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.
Original language | English |
---|---|
Pages (from-to) | 1306-1314 |
Number of pages | 9 |
Journal | Clinical Gastroenterology and Hepatology |
Volume | 20 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 2022 |
Keywords
- Anti-TNF
- Crohn's Perianal Fistula
- Magnetic Resonance Imaging
- Therapeutic Drug Monitoring
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}
In: Clinical Gastroenterology and Hepatology, Vol. 20, No. 6, 06.2022, p. 1306-1314.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas
AU - De Gregorio, Michael
AU - Lee, Tanya
AU - Krishnaprasad, Krupa
AU - Amos, Gregory
AU - An, Yoon-Kyo
AU - Bastian-Jordan, Matthew
AU - Begun, Jakob
AU - Borok, Nira
AU - Brown, Dougal J.M.
AU - Cheung, Wa
AU - Connor, Susan J.
AU - Gerstenmaier, Jan
AU - Gilbert, Lauren E.
AU - Gilmore, Robert
AU - Gu, Bonita
AU - Kutaiba, Numan
AU - Lee, Allan
AU - Mahy, Gillian
AU - Srinivasan, Ashish
AU - Thin, Lena
AU - Thompson, Alexander J.
AU - Welman, Christopher J.
AU - Yong, Eric X.Z.
AU - De Cruz, Peter
AU - van Langenberg, Daniel
AU - Sparrow, Miles P.
AU - Ding, Nik S.
N1 - Funding Information: Conflicts of interest The authors disclose the following: Jakob Begun has served as a speaker and a consultant for AbbVie, Celltrion, Janssen, and Pfizer. Susan J. Connor has served as a speaker and an advisory board member for AbbVie, BMS, Celgene, Celltrion, Chiesi, Ferring, Gilead, Janssen, MSD, Novartis, Pfizer, Shire, and Takeda. Unrelated to this study, Susan J. Connor has received educational grants and research support from AbbVie, Aspen, Ferring, Janssen, Pfizer, Shire, and Takeda. Peter De Cruz has served as a speaker, a consultant, and an advisory board member for AbbVie, Baxter, Ferring, Janssen, Shire, and Takeda. Nik S. Ding has served as a speaker and an advisory board member for AbbVie, BMS, Ferring, Gilead, Janssen, Pfizer, Shire, and Takeda. Miles P. Sparrow has served as a speaker and an advisory board member for AbbVie, Celgene, Emerge Health, Ferring, Janssen, MSD, Pfizer, Shire, and Takeda. Unrelated to this study, Miles P. Sparrow has received educational grants and research support from Ferring, Gilead, and Orphan. Daniel van Langenberg has served as a speaker and a consultant for AbbVie, Emerge Health, Ferring, Janssen, Pfizer, and Vifor. Unrelated to this study, Daniel van Langenberg has received educational grants and research support from Ferring, Pfizer, Shire, and Takeda. Funding Information: Michael De Gregorio (Data curation: Lead; Formal analysis: Equal; Investigation: Lead; Methodology: Equal; Project administration: Lead; Writing ? original draft: Lead; Writing ? review & editing: Lead), Tanya Lee (Conceptualization: Equal; Data curation: Equal; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Writing ? original draft: Supporting; Writing ? review & editing: Supporting), Krupa Krishnaprasad (Conceptualization: Supporting; Data curation: Equal; Project administration: Equal; Writing ? review & editing: Supporting), Gregory Amos (Data curation: Supporting; Writing ? review & editing: Supporting), Yoon-Kyo An (Data curation: Supporting; Writing ? review & editing: Supporting), Matthew Bastian-Jordan (Data curation: Supporting; Writing ? review & editing: Supporting), Jakob Begun (Data curation: Supporting; Writing ? review & editing: Supporting), Nira Borok (Data curation: Supporting; Writing ? review & editing: Supporting), Dougal J. Brown (Data curation: Supporting; Writing ? review & editing: Supporting), Wa Cheung (Data curation: Supporting; Writing ? review & editing: Supporting), Susan J. Connor (Data curation: Supporting; Writing ? review & editing: Supporting), Jan Gerstenmaier (Data curation: Supporting; Writing ? review & editing: Supporting), Lauren E Gilbert (Conceptualization: Equal; Data curation: Supporting; Methodology: Supporting; Project administration: Supporting; Writing ? review & editing: Supporting), Robert Gilmore (Data curation: Supporting; Writing ? review & editing: Supporting), Bonita Gu (Data curation: Supporting; Writing ? review & editing: Supporting), Numan Kutaiba (Data curation: Supporting; Writing ? review & editing: Supporting), Allan Lee (Data curation: Supporting; Writing ? review & editing: Supporting), Gillian Mahy (Data curation: Supporting; Writing ? review & editing: Supporting), Ashish Srinivasan (Data curation: Supporting; Writing ? review & editing: Supporting), Lena Thin (Data curation: Supporting; Writing ? review & editing: Supporting), Alexander J. Thompson (Supervision: Equal; Writing ? review & editing: Supporting), Christopher J. Welman (Data curation: Supporting; Writing ? review & editing: Supporting), Eric X. Z. Yong (Data curation: Supporting; Methodology: Supporting; Writing ? review & editing: Supporting), Peter De Cruz (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Methodology: Supporting; Writing ? original draft: Supporting; Writing ? review & editing: Equal), Daniel van Langenberg (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Lead; Methodology: Supporting; Writing ? original draft: Equal; Writing ? review & editing: Equal), Miles P. Sparrow (Conceptualization: Lead; Data curation: Supporting; Formal analysis: Equal; Investigation: Equal; Methodology: Equal; Project administration: Equal; Supervision: Equal; Writing ? original draft: Supporting; Writing ? review & editing: Equal; Co-lead senior author with Nik S Ding: Lead), Nik S. Ding (Conceptualization: Lead; Data curation: Supporting; Formal analysis: Equal; Investigation: Equal; Methodology: Equal; Project administration: Equal; Supervision: Lead; Writing ? original draft: Supporting; Writing ? review & editing: Equal; Co-lead senior author with Miles P Sparrow: Lead) Publisher Copyright: © 2021 AGA Institute
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Anti-TNF
KW - Crohn's Perianal Fistula
KW - Magnetic Resonance Imaging
KW - Therapeutic Drug Monitoring
UR - http://www.scopus.com/inward/record.url?scp=85119086822&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.07.053
DO - 10.1016/j.cgh.2021.07.053
M3 - Article
C2 - 34389484
AN - SCOPUS:85119086822
SN - 1542-3565
VL - 20
SP - 1306
EP - 1314
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 6
ER -