PMID- 24834925 OWN - NLM STAT- MEDLINE DCOM- 20150728 LR - 20220408 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 74 IP - 6 DP - 2015 Jun TI - Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. PG - 1110-7 LID - 10.1136/annrheumdis-2014-205351 [doi] AB - 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. CI - 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. FAU - Brunner, Hermine I AU - Brunner HI AD - Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA. FAU - Ruperto, Nicolino AU - Ruperto N AD - Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy. FAU - Zuber, Zbigniew AU - Zuber Z AD - Department of Pediatric Neurology and Rheumatology, St. Louis Children's Hospital, Cracow, Poland. FAU - Keane, Caroline AU - Keane C AD - Roche Products Ltd, Welwyn Garden City, UK. FAU - Harari, Olivier AU - Harari O AD - Roche Products Ltd, Welwyn Garden City, UK. FAU - Kenwright, Andrew AU - Kenwright A AD - Roche Products Ltd, Welwyn Garden City, UK. FAU - Lu, Peng AU - Lu P AD - Roche, Nutley, New Jersey, USA. FAU - Cuttica, Ruben AU - Cuttica R AD - Hospital General de Ninos Pedro de Elizalde, Buenos Aires, Argentina. FAU - Keltsev, Vladimir AU - Keltsev V AD - Department of Pediatric Cardiology and Rheumatology, Samara Regional Clinical Hospital, Samara, Russia. FAU - Xavier, Ricardo M AU - Xavier RM AD - Rheumatology Service, Department of Internal Medicine, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Calvo, Inmaculada AU - Calvo I AD - Paediatric Rheumatology Department, Hospital Universitario La Fe, Valencia, Spain. FAU - Nikishina, Irina AU - Nikishina I AD - Pediatric Department, Federal State Budgetary Institution (Research Institute of Rheumatology named after V.A. Nasonova) under the Russian Academy of Medical Sciences, Moscow, Russia. FAU - Rubio-Perez, Nadina AU - Rubio-Perez N AD - Department of Pediatrics, Hospital Universitario, Universidad Autonoma de Nuevo Leon, Nuevo Leon, Mexico. FAU - Alexeeva, Ekaterina AU - Alexeeva E AD - Scientific Center, Children's Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russia. FAU - Chasnyk, Vyacheslav AU - Chasnyk V AD - St Petersburg State Pediatric Medical Academy, St Petersburg, Russia. FAU - Horneff, Gerd AU - Horneff G AD - Asklepios Klinik Sankt Augustin, Centre for General Pediatrics and Neonatology, Sankt Augustin, Germany. FAU - Opoka-Winiarska, Violetta AU - Opoka-Winiarska V AD - Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, Lublin, Poland. FAU - Quartier, Pierre AU - Quartier P AD - Unite d'Immunologie, Hematologie et Rhumatologie Pediatrique, Universite Paris-Descartes, Hopital Necker-Enfants Malades and Institut IMAGINE, Paris, France. FAU - Silva, Clovis A AU - Silva CA AD - Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de Sao Paulo, Children's Institute, Sao Paulo, Brazil. FAU - Silverman, Earl AU - Silverman E AD - Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. FAU - Spindler, Alberto AU - Spindler A AD - Department of Medicine, Universidad Nacional de Tucuman, Tucuman, Argentina. FAU - Baildam, Eileen AU - Baildam E AD - Department of Paediatric Rheumatology, Alder Hey Children's Foundation NHS Trust, Liverpool, UK. FAU - Gamir, M Luz AU - Gamir ML AD - Servicio de Reumatologia, Hospital Universitario Ramon y Cajal, Madrid, Spain. FAU - Martin, Alan AU - Martin A AD - Tulsa Bone & Joint Associates, Tulsa, Oklahoma, USA. FAU - Rietschel, Christoph AU - Rietschel C AD - Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhauser, Frankfurt, Germany. FAU - Siri, Daniel AU - Siri D AD - CAICI Institute, Rosario, Argentina. FAU - Smolewska, Elzbieta AU - Smolewska E AD - Department of Pediatric Cardiology and Rheumatology, Medical University of Lodz, Lodz, Poland. FAU - Lovell, Daniel AU - Lovell D AD - Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA. FAU - Martini, Alberto AU - Martini A AD - Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy Dipartimento di Pediatria, Universita di Genova, Genoa, Italy. FAU - De Benedetti, Fabrizio AU - De Benedetti F AD - Ospedale Pediatrico Bambino Gesu, Rome, Italy. CN - Paediatric Rheumatology International Trials Organisation PRINTO CN - Pediatric Rheumatology Collaborative Study Group (PRCSG) LA - eng SI - ClinicalTrials.gov/NCT00988221 GR - UL1 TR001425/TR/NCATS NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140516 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Receptors, Interleukin-6) RN - I031V2H011 (tocilizumab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adolescent MH - Adrenal Cortex Hormones/therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Juvenile/*drug therapy MH - Bronchitis/chemically induced MH - Cellulitis/chemically induced MH - Child MH - Child, Preschool MH - Disease Progression MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Humans MH - Maintenance Chemotherapy/*methods MH - Male MH - Methotrexate/therapeutic use MH - Pneumonia/chemically induced MH - Receptors, Interleukin-6/*antagonists & inhibitors MH - Remission Induction/methods MH - Treatment Outcome PMC - PMC4431348 OTO - NOTNLM OT - DMARDs (biologic) OT - Juvenile Idiopathic Arthritis OT - Treatment FIR - Espada, Graciela IR - Espada G FIR - Allen, Roger IR - Allen R FIR - Chaitow, Jeffrey IR - Chaitow J FIR - Joos, Rik IR - Joos R FIR - Wouters, Carine IR - Wouters C FIR - Knupp, Sheila IR - Knupp S FIR - Sztajnbok, Flavio IR - Sztajnbok F FIR - Cabral, David IR - Cabral D FIR - Houghton, Kristin IR - Houghton K FIR - Roth, Johannes IR - Roth J FIR - Schmeling, Heinrike IR - Schmeling H FIR - Job-Deslandre, Chantal IR - Job-Deslandre C FIR - Jorgensen, Christian IR - Jorgensen C FIR - Paut, Isabelle Kone IR - Paut IK FIR - Minden, Kirsten IR - Minden K FIR - Weller-Heinemann, Frank IR - Weller-Heinemann F FIR - Gerloni, Valeria IR - Gerloni V FIR - Zulian, Francesco IR - Zulian F FIR - Burgos-Vargas, Ruben IR - Burgos-Vargas R FIR - Salazar, Carolina Duarte IR - Salazar CD FIR - Solis-Vallejo, Eunice IR - Solis-Vallejo E FIR - Calvo, Armando IR - Calvo A FIR - Chavez, Jose IR - Chavez J FIR - Zavaler, Manuel Ferrandiz IR - Zavaler MF FIR - Gruenpeter, Anna IR - Gruenpeter A FIR - Kobusinska, Katarzyna IR - Kobusinska K FIR - Sarychev, Alexey IR - Sarychev A FIR - Zholobova, Elena IR - Zholobova E FIR - Ramanan, Athimalaipet IR - Ramanan A FIR - Woo, Patricia IR - Woo P FIR - Goodman, Steven IR - Goodman S FIR - Gedalia, Abraham IR - Gedalia A FIR - Kimura, Yukiko IR - Kimura Y FIR - Onel, Karen IR - Onel K FIR - Schikler, Kenneth IR - Schikler K EDAT- 2014/05/20 06:00 MHDA- 2015/07/29 06:00 PMCR- 2015/05/14 CRDT- 2014/05/20 06:00 PHST- 2014/02/04 00:00 [received] PHST- 2014/04/16 00:00 [accepted] PHST- 2014/05/20 06:00 [entrez] PHST- 2014/05/20 06:00 [pubmed] PHST- 2015/07/29 06:00 [medline] PHST- 2015/05/14 00:00 [pmc-release] AID - annrheumdis-2014-205351 [pii] AID - 10.1136/annrheumdis-2014-205351 [doi] PST - ppublish SO - Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.