{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T22:20:13Z","timestamp":1773699613549,"version":"3.50.1"},"reference-count":55,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Pediatrics"],"published-print":{"date-parts":[[2014,2]]},"DOI":"10.1016\/j.jpeds.2013.10.029","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T13:15:38Z","timestamp":1385385338000},"page":"231-236","source":"Crossref","is-referenced-by-count":63,"title":["Methotrexate: New Uses for an Old Drug"],"prefix":"10.1016","volume":"164","author":[{"given":"Philip J.","family":"Hashkes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara L.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Cabral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald M.","family":"Laxer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy S.","family":"Paller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Egla","family":"Rabinovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Zulian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpeds.2013.10.029_bib1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000203749","article-title":"Treatment of acute leukemia with amethopterin (4-amino, 10-methyl pteroyl glutamic acid)","volume":"4","author":"Meyer","year":"1950","journal-title":"Acta Haematol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib2","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1056\/NEJM199204163261602","article-title":"Methotrexate in resistant juvenile rheumatoid arthritis. Results of the USA-USSR double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and the Cooperative Children's Study Group","volume":"326","author":"Giannini","year":"1992","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jpeds.2013.10.029_bib3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/acr.20460","article-title":"2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features","volume":"63","author":"Beukelman","year":"2011","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"10.1016\/j.jpeds.2013.10.029_bib4","unstructured":"OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. Oxford Centre for Evidence-Based Medicine. Available at: http:\/\/www.cebm.net\/index.aspx?o=5653. Accessed August 28,\u00a02013."},{"key":"10.1016\/j.jpeds.2013.10.029_bib5","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/art.20288","article-title":"A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate","volume":"50","author":"Ruperto","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib6","first-page":"CD003129","article-title":"Methotrexate for treating juvenile idiopathic arthritis","volume":"3","author":"Takken","year":"2001","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.jpeds.2013.10.029_bib7","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1001\/jama.294.13.1671","article-title":"Medical treatment of juvenile idiopathic arthritis","volume":"294","author":"Hashkes","year":"2005","journal-title":"JAMA"},{"key":"10.1016\/j.jpeds.2013.10.029_bib8","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1136\/ard.2009.120840","article-title":"Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial","volume":"69","author":"Vilca","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib9","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1002\/art.34343","article-title":"Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis","volume":"64","author":"Wallace","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib10","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1002\/1529-0131(200008)43:8<1849::AID-ANR22>3.0.CO;2-F","article-title":"Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis","volume":"43","author":"Woo","year":"2000","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib11","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1136\/ard.2010.146191","article-title":"Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis","volume":"70","author":"Hinks","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1136\/ard.2007.075895","article-title":"Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis","volume":"67","author":"C\u00e9spedes-Cruz","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.jbspin.2005.03.006","article-title":"Improvements in growth parameters in children with juvenile idiopathic arthritis associated with the effect of methotrexate on disease activity","volume":"72","author":"Ch\u00e9deville","year":"2005","journal-title":"Joint Bone Spine"},{"key":"10.1016\/j.jpeds.2013.10.029_bib14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0022-3476(98)70231-8","article-title":"Radiologic progression in patients with juvenile chronic arthritis treated with methotrexate","volume":"133","author":"Ravelli","year":"1998","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2013.10.029_bib15","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3899\/jrheum.120753","article-title":"Methotrexate and injectable tumor necrosis factor-\u03b1 inhibitor adherence and persistence in children with rheumatic diseases","volume":"40","author":"Ringold","year":"2013","journal-title":"J Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib16","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jama.2010.375","article-title":"Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial","volume":"303","author":"Foell","year":"2010","journal-title":"JAMA"},{"key":"10.1016\/j.jpeds.2013.10.029_bib17","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1056\/NEJMoa0706290","article-title":"Adalimumab with or without methotrexate in juvenile rheumatoid arthritis","volume":"359","author":"Lovell","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jpeds.2013.10.029_bib18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000081784","article-title":"Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis","volume":"219","author":"Puchta","year":"2005","journal-title":"Opthalmologica"},{"key":"10.1016\/j.jpeds.2013.10.029_bib19","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.ophtha.2009.04.020","article-title":"Methotrexate for ocular inflammatory diseases","volume":"116","author":"Gangaputra","year":"2009","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jpeds.2013.10.029_bib20","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ajo.2007.06.030","article-title":"Risk factors for the development of cataract requiring surgery in uveitis associated with juvenile idiopathic arthritis","volume":"144","author":"Sijssens","year":"2007","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib21","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ajo.2010.08.021","article-title":"Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis","volume":"151","author":"Ayuso","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib22","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.jpeds.2013.03.047","article-title":"Methotrexate therapy may prevent the onset of uveitis in juvenile idiopathic arthritis","volume":"163","author":"Papadopoulou","year":"2013","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2013.10.029_bib23","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jaad.2009.06.048","article-title":"Efficacy and safety of treatments for childhood psoriasis: a systematic literature review","volume":"62","author":"de Jager","year":"2010","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib24","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1525-1470.2008.00629.x","article-title":"Systemic methotrexate treatment in childhood psoriasis: further experience in 24 children from India","volume":"25","author":"Kaur","year":"2008","journal-title":"Pediatr Dermatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib25","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2230.2008.02907.x","article-title":"Methotrexate treatment in 13 children with severe plaque psoriasis","volume":"34","author":"Collin","year":"2009","journal-title":"Clin Exp Dermatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/ibd.21152","article-title":"Natural history of Crohn's disease: comparison between childhood- and adult-onset disease","volume":"16","author":"Pigneur","year":"2010","journal-title":"Inflamm Bowel Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib27","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1111\/j.1572-0241.2007.01474.x","article-title":"Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease","volume":"102","author":"Turner","year":"2007","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib28","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1097\/01.mib.0000235103.47280.bb","article-title":"Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study","volume":"12","author":"Uhlen","year":"2006","journal-title":"Inflamm Bowel Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib29","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1002\/art.27511","article-title":"Tumor necrosis factor alpha blockers and malignancy in children: 48 cases reported to the Food and Drug Administration","volume":"62","author":"Diak","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2036.2011.04925.x","article-title":"Efficacy and tolerability of methotrexate therapy for refractory Crohn's disease: a large single-centre experience","volume":"35","author":"Suares","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.jpeds.2013.10.029_bib31","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1002\/art.21378","article-title":"The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids","volume":"52","author":"Ramanan","year":"2005","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib32","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1067\/mjd.2002.122196","article-title":"Aggressive management of juvenile dermatomyositis results in improved outcome and decreased incidence of calcinosis","volume":"47","author":"Fisler","year":"2002","journal-title":"J Am Acad Dermatol"},{"issue":"Suppl 3","key":"10.1016\/j.jpeds.2013.10.029_bib33","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/annrheumdis-2013-eular.264","article-title":"A randomized trial in a new onset juvenile dermatomyositis: prednisone vs prednisone plus cyclosporine versus prednisone plus methotrexate","volume":"72","author":"Ruperto","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0022-3476(00)90056-8","article-title":"Methotrexate and corticosteroid therapy for pediatric localized scleroderma","volume":"136","author":"Uziel","year":"2000","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2013.10.029_bib35","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/j.1365-2133.2006.07497.x","article-title":"Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children","volume":"155","author":"Weibel","year":"2006","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib36","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/art.30264","article-title":"Methotrexate treatment in juvenile localized scleroderma: a randomized, double-blind, placebo-controlled trial","volume":"63","author":"Zulian","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib37","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.jaad.2012.03.036","article-title":"A long-term follow-up study of methotrexate in juvenile localized scleroderma (morphea)","volume":"67","author":"Zulian","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib38","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1002\/art.24876","article-title":"Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood","volume":"60","author":"Cabral","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib39","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/S0022-3476(96)70128-2","article-title":"Methotrexate treatment of Wegener granulomatosis in children","volume":"129","author":"Gottlieb","year":"1996","journal-title":"J Pediatr"},{"key":"10.1016\/j.jpeds.2013.10.029_bib40","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.3899\/jrheum.120299","article-title":"Do adult disease severity subclassifications predict use of cyclophosphamide in children with ANCA-associated vasculitis? An analysis of ARChiVe study treatment decisions","volume":"39","author":"Morishita","year":"2012","journal-title":"J Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib41","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1172\/JCI116884","article-title":"The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in\u00a0vivo model of inflammation","volume":"92","author":"Cronstein","year":"1993","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jpeds.2013.10.029_bib42","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.3899\/jrheum.111593","article-title":"ABCB1 and ABCC3 Gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis","volume":"30","author":"de Rotte","year":"2012","journal-title":"J Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib43","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/FPC.0b013e32833f2cd0","article-title":"Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype","volume":"20","author":"Moncrieffe","year":"2010","journal-title":"Pharmacogenet Genomics"},{"key":"10.1016\/j.jpeds.2013.10.029_bib44","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1136\/annrheumdis-2011-200942","article-title":"Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis","volume":"71","author":"Bulatovic","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jpeds.2013.10.029_bib45","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/art.30080","article-title":"The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response","volume":"63","author":"Becker","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib46","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/rheumatology\/ket152","article-title":"A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8\/14 protein","volume":"52","author":"Moncrieffe","year":"2013","journal-title":"Rheumatology (Oxford)"},{"key":"10.1016\/j.jpeds.2013.10.029_bib47","first-page":"2342","article-title":"Pharmacokinetics of oral methotrexate in children","volume":"43","author":"Balis","year":"1983","journal-title":"Cancer Res"},{"key":"10.1016\/j.jpeds.2013.10.029_bib48","first-page":"2230","article-title":"The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis: a controlled study","volume":"24","author":"Hunt","year":"1997","journal-title":"J Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib49","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/art.30367","article-title":"High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score","volume":"63","author":"Bulatovi\u0107","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib50","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/MPG.0b013e31822855e7","article-title":"Short-course ondansetron for the prevention of methotrexate-induced nausea in children with Crohn's disease","volume":"53","author":"Kempinska","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2013.10.029_bib51","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/art.1780401218","article-title":"The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis","volume":"40","author":"Hashkes","year":"1997","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.jpeds.2013.10.029_bib52","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.3899\/jrheum.090482","article-title":"Monitoring methotrexate toxicity in juvenile idiopathic arthritis","volume":"36","author":"Kocharla","year":"2009","journal-title":"J Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s003930200025","article-title":"Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy","volume":"61","author":"Schmeling","year":"2002","journal-title":"Z Rheumatol"},{"key":"10.1016\/j.jpeds.2013.10.029_bib54","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1001\/jama.2013.6768","article-title":"Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial","volume":"309","author":"Heijstek","year":"2013","journal-title":"JAMA"},{"key":"10.1016\/j.jpeds.2013.10.029_bib55","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/art.34348","article-title":"Rates of malignancy associated with juvenile idiopathic arthritis and its treatment","volume":"64","author":"Beukelman","year":"2012","journal-title":"Arthritis Rheum"}],"container-title":["The Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347613012791?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347613012791?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T11:01:31Z","timestamp":1647514891000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022347613012791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["S0022347613012791"],"URL":"https:\/\/doi.org\/10.1016\/j.jpeds.2013.10.029","relation":{},"ISSN":["0022-3476"],"issn-type":[{"value":"0022-3476","type":"print"}],"subject":[],"published":{"date-parts":[[2014,2]]}}}