{
  "abstract": "Ustekinumab, a monoclonal antibody to interleukins (IL) 12 and 23, is proven to be effective in induction and maintenance of remission in both adult and paediatric inflammatory bowel disease (PIBD), although it remains unlicensed for the paediatric population. Anti-tumour necrosis factor (TNF) (infliximab and adalimumab) are recommended as first line biologics in PIBD, but are associated with primary non-response rates of around 30% with further patients experiencing secondary loss of response over time. 1 Multicentre studies have shown remission rates of 50%, 59.6% and 63.8% at 16, 26 and 52 weeks respectively in ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU)1 and 41.2% at week 48 in Crohn’s disease (CD).2 Standard dosing involves an initial weight based IV dose followed by weight based subcutaneous dose at 8 weeks then 12 weekly thereafter. There is limited data on therapeutic level targets and antibody formation and variable access between centres to this monitoring.We aimed to evaluate the outcomes of patients treated with ustekinumab in our tertiary centre.11 patients receiving ustekinumab were identified from the departmental database and electronic records were retrospectively reviewed. Data was collected on diagnosis, age at diagnosis, disease location, perianal disease, previous treatment with biologics or immunomodulators, reason for switching to ustekinumab, response to ustekinumab, need for any dose modification or switch to an alternative biologic.Age ranged from 3 – 14 years. All patients had Crohn’s disease. 7/11 (64%) had ileocolonic disease, 3/11 (27%) colonic and 1/11 (9%) upper gastrointestinal and ileocolonic disease. 7/11 (64%) had perianal disease. Ustekinumab was the 2nd biologic for 3/11 (27%), 3rd for 7/11 (64%), 4th for 1/11 (9%). Of those receiving ustekinumab as 3rd line biologic, 6/7 (86%) switched from one anti-TNF to the other before switching to ustekinumab, 1/7 switched from infliximab to vedolizumab then to ustekinumab. The patient receiving ustekinumab as 4th line had received infliximab, adalimumab and vedolizumab prior to switching to ustekinumab.Reasons for switching to ustekinumab were recorded as primary non-response to 2 anti-TNF agents (1/11), primary non-response to 2 anti-TNF agents and vedolizumab (1/11), secondary loss of response to anti-TNF (4/11), secondary loss of response to anti-TNF then vedolizumab (1/11), antibody formation to anti-TNF (3/11), and 1/11 did not have rationale for switching clearly documented.7/11 (64%) had documented clinical response or remission after switching to ustekinumab. 2 patients not responding subsequently switched from ustekinumab to vedolizumab. 1 patient underwent surgery due to failing medical management. 1 patient required dose optimisation based on symptoms. Measurement of levels and antibodies were not available during the period of this study. There were no adverse events reported.In conclusion, ustekinumab is a safe and effective therapy in paediatric Crohn’s disease with response rates in line with published literature. Response may be seen after failure of 2 or more alternative biologics. Large scale multicentre studies to establish therapeutic levels and access to level and antibody measurement may assist with dose optimisation and prevent treatment failure.References Cohen S, Rolandsdotter H, Kolho KL, Turner D, Tzivinikos C, Bramuzzo M, Pujol-Muncunill G, Scarallo L, Urlep D, Rinawi F, Granot M, Kang B, Longueville Y, Rodríguez-Belvís MV, Weintraub Y, Navas-López VM, Yerushalmy-Feler A. Effectiveness and safety of ustekinumab in pediatric ulcerative colitis: a multi-center retrospective study from the pediatric IBD porto group of ESPGHAN. Paediatr Drugs 2024 Sep;26(5):609–617. doi: 10.1007/s40272-024-00631-z. Epub 2024 May 23. PMID: 38780740; PMCID: PMC11335845.Turner D, Rosh JR, Cohen SA, Griffiths AM, Hyams JS, Kierkuś J, Adedokun OJ, Strauss R, Kim L, Volger S; UniStar Study Group. Ustekinumab in paediatric patients with moderately to severely active Crohn’s disease: uniStar study long-term extension results. J Pediatr Gastroenterol Nutr. 2024 Aug;79(2):315–324. doi: 10.1002/jpn3.12252. Epub 2024 May 27. PMID: 38801079.",
  "authors": [
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Maham Zeba"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Rose Alhaleem"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Rebecca Foulkes"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Lisa Charlton"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Virginia Chatzidaki"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Chai Leng Lee"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Adnaan Kala"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Loveday Jago"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Andrew Fagbemi"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Maureen Lawson"
    },
    {
      "affiliations": [
        "Royal Manchester Children Hospital"
      ],
      "name": "Sian Copley"
    }
  ],
  "title": "OC44 Ustekinumab in paediatric inflammatory bowel disease: a single tertiary centre experience",
  "uid": "fa0a1525-4428-57e1-9dce-1ff298829337"
}