Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis
Background: ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective. One additional treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kinases 1, 2, and 3 with in vitro functional specificity for kinases 1 and 3...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/178620 |
| Acceso en línea: | https://hdl.handle.net/2445/178620 |
| Access Level: | acceso abierto |
| Palabra clave: | Colitis ulcerosa Proteïnes quinases Pirimidines Pirroles Ulcerative colitis Protein kinases Pyrimidines Pyrroles |
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Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitisSandborn, William J.Ghosh, SubrataPanés Díaz, JuliàVranic, IvanaSu, ChinyuRousell, SamanthaNiezychowski, WojciechGuardiola, JordiStudy A3921063 InvestigatorsColitis ulcerosaProteïnes quinasesPirimidinesPirrolesUlcerative colitisProtein kinasesPyrimidinesPyrrolesBackground: ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective. One additional treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kinases 1, 2, and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2, which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2, 4, 7, 9, 15, and 21. These cytokines are integral to lymphocyte activation, function, and proliferation. Methods: in a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis. Patients were randomly assigned to receive tofacitinib at a dose of 0.5 mg, 3 mg, 10 mg, or 15 mg or placebo twice daily for 8 weeks. The primary outcome was a clinical response at 8 weeks, defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity (possible score, 0 to 12, with higher scores indicating more severe disease) of 3 or more and a relative decrease from baseline of 30% or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1. Results: the primary outcome, clinical response at 8 weeks, occurred in 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.39), 3 mg (P=0.55), 10 mg (P=0.10), and 15 mg (P<0.001), respectively, as compared with 42% of patients receiving placebo. Clinical remission (defined as a Mayo score ≤2, with no subscore >1) at 8 weeks occurred in 13%, 33%, 48%, and 41% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.76), 3 mg (P=0.01), 10 mg (P<0.001), and 15 mg (P<0.001), respectively, as compared with 10% of patients receiving placebo. There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol. Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500. Conclusions: patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo. (Funded by Pfizer; ClinicalTrials.gov number, NCT00787202).Massachusetts Medical Society2021202120122021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/178620Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1056/NEJMoa1112168New England Journal of Medicine, 2012, vol. 367, num. 7, p. 616-624https://doi.org/10.1056/NEJMoa1112168(c) Massachusetts Medical Society, 2012info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1786202026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| title |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| spellingShingle |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis Sandborn, William J. Colitis ulcerosa Proteïnes quinases Pirimidines Pirroles Ulcerative colitis Protein kinases Pyrimidines Pyrroles |
| title_short |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| title_full |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| title_fullStr |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| title_full_unstemmed |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| title_sort |
Tofacitinib, an oral janus kinase inhibitor, in active ulcerative colitis |
| dc.creator.none.fl_str_mv |
Sandborn, William J. Ghosh, Subrata Panés Díaz, Julià Vranic, Ivana Su, Chinyu Rousell, Samantha Niezychowski, Wojciech Guardiola, Jordi Study A3921063 Investigators |
| author |
Sandborn, William J. |
| author_facet |
Sandborn, William J. Ghosh, Subrata Panés Díaz, Julià Vranic, Ivana Su, Chinyu Rousell, Samantha Niezychowski, Wojciech Guardiola, Jordi Study A3921063 Investigators |
| author_role |
author |
| author2 |
Ghosh, Subrata Panés Díaz, Julià Vranic, Ivana Su, Chinyu Rousell, Samantha Niezychowski, Wojciech Guardiola, Jordi Study A3921063 Investigators |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
Colitis ulcerosa Proteïnes quinases Pirimidines Pirroles Ulcerative colitis Protein kinases Pyrimidines Pyrroles |
| topic |
Colitis ulcerosa Proteïnes quinases Pirimidines Pirroles Ulcerative colitis Protein kinases Pyrimidines Pyrroles |
| description |
Background: ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective. One additional treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kinases 1, 2, and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2, which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2, 4, 7, 9, 15, and 21. These cytokines are integral to lymphocyte activation, function, and proliferation. Methods: in a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis. Patients were randomly assigned to receive tofacitinib at a dose of 0.5 mg, 3 mg, 10 mg, or 15 mg or placebo twice daily for 8 weeks. The primary outcome was a clinical response at 8 weeks, defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity (possible score, 0 to 12, with higher scores indicating more severe disease) of 3 or more and a relative decrease from baseline of 30% or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1. Results: the primary outcome, clinical response at 8 weeks, occurred in 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.39), 3 mg (P=0.55), 10 mg (P=0.10), and 15 mg (P<0.001), respectively, as compared with 42% of patients receiving placebo. Clinical remission (defined as a Mayo score ≤2, with no subscore >1) at 8 weeks occurred in 13%, 33%, 48%, and 41% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.76), 3 mg (P=0.01), 10 mg (P<0.001), and 15 mg (P<0.001), respectively, as compared with 10% of patients receiving placebo. There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol. Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500. Conclusions: patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo. (Funded by Pfizer; ClinicalTrials.gov number, NCT00787202). |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012 2021 2021 2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/178620 |
| url |
https://hdl.handle.net/2445/178620 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1056/NEJMoa1112168 New England Journal of Medicine, 2012, vol. 367, num. 7, p. 616-624 https://doi.org/10.1056/NEJMoa1112168 |
| dc.rights.none.fl_str_mv |
(c) Massachusetts Medical Society, 2012 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Massachusetts Medical Society, 2012 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
9 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Massachusetts Medical Society |
| publisher.none.fl_str_mv |
Massachusetts Medical Society |
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Articles publicats en revistes (Ciències Clíniques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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