Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study
Summary Background Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. Aims This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as ma...
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| Veröffentlicht in: | Alimentary pharmacology & therapeutics 2019-02, Vol.49 (3), p.265-276 |
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| creator | Panés, Julián D’Haens, Geert R. Higgins, Peter D. R. Mele, Linda Moscariello, Michele Chan, Gary Wang, Wenjin Niezychowski, Wojciech Su, Chinyu Maller, Eric |
| description | Summary
Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.
Aims
This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.
Methods
Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index |
| doi_str_mv | 10.1111/apt.15072 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6646954</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2179381088</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4432-a9d34787cff815c5c9fd241ae815b3385659310e4781de63a9f9122f9f1e3a633</originalsourceid><addsrcrecordid>eNp1kc1u1DAUhS0EokNhwQsgS2xAalr_JI7DAqka8SeNBIuytpzkuuPisYPtMMyuj9At4u36JBimVICEN7bP_XR0jw5Cjyk5puWc6Ckf04a07A5aUC6aihEu7qIFYaKrmKT8AD1I6YIQIlrC7qMDToTglLQL9H0V_Pn15VWGuMFJG8g7rP2Ic3AQdW-dLUIwOETtimj0YLP1tsfW40lnCz4nvLV5jZcxrP315beER5tAJ3iBI6TZlbmJYYM1ntZFxewIhwkKeeV0D-4I17K8twCfMHzN4JMNHqc8j7uH6J7RLsGjm_sQfXz96mz5tlq9f_NuebqqhrrmrNLdyOtWtoMxkjZDM3RmZDXVUH4957IRTVfCQmHoCILrznSUMdMZClwLzg_Ry73vNPcbGIeSqaRVU7QbHXcqaKv-nni7VufhixKiFl1TF4NnNwYxfJ4hZbWxaQDntIcwJ8Vo23FJiZQFffoPehHm6Eu8QgnZSslEW6jne2qIIaUI5nYZStTPylWpXP2qvLBP_tz-lvzdcQFO9sDWOtj930mdfjjbW_4AyRO7XQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2168788267</pqid></control><display><type>article</type><title>Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study</title><source>MEDLINE</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><creator>Panés, Julián ; D’Haens, Geert R. ; Higgins, Peter D. R. ; Mele, Linda ; Moscariello, Michele ; Chan, Gary ; Wang, Wenjin ; Niezychowski, Wojciech ; Su, Chinyu ; Maller, Eric</creator><creatorcontrib>Panés, Julián ; D’Haens, Geert R. ; Higgins, Peter D. R. ; Mele, Linda ; Moscariello, Michele ; Chan, Gary ; Wang, Wenjin ; Niezychowski, Wojciech ; Su, Chinyu ; Maller, Eric</creatorcontrib><description>Summary
Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.
Aims
This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.
Methods
Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks’ fixed, open‐label treatment.
Results
Sixty‐two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non‐responder imputation). Study design prevented between‐dose efficacy comparisons.
Conclusions
No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.</description><identifier>ISSN: 0269-2813</identifier><identifier>ISSN: 1365-2036</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.15072</identifier><identifier>PMID: 30663107</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Crohn Disease - drug therapy ; Crohn's disease ; Enzyme inhibitors ; Female ; Humans ; Inflammatory bowel diseases ; Intestine ; Janus kinase ; Middle Aged ; Original ; Patients ; Piperidines - administration & dosage ; Piperidines - adverse effects ; Protein Kinase Inhibitors - adverse effects ; Protein Kinase Inhibitors - therapeutic use ; Pyrimidines - administration & dosage ; Pyrimidines - adverse effects ; Pyrroles - administration & dosage ; Pyrroles - adverse effects ; Remission ; Safety ; Safety of Tofacitinib in Crohn's Disease</subject><ispartof>Alimentary pharmacology & therapeutics, 2019-02, Vol.49 (3), p.265-276</ispartof><rights>2019 John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons Ltd.</rights><rights>Copyright © 2019 John Wiley & Sons Ltd</rights><rights>2019 The Authors. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4432-a9d34787cff815c5c9fd241ae815b3385659310e4781de63a9f9122f9f1e3a633</citedby><cites>FETCH-LOGICAL-c4432-a9d34787cff815c5c9fd241ae815b3385659310e4781de63a9f9122f9f1e3a633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapt.15072$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapt.15072$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1416,1432,27922,27923,45572,45573,46407,46831</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30663107$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Panés, Julián</creatorcontrib><creatorcontrib>D’Haens, Geert R.</creatorcontrib><creatorcontrib>Higgins, Peter D. R.</creatorcontrib><creatorcontrib>Mele, Linda</creatorcontrib><creatorcontrib>Moscariello, Michele</creatorcontrib><creatorcontrib>Chan, Gary</creatorcontrib><creatorcontrib>Wang, Wenjin</creatorcontrib><creatorcontrib>Niezychowski, Wojciech</creatorcontrib><creatorcontrib>Su, Chinyu</creatorcontrib><creatorcontrib>Maller, Eric</creatorcontrib><title>Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary
Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.
Aims
This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.
Methods
Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks’ fixed, open‐label treatment.
Results
Sixty‐two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non‐responder imputation). Study design prevented between‐dose efficacy comparisons.
Conclusions
No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.</description><subject>Adult</subject><subject>Crohn Disease - drug therapy</subject><subject>Crohn's disease</subject><subject>Enzyme inhibitors</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammatory bowel diseases</subject><subject>Intestine</subject><subject>Janus kinase</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Patients</subject><subject>Piperidines - administration & dosage</subject><subject>Piperidines - adverse effects</subject><subject>Protein Kinase Inhibitors - adverse effects</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Pyrimidines - administration & dosage</subject><subject>Pyrimidines - adverse effects</subject><subject>Pyrroles - administration & dosage</subject><subject>Pyrroles - adverse effects</subject><subject>Remission</subject><subject>Safety</subject><subject>Safety of Tofacitinib in Crohn's Disease</subject><issn>0269-2813</issn><issn>1365-2036</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EokNhwQsgS2xAalr_JI7DAqka8SeNBIuytpzkuuPisYPtMMyuj9At4u36JBimVICEN7bP_XR0jw5Cjyk5puWc6Ckf04a07A5aUC6aihEu7qIFYaKrmKT8AD1I6YIQIlrC7qMDToTglLQL9H0V_Pn15VWGuMFJG8g7rP2Ic3AQdW-dLUIwOETtimj0YLP1tsfW40lnCz4nvLV5jZcxrP315beER5tAJ3iBI6TZlbmJYYM1ntZFxewIhwkKeeV0D-4I17K8twCfMHzN4JMNHqc8j7uH6J7RLsGjm_sQfXz96mz5tlq9f_NuebqqhrrmrNLdyOtWtoMxkjZDM3RmZDXVUH4957IRTVfCQmHoCILrznSUMdMZClwLzg_Ry73vNPcbGIeSqaRVU7QbHXcqaKv-nni7VufhixKiFl1TF4NnNwYxfJ4hZbWxaQDntIcwJ8Vo23FJiZQFffoPehHm6Eu8QgnZSslEW6jne2qIIaUI5nYZStTPylWpXP2qvLBP_tz-lvzdcQFO9sDWOtj930mdfjjbW_4AyRO7XQ</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Panés, Julián</creator><creator>D’Haens, Geert R.</creator><creator>Higgins, Peter D. R.</creator><creator>Mele, Linda</creator><creator>Moscariello, Michele</creator><creator>Chan, Gary</creator><creator>Wang, Wenjin</creator><creator>Niezychowski, Wojciech</creator><creator>Su, Chinyu</creator><creator>Maller, Eric</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201902</creationdate><title>Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study</title><author>Panés, Julián ; D’Haens, Geert R. ; Higgins, Peter D. R. ; Mele, Linda ; Moscariello, Michele ; Chan, Gary ; Wang, Wenjin ; Niezychowski, Wojciech ; Su, Chinyu ; Maller, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4432-a9d34787cff815c5c9fd241ae815b3385659310e4781de63a9f9122f9f1e3a633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Crohn Disease - drug therapy</topic><topic>Crohn's disease</topic><topic>Enzyme inhibitors</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammatory bowel diseases</topic><topic>Intestine</topic><topic>Janus kinase</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Patients</topic><topic>Piperidines - administration & dosage</topic><topic>Piperidines - adverse effects</topic><topic>Protein Kinase Inhibitors - adverse effects</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Pyrimidines - administration & dosage</topic><topic>Pyrimidines - adverse effects</topic><topic>Pyrroles - administration & dosage</topic><topic>Pyrroles - adverse effects</topic><topic>Remission</topic><topic>Safety</topic><topic>Safety of Tofacitinib in Crohn's Disease</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Panés, Julián</creatorcontrib><creatorcontrib>D’Haens, Geert R.</creatorcontrib><creatorcontrib>Higgins, Peter D. R.</creatorcontrib><creatorcontrib>Mele, Linda</creatorcontrib><creatorcontrib>Moscariello, Michele</creatorcontrib><creatorcontrib>Chan, Gary</creatorcontrib><creatorcontrib>Wang, Wenjin</creatorcontrib><creatorcontrib>Niezychowski, Wojciech</creatorcontrib><creatorcontrib>Su, Chinyu</creatorcontrib><creatorcontrib>Maller, Eric</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Panés, Julián</au><au>D’Haens, Geert R.</au><au>Higgins, Peter D. R.</au><au>Mele, Linda</au><au>Moscariello, Michele</au><au>Chan, Gary</au><au>Wang, Wenjin</au><au>Niezychowski, Wojciech</au><au>Su, Chinyu</au><au>Maller, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2019-02</date><risdate>2019</risdate><volume>49</volume><issue>3</issue><spage>265</spage><epage>276</epage><pages>265-276</pages><issn>0269-2813</issn><issn>1365-2036</issn><eissn>1365-2036</eissn><abstract>Summary
Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.
Aims
This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.
Methods
Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks’ fixed, open‐label treatment.
Results
Sixty‐two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non‐responder imputation). Study design prevented between‐dose efficacy comparisons.
Conclusions
No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30663107</pmid><doi>10.1111/apt.15072</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0269-2813 |
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| source | MEDLINE; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals |
| subjects | Adult Crohn Disease - drug therapy Crohn's disease Enzyme inhibitors Female Humans Inflammatory bowel diseases Intestine Janus kinase Middle Aged Original Patients Piperidines - administration & dosage Piperidines - adverse effects Protein Kinase Inhibitors - adverse effects Protein Kinase Inhibitors - therapeutic use Pyrimidines - administration & dosage Pyrimidines - adverse effects Pyrroles - administration & dosage Pyrroles - adverse effects Remission Safety Safety of Tofacitinib in Crohn's Disease |
| title | Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study |
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