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; Daniël 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, Daniël W Hommes

^*Corresponding author for this work

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

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: (99m)Technetium-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 Crohńs 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 (99m)Tc-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 (99m)Tc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic (99m)Tc-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 (99m)Tc-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 (99m)Tc-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

Keywords

Adult
Animals
Annexin A5
Antibodies, Monoclonal/pharmacology
Apoptosis/drug effects
CD4-Positive T-Lymphocytes/drug effects
Colitis/chemically induced
Crohn Disease/diagnostic imaging
Disease Models, Animal
Female
Gastrointestinal Agents/pharmacology
Humans
Infliximab
Intestinal Mucosa/immunology
Male
Mice
Mice, Inbred BALB C
Mice, SCID
Middle Aged
Organotechnetium Compounds
Severity of Illness Index
Tomography, Emission-Computed, Single-Photon
Treatment Outcome
Trinitrobenzenesulfonic Acid
Tumor Necrosis Factor-alpha/antagonists & inhibitors

UN SDGs

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

Access to Document

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{b6d778aff2b7465ba9b5e2c3660b5f0c,

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: (99m)Technetium-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 Croh{\'n}s 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 (99m)Tc-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 (99m)Tc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic (99m)Tc-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 (99m)Tc-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 (99m)Tc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.",

keywords = "Adult, Animals, Annexin A5, Antibodies, Monoclonal/pharmacology, Apoptosis/drug effects, CD4-Positive T-Lymphocytes/drug effects, Colitis/chemically induced, Crohn Disease/diagnostic imaging, Disease Models, Animal, Female, Gastrointestinal Agents/pharmacology, Humans, Infliximab, Intestinal Mucosa/immunology, Male, Mice, Mice, Inbred BALB C, Mice, SCID, Middle Aged, Organotechnetium Compounds, Severity of Illness Index, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha/antagonists & inhibitors",

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}l W}",

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",

}

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, Daniël W

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: (99m)Technetium-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 Crohńs 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 (99m)Tc-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 (99m)Tc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic (99m)Tc-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 (99m)Tc-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 (99m)Tc-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: (99m)Technetium-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 Crohńs 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 (99m)Tc-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 (99m)Tc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic (99m)Tc-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 (99m)Tc-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 (99m)Tc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.

KW - Adult

KW - Animals

KW - Annexin A5

KW - Antibodies, Monoclonal/pharmacology

KW - Apoptosis/drug effects

KW - CD4-Positive T-Lymphocytes/drug effects

KW - Colitis/chemically induced

KW - Crohn Disease/diagnostic imaging

KW - Disease Models, Animal

KW - Female

KW - Gastrointestinal Agents/pharmacology

KW - Humans

KW - Infliximab

KW - Intestinal Mucosa/immunology

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, SCID

KW - Middle Aged

KW - Organotechnetium Compounds

KW - Severity of Illness Index

KW - Tomography, Emission-Computed, Single-Photon

KW - Treatment Outcome

KW - Trinitrobenzenesulfonic Acid

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors

U2 - 10.1136/gut.2006.105379

DO - 10.1136/gut.2006.105379

M3 - Article

C2 - 17082252

SN - 0017-5749

VL - 56

SP - 509

EP - 517

JO - Gut

JF - Gut

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this