Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
Summary Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Me...
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| Veröffentlicht in: | The Lancet (British edition) 2008-03, Vol.371 (9617), p.998-1006 |
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| creator | Yokota, Shumpei, Prof Imagawa, Tomoyuki, MD Mori, Masaaki, MD Miyamae, Takako, MD Aihara, Yukoh, MD Takei, Shuji, Prof Iwata, Naomi, MD Umebayashi, Hiroaki, MD Murata, Takuji, MD Miyoshi, Mari, MD Tomiita, Minako, MD Nishimoto, Norihiro, Prof Kishimoto, Tadamitsu, Prof |
| description | Summary Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2–19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p |
| doi_str_mv | 10.1016/S0140-6736(08)60454-7 |
| format | Article |
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We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2–19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0·0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. Interpretation Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage. Funding Chugai Pharmaceuticals.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(08)60454-7</identifier><identifier>PMID: 18358927</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized ; Arthritis ; Arthritis, Juvenile - drug therapy ; Arthritis, Juvenile - physiopathology ; C-Reactive Protein - drug effects ; C-Reactive Protein - metabolism ; Child ; Child, Preschool ; Children & youth ; Clinical trials ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug therapy ; Female ; Gastroenteritis ; Hospitals ; Humans ; Internal Medicine ; Japan ; Male ; Medical treatment ; Monoclonal antibodies ; Patients ; Pharmaceuticals ; Receptors, Interleukin-6 - antagonists & inhibitors ; Rheumatology ; Sample size ; Tomography ; Treatment Outcome ; Variables</subject><ispartof>The Lancet (British edition), 2008-03, Vol.371 (9617), p.998-1006</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Mar 22-Mar 28, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-92b5eaa98d41d1854806bc433a884175cef3981ad5ee1ddc123e8b29e1c63fb23</citedby><cites>FETCH-LOGICAL-c445t-92b5eaa98d41d1854806bc433a884175cef3981ad5ee1ddc123e8b29e1c63fb23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673608604547$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18358927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yokota, Shumpei, Prof</creatorcontrib><creatorcontrib>Imagawa, Tomoyuki, MD</creatorcontrib><creatorcontrib>Mori, Masaaki, MD</creatorcontrib><creatorcontrib>Miyamae, Takako, MD</creatorcontrib><creatorcontrib>Aihara, Yukoh, MD</creatorcontrib><creatorcontrib>Takei, Shuji, Prof</creatorcontrib><creatorcontrib>Iwata, Naomi, MD</creatorcontrib><creatorcontrib>Umebayashi, Hiroaki, MD</creatorcontrib><creatorcontrib>Murata, Takuji, MD</creatorcontrib><creatorcontrib>Miyoshi, Mari, MD</creatorcontrib><creatorcontrib>Tomiita, Minako, MD</creatorcontrib><creatorcontrib>Nishimoto, Norihiro, Prof</creatorcontrib><creatorcontrib>Kishimoto, Tadamitsu, Prof</creatorcontrib><title>Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2–19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0·0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. Interpretation Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage. Funding Chugai Pharmaceuticals.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Arthritis</subject><subject>Arthritis, Juvenile - drug therapy</subject><subject>Arthritis, Juvenile - physiopathology</subject><subject>C-Reactive Protein - drug effects</subject><subject>C-Reactive Protein - metabolism</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children & youth</subject><subject>Clinical trials</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Gastroenteritis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Japan</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Pharmaceuticals</subject><subject>Receptors, Interleukin-6 - antagonists & inhibitors</subject><subject>Rheumatology</subject><subject>Sample size</subject><subject>Tomography</subject><subject>Treatment 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and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial</title><author>Yokota, Shumpei, Prof ; Imagawa, Tomoyuki, MD ; Mori, Masaaki, MD ; Miyamae, Takako, MD ; Aihara, Yukoh, MD ; Takei, Shuji, Prof ; Iwata, Naomi, MD ; Umebayashi, Hiroaki, MD ; Murata, Takuji, MD ; Miyoshi, Mari, MD ; Tomiita, Minako, MD ; Nishimoto, Norihiro, Prof ; Kishimoto, Tadamitsu, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-92b5eaa98d41d1854806bc433a884175cef3981ad5ee1ddc123e8b29e1c63fb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Arthritis</topic><topic>Arthritis, Juvenile - drug therapy</topic><topic>Arthritis, Juvenile - physiopathology</topic><topic>C-Reactive Protein - drug effects</topic><topic>C-Reactive Protein - metabolism</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children & youth</topic><topic>Clinical trials</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Gastroenteritis</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Japan</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Pharmaceuticals</topic><topic>Receptors, Interleukin-6 - antagonists & inhibitors</topic><topic>Rheumatology</topic><topic>Sample size</topic><topic>Tomography</topic><topic>Treatment 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Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yokota, Shumpei, Prof</au><au>Imagawa, Tomoyuki, MD</au><au>Mori, Masaaki, MD</au><au>Miyamae, Takako, MD</au><au>Aihara, Yukoh, MD</au><au>Takei, Shuji, Prof</au><au>Iwata, Naomi, MD</au><au>Umebayashi, Hiroaki, MD</au><au>Murata, Takuji, MD</au><au>Miyoshi, Mari, MD</au><au>Tomiita, Minako, MD</au><au>Nishimoto, Norihiro, Prof</au><au>Kishimoto, Tadamitsu, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2008-03-22</date><risdate>2008</risdate><volume>371</volume><issue>9617</issue><spage>998</spage><epage>1006</epage><pages>998-1006</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. Methods 56 children (aged 2–19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). Findings At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0·0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. Interpretation Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage. Funding Chugai Pharmaceuticals.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>18358927</pmid><doi>10.1016/S0140-6736(08)60454-7</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2008-03, Vol.371 (9617), p.998-1006 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70421956 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized Arthritis Arthritis, Juvenile - drug therapy Arthritis, Juvenile - physiopathology C-Reactive Protein - drug effects C-Reactive Protein - metabolism Child Child, Preschool Children & youth Clinical trials Dose-Response Relationship, Drug Double-Blind Method Drug therapy Female Gastroenteritis Hospitals Humans Internal Medicine Japan Male Medical treatment Monoclonal antibodies Patients Pharmaceuticals Receptors, Interleukin-6 - antagonists & inhibitors Rheumatology Sample size Tomography Treatment Outcome Variables |
| title | Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T05%3A28%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20safety%20of%20tocilizumab%20in%20patients%20with%20systemic-onset%20juvenile%20idiopathic%20arthritis:%20a%20randomised,%20double-blind,%20placebo-controlled,%20withdrawal%20phase%20III%20trial&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Yokota,%20Shumpei,%20Prof&rft.date=2008-03-22&rft.volume=371&rft.issue=9617&rft.spage=998&rft.epage=1006&rft.pages=998-1006&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(08)60454-7&rft_dat=%3Cproquest_cross%3E70421956%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=199016925&rft_id=info:pmid/18358927&rft_els_id=S0140673608604547&rfr_iscdi=true |