Michael De Gregorio1, Tanya Lee2, Krupa Krishnaprasad3, Gregory Amos4, Yoon-Kyo An5, Matthew Bastian-Jordan4, Jakob Begun6, Nira Borok7, Dougal J M Brown8, Wa Cheung9, Susan J Connor10, Jan Gerstenmaier9, Lauren E Gilbert11, Robert Gilmore12, Bonita Gu13, Numan Kutaiba14, Allan Lee15, Gillian Mahy16, Ashish Srinivasan17, Lena Thin18, Alexander J Thompson19, Christopher J Welman20, Eric X Z Yong21, Peter De Cruz22, Daniel van Langenberg23, Miles P Sparrow24, Nik S Ding19. 1. St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia; University of Melbourne, Medicine, Parkville, Australia. Electronic address: michael.degregorio@svha.org.au. 2. St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia. 3. St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia; QIMR Berghofer Medical Research Institute, Gut Health Lab, Brisbane, Australia. 4. University of Queensland, Medicine, St Lucia, Australia; Queensland X-ray, Medical Imaging, Brisbane, Australia. 5. University of Queensland, Medicine, St Lucia, Australia; Mater Hospital Brisbane, Gastroenterology, South Brisbane, Australia. 6. Mater Hospital Brisbane, Gastroenterology, South Brisbane, Australia; University of Queensland, Mater Research Institute, St Lucia, Australia. 7. Liverpool Hospital, Medical Imaging, Liverpool, Australia; South Western Sydney Local Health District, Medicine, Liverpool, Australia. 8. Townsville University Hospital, Medical Imaging, Douglas, Australia. 9. Alfred Health, Medical Imaging, Melbourne, Australia. 10. Liverpool Hospital, Gastroenterology and Hepatology, Liverpool, Australia; Ingham Institute for Applied Medical Research, Medicine, Liverpool, Australia; University of New South Wales, South Western Sydney Clinical School, Sydney, Australia. 11. Alfred Health, Gastroenterology, Melbourne, Australia. 12. Austin Health, Gastroenterology, Heidelberg, Australia. 13. Liverpool Hospital, Gastroenterology and Hepatology, Liverpool, Australia; University of New South Wales, South Western Sydney Clinical School, Sydney, Australia; Royal Prince Alfred Hospital, Gastroenterology and Hepatology, Camperdown, Australia. 14. Austin Health, Radiology, Heidelberg, Australia; Eastern Health, Radiology, Box Hill, Australia. 15. Imaging Associates Eastern Health, Medical Imaging, Melbourne, Australia; Peter MacCallum Cancer Centre, Cancer Imaging, Melbourne, Australia. 16. Townsville University Hospital, Gastroenterology, Douglas, Australia. 17. Austin Health, Gastroenterology, Heidelberg, Australia; Eastern Health, Gastroenterology, Box Hill, Australia; Monash University, Medicine, Clayton, Australia. 18. Fiona Stanley Hospital, Gastroenterology, Murdoch, Australia; University of Western Australia, School of Medicine and Pharmacology, Crawley, Australia. 19. St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia; University of Melbourne, Medicine, Parkville, Australia. 20. Fiona Stanley Hospital, Medical Imaging, Murdoch, Australia. 21. St Vincent's Hospital Melbourne, Medical Imaging, Fitzroy, Australia. 22. University of Melbourne, Medicine, Parkville, Australia; Austin Health, Gastroenterology, Heidelberg, Australia. 23. Eastern Health, Gastroenterology, Box Hill, Australia; Monash University, Medicine, Clayton, Australia. 24. Alfred Health, Gastroenterology, Melbourne, Australia; Monash University, Medicine, Clayton, Australia.
Abstract
BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 μg/mL; adalimumab 9.1 vs 6.2 μg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 μg/mL; P < .05; adalimumab 9.8 vs 6.2 μg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.
BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 μg/mL; adalimumab 9.1 vs 6.2 μg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 μg/mL; P < .05; adalimumab 9.8 vs 6.2 μg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.