology appraisal guidance [TA352]. 2015 Aug 26. Available from: https://www.nice.org.uk/guidance/ta352Ledder O, Assa A, Levine A, et al. Vedolizumab in paediatric inflammatory bowel disease: a retrospective multi-centre experience from the paediatric IBD porto group of ESPGHAN. J Crohns Colitis. 2017;11(7):897–906. doi: 10.1093/ecco-jcc/jjx082.Aardoom MA, et al. Vedolizumab trough levels in children with anti-tumor necrosis factor refractory inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2020;71(4):501–507. doi: 10.1097/mpg.0000000000002833.Plevris N, Jenkinson PW, Chuah CS, et al. Association of trough vedolizumab levels with clinical, biological, and endoscopic outcomes during maintenance therapy in inflammatory bowel disease. Frontline Gastroenterol. 2020;11(2):117–123.Hemming-Harlo M, et al. Drug levels of vedolizumab in patients with pediatric-onset inflammatory bowel disease in a real-life setting. Eur J Pediatr. 2023;183(1):313–322. doi: 10.1007/s00431-023-05255-y.Sivridaş M, Creemers RH, Wong DR, et al. Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease patients during maintenance treatment — TUMMY study. Pharmaceutics 2023;15(3):972. doi: 10.3390/pharmaceutics15030972.Jv. Exeter Clinical Laboratory International. Available from: https://www.exeterlaboratory.com/test/vedolizumab-drug-levels/",
  "authors": [
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Enenimiete Woha"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Rebecca Foulkes"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Lisa Charlton"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Zain Butt"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Virginia Chatzidaki"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Chai Lee"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Adnaan Kala"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Loveday Jago"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Maureen Lawson"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Andrew Fagbemi"
    },
    {
      "affiliations": [
        "Royal Manchester Children’s Hospital"
      ],
      "name": "Sian Copley"
    }
  ],
  "title": "OC2 Evaluation of vedolizumab levels and response to treatment adjustments in paediatric patients with inflammatory bowel disease (IBD)",
  "uid": "f1c761d1-36ba-5d49-bb51-2b5505ca08b1"
}