Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease

Jan M.H. Van Den Brande; Tamara C. Koehler; Zuzana Zelinkova; Roelof J. Bennink; Anje A. Te Velde; Fibo J.W. Ten Cate; Sander J.H. Van Deventer; Maikel P. Peppelenbosch; Daniët W. Hommes

doi:10.1136/gut.2006.105379

Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease

Jan M.H. Van Den Brande^*
, Tamara C. Koehler
, Zuzana Zelinkova
, Roelof J. Bennink
, Anje A. Te Velde
, Fibo J.W. Ten Cate
, Sander J.H. Van Deventer
, Maikel P. Peppelenbosch
, Daniët W. Hommes

^*Corresponding author for this work

University of Amsterdam
University of Groningen

Research output: Contribution to journal › Article › Academic › peer-review

166 Citations (Scopus)

Abstract

Background:

The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro.

Aim:

To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease.

Methods:

^99mTechnetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points).

Results:

Colonic uptake of ^99mTc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of ^99mTc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic ^99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41 (0.07) (p<0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of ^99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI > 100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.

Conclusions:

These in vivo observations support the notion that colonic uptake of ^99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.

Original language	English
Pages (from-to)	509-517
Number of pages	9
Journal	Gut
Volume	56
Issue number	4
DOIs	https://doi.org/10.1136/gut.2006.105379
Publication status	Published - Apr 2007
Externally published	Yes

Bibliographical note

Funding Information:
The authors would like to thank Dr. Rachel McKendry (Department of Chemistry, Cambridge University) for providing the PEO-thiol, Kat Gaus and Dr. Lisa Hall (Institute of Biotechnology, Cambridge University) for the SPR measurements with LDL and oxLDL, and for helpful discussions. A.M.M. is grateful to Unilever Ltd. for financial support.

MPP is supported by the Dutch Digestive Disease Foundation.
DWH is a clinical fellow of the Netherlands Organisation for Health
Research and Development.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1136/gut.2006.105379

Cite this

Van Den Brande, J. M. H., Koehler, T. C., Zelinkova, Z., Bennink, R. J., Te Velde, A. A., Ten Cate, F. J. W., Van Deventer, S. J. H., Peppelenbosch, M. P., & Hommes, D. W. (2007). Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease. Gut, 56(4), 509-517. https://doi.org/10.1136/gut.2006.105379

@article{25ce13b1d10b4fd28c0705925b5c2392,

title = "Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease",

abstract = "Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro. Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease. Methods: 99mTechnetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points). Results: Colonic uptake of 99mTc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of 99mTc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic 99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41 (0.07) (p<0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7\% in colonic uptake of 99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI > 100 points at week 2) compared with 15.2\% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.Conclusions: These in vivo observations support the notion that colonic uptake of 99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.",

author = "\{Van Den Brande\}, \{Jan M.H.\} and Koehler, \{Tamara C.\} and Zuzana Zelinkova and Bennink, \{Roelof J.\} and \{Te Velde\}, \{Anje A.\} and \{Ten Cate\}, \{Fibo J.W.\} and \{Van Deventer\}, \{Sander J.H.\} and Peppelenbosch, \{Maikel P.\} and Hommes, \{Dani{\"e}t W.\}",

note = "Funding Information: The authors would like to thank Dr. Rachel McKendry (Department of Chemistry, Cambridge University) for providing the PEO-thiol, Kat Gaus and Dr. Lisa Hall (Institute of Biotechnology, Cambridge University) for the SPR measurements with LDL and oxLDL, and for helpful discussions. A.M.M. is grateful to Unilever Ltd. for financial support. MPP is supported by the Dutch Digestive Disease Foundation. DWH is a clinical fellow of the Netherlands Organisation for Health Research and Development.",

year = "2007",

month = apr,

doi = "10.1136/gut.2006.105379",

language = "English",

volume = "56",

pages = "509--517",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "4",

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TY - JOUR

T1 - Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease

AU - Van Den Brande, Jan M.H.

AU - Koehler, Tamara C.

AU - Zelinkova, Zuzana

AU - Bennink, Roelof J.

AU - Te Velde, Anje A.

AU - Ten Cate, Fibo J.W.

AU - Van Deventer, Sander J.H.

AU - Peppelenbosch, Maikel P.

AU - Hommes, Daniët W.

N1 - Funding Information: The authors would like to thank Dr. Rachel McKendry (Department of Chemistry, Cambridge University) for providing the PEO-thiol, Kat Gaus and Dr. Lisa Hall (Institute of Biotechnology, Cambridge University) for the SPR measurements with LDL and oxLDL, and for helpful discussions. A.M.M. is grateful to Unilever Ltd. for financial support. MPP is supported by the Dutch Digestive Disease Foundation. DWH is a clinical fellow of the Netherlands Organisation for Health Research and Development.

PY - 2007/4

Y1 - 2007/4

N2 - Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro. Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease. Methods: 99mTechnetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points). Results: Colonic uptake of 99mTc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of 99mTc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic 99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41 (0.07) (p<0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of 99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI > 100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.Conclusions: These in vivo observations support the notion that colonic uptake of 99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.

AB - Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro. Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease. Methods: 99mTechnetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points). Results: Colonic uptake of 99mTc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of 99mTc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic 99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41 (0.07) (p<0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of 99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI > 100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.Conclusions: These in vivo observations support the notion that colonic uptake of 99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.

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U2 - 10.1136/gut.2006.105379

DO - 10.1136/gut.2006.105379

M3 - Article

C2 - 17082252

AN - SCOPUS:34147211616

SN - 0017-5749

VL - 56

SP - 509

EP - 517

JO - Gut

JF - Gut

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ER -

Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease

Abstract

Bibliographical note

UN SDGs

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