Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas

Michael De Gregorio; Tanya Lee; Krupa Krishnaprasad; Gregory Amos; Yoon-Kyo An; Matthew Bastian-Jordan; Jakob Begun; Nira Borok; Dougal J M Brown; Wa Cheung; Susan J Connor; Jan Gerstenmaier; Lauren E Gilbert; Robert Gilmore; Bonita Gu; Numan Kutaiba; Allan Lee; Gillian Mahy; Ashish Srinivasan; Lena Thin; Alexander J Thompson; Christopher J Welman; Eric X Z Yong; Peter De Cruz; Daniel van Langenberg; Miles P Sparrow; Nik S Ding

doi:10.1016/j.cgh.2021.07.053

Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas

Clin Gastroenterol Hepatol. 2022 Jun;20(6):1306-1314. doi: 10.1016/j.cgh.2021.07.053. Epub 2021 Aug 11.

Authors

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

Affiliations

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.

PMID: 34389484
DOI: 10.1016/j.cgh.2021.07.053

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.

Keywords: Anti-TNF; Crohn’s Perianal Fistula; Magnetic Resonance Imaging; Therapeutic Drug Monitoring.

Publication types

Multicenter Study

MeSH terms

Adalimumab / therapeutic use
Crohn Disease* / complications
Crohn Disease* / diagnostic imaging
Crohn Disease* / drug therapy
Cross-Sectional Studies
Humans
Infliximab / therapeutic use
Rectal Fistula* / diagnostic imaging
Rectal Fistula* / drug therapy
Retrospective Studies
Treatment Outcome
Tumor Necrosis Factor Inhibitors
Tumor Necrosis Factor-alpha

Substances

Tumor Necrosis Factor Inhibitors
Tumor Necrosis Factor-alpha
Infliximab
Adalimumab