First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy.
Identifieur interne : 000624 ( 2020/Analysis ); précédent : 000623; suivant : 000625First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy.
Auteurs : Raja Atreya [Allemagne] ; Ulrike Billmeier [Allemagne] ; Timo Rath [Allemagne] ; Jonas Mudter [Allemagne] ; Michael Vieth [Allemagne] ; Helmut Neumann [Allemagne] ; Markus F. Neurath [Allemagne]Source :
- World journal of gastroenterology [ 2219-2840 ] ; 2015.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Agents gastro-intestinaux (administration et posologie), Agents gastro-intestinaux (effets indésirables), Anti-inflammatoires (administration et posologie), Anti-inflammatoires (effets indésirables), Anticorps monoclonaux humanisés (administration et posologie), Anticorps monoclonaux humanisés (effets indésirables), Biopsie, Coloscopie, Cytokines (génétique), Cytokines (immunologie), Femelle, Humains, Rectocolite hémorragique (diagnostic), Rectocolite hémorragique (génétique), Rectocolite hémorragique (immunologie), Rectocolite hémorragique (traitement médicamenteux), Récepteurs à l'interleukine-6 (antagonistes et inhibiteurs), Récepteurs à l'interleukine-6 (immunologie), Résultat thérapeutique, Thérapie moléculaire ciblée, Évolution de la maladie.
- MESH :
- administration et posologie : Agents gastro-intestinaux, Anti-inflammatoires, Anticorps monoclonaux humanisés.
- antagonistes et inhibiteurs : Récepteurs à l'interleukine-6.
- diagnostic : Rectocolite hémorragique.
- effets indésirables : Agents gastro-intestinaux, Anti-inflammatoires, Anticorps monoclonaux humanisés.
- génétique : Cytokines, Rectocolite hémorragique.
- immunologie : Cytokines, Rectocolite hémorragique, Récepteurs à l'interleukine-6.
- traitement médicamenteux : Rectocolite hémorragique.
- Adulte d'âge moyen, Biopsie, Coloscopie, Femelle, Humains, Résultat thérapeutique, Thérapie moléculaire ciblée, Évolution de la maladie.
English descriptors
- KwdEn :
- Anti-Inflammatory Agents (administration & dosage), Anti-Inflammatory Agents (adverse effects), Antibodies, Monoclonal, Humanized (administration & dosage), Antibodies, Monoclonal, Humanized (adverse effects), Biopsy, Colitis, Ulcerative (diagnosis), Colitis, Ulcerative (drug therapy), Colitis, Ulcerative (genetics), Colitis, Ulcerative (immunology), Colonoscopy, Cytokines (genetics), Cytokines (immunology), Disease Progression, Female, Gastrointestinal Agents (administration & dosage), Gastrointestinal Agents (adverse effects), Humans, Middle Aged, Molecular Targeted Therapy, Receptors, Interleukin-6 (antagonists & inhibitors), Receptors, Interleukin-6 (immunology), Treatment Outcome.
- MESH :
- chemical , administration & dosage : Anti-Inflammatory Agents, Antibodies, Monoclonal, Humanized, Gastrointestinal Agents.
- chemical , adverse effects : Anti-Inflammatory Agents, Antibodies, Monoclonal, Humanized, Gastrointestinal Agents.
- chemical , antagonists & inhibitors : Receptors, Interleukin-6.
- diagnosis : Colitis, Ulcerative.
- drug therapy : Colitis, Ulcerative.
- genetics : Colitis, Ulcerative, Cytokines.
- immunology : Colitis, Ulcerative, Cytokines, Receptors, Interleukin-6.
- Biopsy, Colonoscopy, Disease Progression, Female, Humans, Middle Aged, Molecular Targeted Therapy, Treatment Outcome.
Abstract
We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.
DOI: 10.3748/wjg.v21.i45.12963
PubMed: 26668517
Affiliations:
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pubmed:26668517Le document en format XML
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wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Billmeier, Ulrike" sort="Billmeier, Ulrike" uniqKey="Billmeier U" first="Ulrike" last="Billmeier">Ulrike Billmeier</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Rath, Timo" sort="Rath, Timo" uniqKey="Rath T" first="Timo" last="Rath">Timo Rath</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Mudter, Jonas" sort="Mudter, Jonas" uniqKey="Mudter J" first="Jonas" last="Mudter">Jonas Mudter</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Vieth, Michael" sort="Vieth, Michael" uniqKey="Vieth M" first="Michael" last="Vieth">Michael Vieth</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Neumann, Helmut" sort="Neumann, Helmut" uniqKey="Neumann H" first="Helmut" last="Neumann">Helmut Neumann</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author><author><name sortKey="Neurath, Markus F" sort="Neurath, Markus F" uniqKey="Neurath M" first="Markus F" last="Neurath">Markus F. Neurath</name><affiliation wicri:level="1"><nlm:affiliation>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Raja Atreya, Ulrike Billmeier, Timo Rath, Helmut Neumann, Markus F Neurath, Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen</wicri:regionArea><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>91054 Erlangen</wicri:noRegion><wicri:noRegion>D-91054 Erlangen</wicri:noRegion></affiliation></author></analytic><series><title level="j">World journal of gastroenterology</title><idno type="eISSN">2219-2840</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-Inflammatory Agents (administration & dosage)</term><term>Anti-Inflammatory Agents (adverse effects)</term><term>Antibodies, Monoclonal, Humanized (administration & dosage)</term><term>Antibodies, Monoclonal, Humanized (adverse effects)</term><term>Biopsy</term><term>Colitis, Ulcerative (diagnosis)</term><term>Colitis, Ulcerative (drug therapy)</term><term>Colitis, Ulcerative (genetics)</term><term>Colitis, Ulcerative (immunology)</term><term>Colonoscopy</term><term>Cytokines (genetics)</term><term>Cytokines (immunology)</term><term>Disease Progression</term><term>Female</term><term>Gastrointestinal Agents (administration & dosage)</term><term>Gastrointestinal Agents (adverse effects)</term><term>Humans</term><term>Middle Aged</term><term>Molecular Targeted Therapy</term><term>Receptors, Interleukin-6 (antagonists & inhibitors)</term><term>Receptors, Interleukin-6 (immunology)</term><term>Treatment Outcome</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Agents gastro-intestinaux (administration et posologie)</term><term>Agents gastro-intestinaux (effets indésirables)</term><term>Anti-inflammatoires (administration et posologie)</term><term>Anti-inflammatoires (effets indésirables)</term><term>Anticorps monoclonaux humanisés (administration et posologie)</term><term>Anticorps monoclonaux humanisés (effets indésirables)</term><term>Biopsie</term><term>Coloscopie</term><term>Cytokines (génétique)</term><term>Cytokines (immunologie)</term><term>Femelle</term><term>Humains</term><term>Rectocolite hémorragique (diagnostic)</term><term>Rectocolite hémorragique (génétique)</term><term>Rectocolite hémorragique (immunologie)</term><term>Rectocolite hémorragique (traitement médicamenteux)</term><term>Récepteurs à l'interleukine-6 (antagonistes et inhibiteurs)</term><term>Récepteurs à l'interleukine-6 (immunologie)</term><term>Résultat thérapeutique</term><term>Thérapie moléculaire ciblée</term><term>Évolution de la maladie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Antibodies, Monoclonal, Humanized</term><term>Gastrointestinal Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Antibodies, Monoclonal, Humanized</term><term>Gastrointestinal Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptors, Interleukin-6</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Agents gastro-intestinaux</term><term>Anti-inflammatoires</term><term>Anticorps monoclonaux humanisés</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteurs à l'interleukine-6</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Colitis, Ulcerative</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Rectocolite hémorragique</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Colitis, Ulcerative</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Agents gastro-intestinaux</term><term>Anti-inflammatoires</term><term>Anticorps monoclonaux humanisés</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Colitis, Ulcerative</term><term>Cytokines</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cytokines</term><term>Rectocolite hémorragique</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytokines</term><term>Rectocolite hémorragique</term><term>Récepteurs à l'interleukine-6</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Colitis, Ulcerative</term><term>Cytokines</term><term>Receptors, Interleukin-6</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Rectocolite hémorragique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Biopsy</term><term>Colonoscopy</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Middle Aged</term><term>Molecular Targeted Therapy</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Biopsie</term><term>Coloscopie</term><term>Femelle</term><term>Humains</term><term>Résultat thérapeutique</term><term>Thérapie moléculaire ciblée</term><term>Évolution de la maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. </div></front></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Atreya, Raja" sort="Atreya, Raja" uniqKey="Atreya R" first="Raja" last="Atreya">Raja Atreya</name></noRegion><name sortKey="Billmeier, Ulrike" sort="Billmeier, Ulrike" uniqKey="Billmeier U" first="Ulrike" last="Billmeier">Ulrike Billmeier</name><name sortKey="Mudter, Jonas" sort="Mudter, Jonas" uniqKey="Mudter J" first="Jonas" last="Mudter">Jonas Mudter</name><name sortKey="Neumann, Helmut" sort="Neumann, Helmut" uniqKey="Neumann H" first="Helmut" last="Neumann">Helmut Neumann</name><name sortKey="Neurath, Markus F" sort="Neurath, Markus F" uniqKey="Neurath M" first="Markus F" last="Neurath">Markus F. Neurath</name><name sortKey="Rath, Timo" sort="Rath, Timo" uniqKey="Rath T" first="Timo" last="Rath">Timo Rath</name><name sortKey="Vieth, Michael" sort="Vieth, Michael" uniqKey="Vieth M" first="Michael" last="Vieth">Michael Vieth</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/TocilizumabV1/Data/2020/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000624 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/2020/Analysis/biblio.hfd -nk 000624 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= TocilizumabV1
|flux= 2020
|étape= Analysis
|type= RBID
|clé= pubmed:26668517
|texte= First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/2020/Analysis/RBID.i -Sk "pubmed:26668517" \
| HfdSelect -Kh $EXPLOR_AREA/Data/2020/Analysis/biblio.hfd \
| NlmPubMed2Wicri -a TocilizumabV1
| This area was generated with Dilib version V0.6.34. |  |