A recent study published
in JPGN Reports demonstrates how clinically meaningful questions can be addressed in Ireland with a well-organised clinical research profile and enthusiasm. Performed by Dr Niamh Ryan, a trainee in Paediatric GI as part of the group at Children’s Health Ireland (CHI), the study explores the ‘Outcomes of Tofacitinib Use in an Irish Paediatric Cohort’. UCD School of Medicine’s Clinical Professor Dr Seamus Hussey was primary supervisor for the research and Clinical Associate Professor Dr Annemarie Broderick was a collaborator for the paper.
Incidence of Inflammatory Bowel Disease (IBD) is increasing worldwide. The team in Paediatric Gastroenterology at CHI aim to investigate causes and treatments of IBD with research ethics approval, in this large group of patients to improve care. CHI at Crumlin and Tallaght is the national referral centre for Paediatric IBD, with nearly 700 children 16 years and younger attending.
One of their primary challenges in children with IBD is trying to induce clinical response/remission and prevention of treatment failure. One of the newest treatment options available in Ireland is tofacitinib, a Janus Kinase Inhibitor, licenced in Ireland for use since 2018. Tofacitinib mediates cytokine receptor signalling through STAT (signal transducer and activator of transcription) proteins which play a role in downregulating cytokine release. Limited data is available on its use and efficacy in Paediatric IBD. It is not known whether it is best used as first or second line therapy or whether it works best as monotherapy or combined with other biologic agents. The team’s paper aimed to add to this literature.
Over an almost three-year period in CHI at Crumlin, fifteen children were prescribed tofacitinib as part of their treatment regimen. Ten children were prescribed tofacitinib with another treatment agent and five as monotherapy. Two thirds of patients had a clinical response by week 16 after initiation of therapy. Tofacitinib was typically used as a later treatment option in their clinical course with mean time to therapy of 381 days (±SD 265 days) from first diagnosis of IBD.
Clinical response was assessed using a standardised clinical scoring system for Paediatric Ulcerative Colitis i.e. Paediatric Ulcerative Colitis Activity Index (PUCAI). 66 percent of children had a clinical response to tofacitinib by week 16. There was no difference in rates of remission between those who used tofacitinib on its own versus as a combined therapy with another biologic agent. If a response was achieved by week eight then a sustained response was expected by week 16 and even in cases until week 52. A failure to achieve remission by week 16 was strongly associated with progression to colectomy.
Despite having small numbers involved, this research suggests that tofacitinib could potentially be considered for use as a sole therapy. Monotherapy also poses less risk of drug-drug interaction and minimises the medicines a patient may need to take, particularly beneficial in a paediatric setting.
Congratulations to Dr Ryan and the research team.
Reference: Ryan, Niamh MB, MRCPI*; Cooper, Sarah PhD*,†; Dominik, Anna BS*,†; Quinn, Shoana MB, FRCPI*; Broderick, Annemarie MB, FRCPI*,‡; Bourke, Billy MD, FRCPI*,‡; Hussey, Séamus MB, FRCPI*,†,‡,§. Outcomes of Tofacitinib Use in an Irish Pediatric Cohort. JPGN Reports 4(3):p e332, August 2023. | DOI: 10.1097/PG9.0000000000000332
Dr Niamh Ryan graduated from University College Cork in 2015. She commenced the Paediatric BST in 2016 and Paediatric HST in 2018. She is currently finishing her final year of Paediatric Higher Specialist Training whilst working as a Paediatric Clinical Tutor with the Royal College of Surgeons Ireland. She has a special interest in Paediatric Gastroenterology.