Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial
Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2015-06, Vol.74 (6), p.1110-1117 |
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| creator | Brunner, Hermine I Ruperto, Nicolino Zuber, Zbigniew Keane, Caroline Harari, Olivier Kenwright, Andrew Lu, Peng Cuttica, Ruben Keltsev, Vladimir Xavier, Ricardo M Calvo, Inmaculada Nikishina, Irina Rubio-Pérez, Nadina Alexeeva, Ekaterina Chasnyk, Vyacheslav Horneff, Gerd Opoka-Winiarska, Violetta Quartier, Pierre Silva, Clovis A Silverman, Earl Spindler, Alberto Baildam, Eileen Gámir, M Luz Martin, Alan Rietschel, Christoph Siri, Daniel Smolewska, Elzbieta Lovell, Daniel Martini, Alberto De Benedetti, Fabrizio |
| description | Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) |
| doi_str_mv | 10.1136/annrheumdis-2014-205351 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4431348</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4008712751</sourcerecordid><originalsourceid>FETCH-LOGICAL-b617t-a8a0f6d4189291bb74bafb79e48e3086b2ed1499cb029b903b0c78361e8135253</originalsourceid><addsrcrecordid>eNqNkstu1DAUhi0EosPAK4AlNiwa8C2JzQIJVeUiVWIDa-vYcYhHTjzYcavhjXhLPJpSFVZsbB35O5f_-EfoBSWvKeXdG1iWNLkyDz43jFBRj5a39AHaUNHJGnXkIdoQQngjVNefoSc572pIJJWP0RkTkgvF2g36dTmO3oI9YFgGnGF06wHHEa_R-uB_lhkM9gvew-rdsmZ849cJ72M4QFq9LQFSY2NJ2eFduXaLDw77wcfKT97iCk3Jrz6_xcnlEmqBMcUZA95PUHP4OU61b5x9dsM5HmIxwTUm-DrLsdOQ4AYCXpOH8BQ9GiFk9-z23qJvHy6_Xnxqrr58_Hzx_qoxHe3XBiSQsRsElYopakwvDIymV05Ix4nsDHMDFUpZQ5gyinBDbC95R52kvGUt36J3p7r7YmY32Co7QdD75GdIBx3B679fFj_p7_FaC8Epr4vdole3BVL8UVxedZVnXQiwuFiyprKO0basYxV9-Q-6q8tcqjxN-75XlFClKtWfKJtizsmNd8NQoo920PfsoI920Cc71Mzn97Xc5f35_wqwE2Dm3X9X_Q2Nlcly</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1777910199</pqid></control><display><type>article</type><title>Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><creator>Brunner, Hermine I ; Ruperto, Nicolino ; Zuber, Zbigniew ; Keane, Caroline ; Harari, Olivier ; Kenwright, Andrew ; Lu, Peng ; Cuttica, Ruben ; Keltsev, Vladimir ; Xavier, Ricardo M ; Calvo, Inmaculada ; Nikishina, Irina ; Rubio-Pérez, Nadina ; Alexeeva, Ekaterina ; Chasnyk, Vyacheslav ; Horneff, Gerd ; Opoka-Winiarska, Violetta ; Quartier, Pierre ; Silva, Clovis A ; Silverman, Earl ; Spindler, Alberto ; Baildam, Eileen ; Gámir, M Luz ; Martin, Alan ; Rietschel, Christoph ; Siri, Daniel ; Smolewska, Elzbieta ; Lovell, Daniel ; Martini, Alberto ; De Benedetti, Fabrizio</creator><creatorcontrib>Brunner, Hermine I ; Ruperto, Nicolino ; Zuber, Zbigniew ; Keane, Caroline ; Harari, Olivier ; Kenwright, Andrew ; Lu, Peng ; Cuttica, Ruben ; Keltsev, Vladimir ; Xavier, Ricardo M ; Calvo, Inmaculada ; Nikishina, Irina ; Rubio-Pérez, Nadina ; Alexeeva, Ekaterina ; Chasnyk, Vyacheslav ; Horneff, Gerd ; Opoka-Winiarska, Violetta ; Quartier, Pierre ; Silva, Clovis A ; Silverman, Earl ; Spindler, Alberto ; Baildam, Eileen ; Gámir, M Luz ; Martin, Alan ; Rietschel, Christoph ; Siri, Daniel ; Smolewska, Elzbieta ; Lovell, Daniel ; Martini, Alberto ; De Benedetti, Fabrizio ; Paediatric Rheumatology International Trials Organisation PRINTO ; Pediatric Rheumatology Collaborative Study Group (PRCSG)</creatorcontrib><description>Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2014-205351</identifier><identifier>PMID: 24834925</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Adolescent ; Adrenal Cortex Hormones - therapeutic use ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antirheumatic Agents - therapeutic use ; Arthritis ; Arthritis, Juvenile - drug therapy ; Bronchitis - chemically induced ; Cellulitis - chemically induced ; Child ; Child, Preschool ; Cholesterol ; Clinical and Epidemiological Research ; Disease Progression ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Low density lipoprotein ; Maintenance Chemotherapy - methods ; Male ; Methotrexate - therapeutic use ; Pneumonia - chemically induced ; Receptors, Interleukin-6 - antagonists & inhibitors ; Remission Induction - methods ; Rheumatology ; Treatment Outcome</subject><ispartof>Annals of the rheumatic diseases, 2015-06, Vol.74 (6), p.1110-1117</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>Copyright: 2015 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b617t-a8a0f6d4189291bb74bafb79e48e3086b2ed1499cb029b903b0c78361e8135253</citedby><cites>FETCH-LOGICAL-b617t-a8a0f6d4189291bb74bafb79e48e3086b2ed1499cb029b903b0c78361e8135253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/74/6/1110.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/74/6/1110.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>114,115,230,314,776,780,881,3183,23550,27901,27902,77569,77600</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24834925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brunner, Hermine I</creatorcontrib><creatorcontrib>Ruperto, Nicolino</creatorcontrib><creatorcontrib>Zuber, Zbigniew</creatorcontrib><creatorcontrib>Keane, Caroline</creatorcontrib><creatorcontrib>Harari, Olivier</creatorcontrib><creatorcontrib>Kenwright, Andrew</creatorcontrib><creatorcontrib>Lu, Peng</creatorcontrib><creatorcontrib>Cuttica, Ruben</creatorcontrib><creatorcontrib>Keltsev, Vladimir</creatorcontrib><creatorcontrib>Xavier, Ricardo M</creatorcontrib><creatorcontrib>Calvo, Inmaculada</creatorcontrib><creatorcontrib>Nikishina, Irina</creatorcontrib><creatorcontrib>Rubio-Pérez, Nadina</creatorcontrib><creatorcontrib>Alexeeva, Ekaterina</creatorcontrib><creatorcontrib>Chasnyk, Vyacheslav</creatorcontrib><creatorcontrib>Horneff, Gerd</creatorcontrib><creatorcontrib>Opoka-Winiarska, Violetta</creatorcontrib><creatorcontrib>Quartier, Pierre</creatorcontrib><creatorcontrib>Silva, Clovis A</creatorcontrib><creatorcontrib>Silverman, Earl</creatorcontrib><creatorcontrib>Spindler, Alberto</creatorcontrib><creatorcontrib>Baildam, Eileen</creatorcontrib><creatorcontrib>Gámir, M Luz</creatorcontrib><creatorcontrib>Martin, Alan</creatorcontrib><creatorcontrib>Rietschel, Christoph</creatorcontrib><creatorcontrib>Siri, Daniel</creatorcontrib><creatorcontrib>Smolewska, Elzbieta</creatorcontrib><creatorcontrib>Lovell, Daniel</creatorcontrib><creatorcontrib>Martini, Alberto</creatorcontrib><creatorcontrib>De Benedetti, Fabrizio</creatorcontrib><creatorcontrib>Paediatric Rheumatology International Trials Organisation PRINTO</creatorcontrib><creatorcontrib>Pediatric Rheumatology Collaborative Study Group (PRCSG)</creatorcontrib><title>Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.</description><subject>Adolescent</subject><subject>Adrenal Cortex Hormones - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis</subject><subject>Arthritis, Juvenile - drug therapy</subject><subject>Bronchitis - chemically induced</subject><subject>Cellulitis - chemically induced</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cholesterol</subject><subject>Clinical and Epidemiological Research</subject><subject>Disease Progression</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Humans</subject><subject>Low density lipoprotein</subject><subject>Maintenance Chemotherapy - methods</subject><subject>Male</subject><subject>Methotrexate - therapeutic use</subject><subject>Pneumonia - chemically induced</subject><subject>Receptors, Interleukin-6 - antagonists & inhibitors</subject><subject>Remission Induction - methods</subject><subject>Rheumatology</subject><subject>Treatment 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and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial</title><author>Brunner, Hermine I ; Ruperto, Nicolino ; Zuber, Zbigniew ; Keane, Caroline ; Harari, Olivier ; Kenwright, Andrew ; Lu, Peng ; Cuttica, Ruben ; Keltsev, Vladimir ; Xavier, Ricardo M ; Calvo, Inmaculada ; Nikishina, Irina ; Rubio-Pérez, Nadina ; Alexeeva, Ekaterina ; Chasnyk, Vyacheslav ; Horneff, Gerd ; Opoka-Winiarska, Violetta ; Quartier, Pierre ; Silva, Clovis A ; Silverman, Earl ; Spindler, Alberto ; Baildam, Eileen ; Gámir, M Luz ; Martin, Alan ; Rietschel, Christoph ; Siri, Daniel ; Smolewska, Elzbieta ; Lovell, Daniel ; Martini, Alberto ; De Benedetti, 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Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brunner, Hermine I</au><au>Ruperto, Nicolino</au><au>Zuber, Zbigniew</au><au>Keane, Caroline</au><au>Harari, Olivier</au><au>Kenwright, Andrew</au><au>Lu, Peng</au><au>Cuttica, Ruben</au><au>Keltsev, Vladimir</au><au>Xavier, Ricardo M</au><au>Calvo, Inmaculada</au><au>Nikishina, Irina</au><au>Rubio-Pérez, Nadina</au><au>Alexeeva, Ekaterina</au><au>Chasnyk, Vyacheslav</au><au>Horneff, Gerd</au><au>Opoka-Winiarska, Violetta</au><au>Quartier, Pierre</au><au>Silva, Clovis A</au><au>Silverman, Earl</au><au>Spindler, Alberto</au><au>Baildam, Eileen</au><au>Gámir, M Luz</au><au>Martin, Alan</au><au>Rietschel, Christoph</au><au>Siri, Daniel</au><au>Smolewska, Elzbieta</au><au>Lovell, Daniel</au><au>Martini, Alberto</au><au>De Benedetti, Fabrizio</au><aucorp>Paediatric Rheumatology International Trials Organisation PRINTO</aucorp><aucorp>Pediatric Rheumatology Collaborative Study Group (PRCSG)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>74</volume><issue>6</issue><spage>1110</spage><epage>1117</epage><pages>1110-1117</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>24834925</pmid><doi>10.1136/annrheumdis-2014-205351</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0003-4967 |
| ispartof | Annals of the rheumatic diseases, 2015-06, Vol.74 (6), p.1110-1117 |
| issn | 0003-4967 1468-2060 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4431348 |
| source | MEDLINE; BMJ Journals - NESLi2 |
| subjects | Adolescent Adrenal Cortex Hormones - therapeutic use Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - therapeutic use Arthritis Arthritis, Juvenile - drug therapy Bronchitis - chemically induced Cellulitis - chemically induced Child Child, Preschool Cholesterol Clinical and Epidemiological Research Disease Progression Double-Blind Method Drug Therapy, Combination Female Humans Low density lipoprotein Maintenance Chemotherapy - methods Male Methotrexate - therapeutic use Pneumonia - chemically induced Receptors, Interleukin-6 - antagonists & inhibitors Remission Induction - methods Rheumatology Treatment Outcome |
| title | Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial |
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