Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis
Identifieur interne : 000408 ( Istex/Corpus ); précédent : 000407; suivant : 000409Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis
Auteurs : Carlos D. Rose ; Bernhard H. Singsen ; Andrew H. Eichenfield ; Donald P. Goldsmith ; Balu H. AthreyaSource :
- The Journal of Pediatrics [ 0022-3476 ] ; 1990.
English descriptors
- Teeft :
- Adverse reactions, American college, Arthritis, Arthritis rheum, Articular, Articular count, Articular index, Corticosteroid, Corticosteroid dependency, Corticosteroid doses, Disease activity, Dos, Dupont institute, Erosive disease, Functional class, Hemoglobin level, Hemoglobin levels, Hydroxychloroquine, Indicator variables, Initial response, Injectable, Injectable gold, Intolerable corticosteroid, Intolerable corticosteroid side effects, Joint counts, Limited range, Liver biopsies, Liver fibrosis, Lower dose, Macrophage function, Major side effects, Medication, Methotrexate, Methotrexate therapy, Methotrexate toxicity, Morning stiffness, Pediatric rheumatologists, Pediatrics october, Platelet, Platelet count, Platelet counts, Polyarticular, Polyarticular disease, Polyarticular onset, Preliminary data, Rash, Recent evaluation, Rheum, Rheumatoid, Rheumatoid arthritis, Rheumatoid arthritis patients, Rheumatology, Rheumatology services, Seashore house, Severe leukopenia, Side effects, Stiffness, Swollen joints, Systemic, Systemic polyarticular, Systemic symptoms, Therapy, Total number, Toxic effects, Toxic reaction, Toxicity, Unacceptable side effects.
Abstract
Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or d-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.
Url:
DOI: 10.1016/S0022-3476(05)80709-7
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ISTEX:0DB5EF5C3CCCF17E6F80F920E541AE1221635422Le document en format XML
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Rose</name><affiliation><mods:affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprint requests: Carlos D. Rose, MD, Division of Rheumatology, Alfred I. duPont Institute, 1600 Rockland Rd., Wilmington DE 19899.</mods:affiliation></affiliation></author><author><name sortKey="Singsen, Bernhard H" sort="Singsen, Bernhard H" uniqKey="Singsen B" first="Bernhard H." last="Singsen">Bernhard H. Singsen</name><affiliation><mods:affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</mods:affiliation></affiliation></author><author><name sortKey="Eichenfield, Andrew H" sort="Eichenfield, Andrew H" uniqKey="Eichenfield A" first="Andrew H." last="Eichenfield">Andrew H. Eichenfield</name><affiliation><mods:affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</mods:affiliation></affiliation></author><author><name sortKey="Goldsmith, Donald P" sort="Goldsmith, Donald P" uniqKey="Goldsmith D" first="Donald P." last="Goldsmith">Donald P. Goldsmith</name><affiliation><mods:affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</mods:affiliation></affiliation></author><author><name sortKey="Athreya, Balu H" sort="Athreya, Balu H" uniqKey="Athreya B" first="Balu H." last="Athreya">Balu H. Athreya</name><affiliation><mods:affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">The Journal of Pediatrics</title><title level="j" type="abbrev">YMPD</title><idno type="ISSN">0022-3476</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1990">1990</date><biblScope unit="volume">117</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="653">653</biblScope><biblScope unit="page" to="659">659</biblScope></imprint><idno type="ISSN">0022-3476</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adverse reactions</term><term>American college</term><term>Arthritis</term><term>Arthritis rheum</term><term>Articular</term><term>Articular count</term><term>Articular index</term><term>Corticosteroid</term><term>Corticosteroid dependency</term><term>Corticosteroid doses</term><term>Disease activity</term><term>Dos</term><term>Dupont institute</term><term>Erosive disease</term><term>Functional class</term><term>Hemoglobin level</term><term>Hemoglobin levels</term><term>Hydroxychloroquine</term><term>Indicator variables</term><term>Initial response</term><term>Injectable</term><term>Injectable gold</term><term>Intolerable corticosteroid</term><term>Intolerable corticosteroid side effects</term><term>Joint counts</term><term>Limited range</term><term>Liver biopsies</term><term>Liver fibrosis</term><term>Lower dose</term><term>Macrophage function</term><term>Major side effects</term><term>Medication</term><term>Methotrexate</term><term>Methotrexate therapy</term><term>Methotrexate toxicity</term><term>Morning stiffness</term><term>Pediatric rheumatologists</term><term>Pediatrics october</term><term>Platelet</term><term>Platelet count</term><term>Platelet counts</term><term>Polyarticular</term><term>Polyarticular disease</term><term>Polyarticular onset</term><term>Preliminary data</term><term>Rash</term><term>Recent evaluation</term><term>Rheum</term><term>Rheumatoid</term><term>Rheumatoid arthritis</term><term>Rheumatoid arthritis patients</term><term>Rheumatology</term><term>Rheumatology services</term><term>Seashore house</term><term>Severe leukopenia</term><term>Side effects</term><term>Stiffness</term><term>Swollen joints</term><term>Systemic</term><term>Systemic polyarticular</term><term>Systemic symptoms</term><term>Therapy</term><term>Total number</term><term>Toxic effects</term><term>Toxic reaction</term><term>Toxicity</term><term>Unacceptable side effects</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or d-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>methotrexate</json:string><json:string>rheumatoid</json:string><json:string>rheumatoid arthritis</json:string><json:string>toxicity</json:string><json:string>arthritis rheum</json:string><json:string>polyarticular</json:string><json:string>corticosteroid</json:string><json:string>articular</json:string><json:string>injectable</json:string><json:string>morning stiffness</json:string><json:string>arthritis</json:string><json:string>hydroxychloroquine</json:string><json:string>methotrexate therapy</json:string><json:string>toxic effects</json:string><json:string>rheum</json:string><json:string>rheumatology</json:string><json:string>platelet</json:string><json:string>dos</json:string><json:string>functional class</json:string><json:string>rash</json:string><json:string>stiffness</json:string><json:string>platelet counts</json:string><json:string>swollen joints</json:string><json:string>disease activity</json:string><json:string>systemic symptoms</json:string><json:string>injectable gold</json:string><json:string>major side effects</json:string><json:string>articular count</json:string><json:string>side effects</json:string><json:string>total number</json:string><json:string>dupont institute</json:string><json:string>pediatrics october</json:string><json:string>medication</json:string><json:string>systemic</json:string><json:string>intolerable corticosteroid side effects</json:string><json:string>corticosteroid dependency</json:string><json:string>joint counts</json:string><json:string>hemoglobin level</json:string><json:string>severe leukopenia</json:string><json:string>indicator variables</json:string><json:string>american college</json:string><json:string>rheumatology services</json:string><json:string>articular index</json:string><json:string>platelet count</json:string><json:string>methotrexate toxicity</json:string><json:string>liver biopsies</json:string><json:string>unacceptable side effects</json:string><json:string>initial response</json:string><json:string>hemoglobin levels</json:string><json:string>seashore house</json:string><json:string>toxic reaction</json:string><json:string>recent evaluation</json:string><json:string>systemic polyarticular</json:string><json:string>polyarticular disease</json:string><json:string>polyarticular onset</json:string><json:string>limited range</json:string><json:string>corticosteroid doses</json:string><json:string>erosive disease</json:string><json:string>lower dose</json:string><json:string>macrophage function</json:string><json:string>intolerable corticosteroid</json:string><json:string>liver fibrosis</json:string><json:string>pediatric rheumatologists</json:string><json:string>preliminary data</json:string><json:string>adverse reactions</json:string><json:string>rheumatoid arthritis patients</json:string><json:string>therapy</json:string></teeft></keywords><author><json:item><name>Carlos D. Rose MD</name><affiliations><json:string>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</json:string><json:string>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</json:string><json:string>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</json:string><json:string>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</json:string><json:string>Reprint requests: Carlos D. Rose, MD, Division of Rheumatology, Alfred I. duPont Institute, 1600 Rockland Rd., Wilmington DE 19899.</json:string></affiliations></json:item><json:item><name>Bernhard H. Singsen MD</name><affiliations><json:string>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</json:string><json:string>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</json:string><json:string>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</json:string><json:string>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</json:string></affiliations></json:item><json:item><name>Andrew H. Eichenfield MD</name><affiliations><json:string>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</json:string><json:string>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</json:string><json:string>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</json:string><json:string>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</json:string></affiliations></json:item><json:item><name>Donald P. Goldsmith MD</name><affiliations><json:string>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</json:string><json:string>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</json:string><json:string>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</json:string><json:string>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</json:string></affiliations></json:item><json:item><name>Balu H. Athreya MD</name><affiliations><json:string>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</json:string><json:string>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</json:string><json:string>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</json:string><json:string>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Pediatric pharmacology and therapeutic</value></json:item></subject><articleId><json:string>80709</json:string></articleId><arkIstex>ark:/67375/6H6-C94069RC-Z</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or d-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.</abstract><qualityIndicators><score>9.369</score><pdfWordCount>4369</pdfWordCount><pdfCharCount>27117</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>561.28 x 770.28 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>263</abstractWordCount><abstractCharCount>1865</abstractCharCount><keywordCount>1</keywordCount></qualityIndicators><title>Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</title><pmid><json:string>2213397</json:string></pmid><pii><json:string>S0022-3476(05)80709-7</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>The Journal of Pediatrics</title><language><json:string>unknown</json:string></language><publicationDate>1990</publicationDate><issn><json:string>0022-3476</json:string></issn><pii><json:string>S0022-3476(05)X8682-6</json:string></pii><volume>117</volume><issue>4</issue><pages><first>653</first><last>659</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1987, 1988, and 1989</json:string><json:string>1997</json:string><json:string>9/25/22887</json:string><json:string>1990</json:string></date><geogName></geogName><orgName><json:string>Children's Hospital of Philadelphia, Philadelphia, Pennsylvania</json:string><json:string>Institute, Wilmington, Delaware</json:string><json:string>Division of Rheumatology</json:string><json:string>Institute, Wilmington, Del</json:string><json:string>American College of Rheumatology</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Bernhard H. Singsen</json:string><json:string>Carlos D. Rose</json:string><json:string>Seashore House</json:string><json:string>Gail Mcllvain-Simpson</json:string><json:string>Patricia Rettig</json:string><json:string>Robert A. Doughty</json:string><json:string>P. Goldsmith</json:string><json:string>I. Evidence</json:string><json:string>H. Eichenfield</json:string><json:string>Published</json:string></persName><placeName><json:string>Toxicity</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Kremer et al.</json:string><json:string>Wallace et al.</json:string><json:string>Gispen et al.</json:string><json:string>Rose et al.</json:string><json:string>Steinbrocker et al.</json:string><json:string>Danao et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-C94069RC-Z</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - pediatrics</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - pediatrics</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Pediatrics, Perinatology, and Child Health</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1990</publicationDate><copyrightDate>1997</copyrightDate><doi><json:string>10.1016/S0022-3476(05)80709-7</json:string></doi><id>0DB5EF5C3CCCF17E6F80F920E541AE1221635422</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-C94069RC-Z/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-C94069RC-Z/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-C94069RC-Z/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>elsevier</p></licence></availability><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M"></p><date>1997</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</title><author xml:id="author-0000"><persName><forename type="first">Carlos D.</forename><surname>Rose</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><affiliation>Reprint requests: Carlos D. Rose, MD, Division of Rheumatology, Alfred I. duPont Institute, 1600 Rockland Rd., Wilmington DE 19899.</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Bernhard H.</forename><surname>Singsen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Andrew H.</forename><surname>Eichenfield</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Donald P.</forename><surname>Goldsmith</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Balu H.</forename><surname>Athreya</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation></author><idno type="istex">0DB5EF5C3CCCF17E6F80F920E541AE1221635422</idno><idno type="ark">ark:/67375/6H6-C94069RC-Z</idno><idno type="DOI">10.1016/S0022-3476(05)80709-7</idno><idno type="PII">S0022-3476(05)80709-7</idno><idno type="article-id">80709</idno></analytic><monogr><title level="j">The Journal of Pediatrics</title><title level="j" type="abbrev">YMPD</title><idno type="pISSN">0022-3476</idno><idno type="PII">S0022-3476(05)X8682-6</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1990"></date><biblScope unit="volume">117</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="653">653</biblScope><biblScope unit="page" to="659">659</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1997</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or d-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.</p></abstract><textClass><keywords scheme="keyword"><list><head>article-category</head><item><term>Pediatric pharmacology and therapeutic</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1990">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-C94069RC-Z/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" </istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"></istex:docType><istex:document><article version="5.0" xml:lang="en" docsubtype="fla"><item-info><jid>YMPD</jid><aid>80709</aid><ce:pii>S0022-3476(05)80709-7</ce:pii><ce:doi>10.1016/S0022-3476(05)80709-7</ce:doi><ce:copyright type="unknown" year="1997"></ce:copyright><ce:doctopics><ce:doctopic><ce:text>Pediatric pharmacology and therapeutic</ce:text></ce:doctopic></ce:doctopics></item-info><head><ce:title>Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</ce:title><ce:author-group><ce:author><ce:degrees>MD</ce:degrees><ce:given-name>Carlos D.</ce:given-name><ce:surname>Rose</ce:surname><ce:cross-ref refid="aff1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="aff3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup>d</ce:sup></ce:cross-ref><ce:cross-ref refid="cor1"><ce:sup>1</ce:sup></ce:cross-ref></ce:author><ce:author><ce:degrees>MD</ce:degrees><ce:given-name>Bernhard H.</ce:given-name><ce:surname>Singsen</ce:surname><ce:cross-ref refid="aff1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="aff3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:degrees>MD</ce:degrees><ce:given-name>Andrew H.</ce:given-name><ce:surname>Eichenfield</ce:surname><ce:cross-ref refid="aff1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="aff3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:degrees>MD</ce:degrees><ce:given-name>Donald P.</ce:given-name><ce:surname>Goldsmith</ce:surname><ce:cross-ref refid="aff1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="aff3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:degrees>MD</ce:degrees><ce:given-name>Balu H.</ce:given-name><ce:surname>Athreya</ce:surname><ce:cross-ref refid="aff1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="aff3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="aff1"><ce:label>a</ce:label><ce:textfn>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</ce:textfn></ce:affiliation><ce:affiliation id="aff2"><ce:label>b</ce:label><ce:textfn>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</ce:textfn></ce:affiliation><ce:affiliation id="aff3"><ce:label>c</ce:label><ce:textfn>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</ce:textfn></ce:affiliation><ce:affiliation id="aff4"><ce:label>d</ce:label><ce:textfn>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</ce:textfn></ce:affiliation><ce:correspondence id="cor1"><ce:label>1</ce:label><ce:text>Reprint requests: Carlos D. Rose, MD, Division of Rheumatology, Alfred I. duPont Institute, 1600 Rockland Rd., Wilmington DE 19899.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="13" month="2" year="1990"></ce:date-received><ce:date-accepted day="4" month="6" year="1990"></ce:date-accepted><ce:abstract id="ab1" class="author" xml:lang="en"><ce:abstract-sec><ce:simple-para id="SP0005">Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m<ce:sup loc="post">2</ce:sup>/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or <ce:small-caps>d</ce:small-caps>-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.</ce:simple-para></ce:abstract-sec></ce:abstract></head><tail><ce:bibliography id="R0005"><ce:section-title>References</ce:section-title><ce:bibliography-sec id="RS0005"><ce:bib-reference id="bib1"><ce:label>1.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Rosenberg</ce:surname><ce:given-name>AM</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Advanced drug therapy for juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Pediatr</sb:maintitle></sb:title><sb:volume-nr>114</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>171</sb:first-page><sb:last-page>178</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib2"><ce:label>2.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Baker</ce:surname><ce:given-name>GL</ce:given-name></sb:author><sb:author><ce:surname>Kahl</ce:surname><ce:given-name>LE</ce:given-name></sb:author><sb:author><ce:surname>Zee</ce:surname><ce:given-name>BC</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Malignancy following treatment with cyclophosphamide</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Am J Med</sb:maintitle></sb:title><sb:volume-nr>83</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>1</sb:first-page><sb:last-page>9</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib3"><ce:label>3.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Berk</ce:surname><ce:given-name>PD</ce:given-name></sb:author><sb:author><ce:surname>Goldberg</ce:surname><ce:given-name>JD</ce:given-name></sb:author><sb:author><ce:surname>Silverstein</ce:surname><ce:given-name>MN</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>304</sb:volume-nr></sb:series><sb:date>1981</sb:date></sb:issue><sb:pages><sb:first-page>441</sb:first-page><sb:last-page>447</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib4"><ce:label>4.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Kvien</ce:surname><ce:given-name>TK</ce:given-name></sb:author><sb:author><ce:surname>Hoyeraal</ce:surname><ce:given-name>HM</ce:given-name></sb:author><sb:author><ce:surname>Standstad</ce:surname><ce:given-name>B</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Azathioprine versus placebo in patients with juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>13</sb:volume-nr></sb:series><sb:date>1986</sb:date></sb:issue><sb:pages><sb:first-page>118</sb:first-page><sb:last-page>123</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib5"><ce:label>5.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Weinblatt</ce:surname><ce:given-name>ME</ce:given-name></sb:author><sb:author><ce:surname>Coblyn</ce:surname><ce:given-name>JS</ce:given-name></sb:author><sb:author><ce:surname>Fox</ce:surname><ce:given-name>DA</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Efficacy of low-dose methotrexate in rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>312</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>818</sb:first-page><sb:last-page>822</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib6"><ce:label>6.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Williams</ce:surname><ce:given-name>JH</ce:given-name></sb:author><sb:author><ce:surname>Wikens</ce:surname><ce:given-name>RF</ce:given-name></sb:author><sb:author><ce:surname>Samuelson</ce:surname><ce:given-name>CO</ce:given-name><ce:suffix>Jr.</ce:suffix></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>28</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>721</sb:first-page><sb:last-page>730</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib7"><ce:label>7.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Suarez-Almazor</ce:surname><ce:given-name>ME</ce:given-name></sb:author><sb:author><ce:surname>Fitzgerald</ce:surname><ce:given-name>A</ce:given-name></sb:author><sb:author><ce:surname>Grace</ce:surname><ce:given-name>M</ce:given-name></sb:author><sb:author><ce:surname>Russel</ce:surname><ce:given-name>AS</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>A randomized, controlled trial of parenteral methotrexate compared with sodium aurothiomalate (Myochrysine) in the treatment of rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>15</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>753</sb:first-page><sb:last-page>756</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib8"><ce:label>8.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Hamdy</ce:surname><ce:given-name>H</ce:given-name></sb:author><sb:author><ce:surname>McKendry</ce:surname><ce:given-name>RJR</ce:given-name></sb:author><sb:author><ce:surname>Mierins</ce:surname><ce:given-name>E</ce:given-name></sb:author><sb:author><ce:surname>Liver</ce:surname><ce:given-name>JA</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Low-dose methotrexate compared with azthioprine in the treatment of rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>30</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>361</sb:first-page><sb:last-page>368</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib9"><ce:label>9.</ce:label><sb:reference><sb:comment>[Abstract]</sb:comment><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Giannini</ce:surname><ce:given-name>EH</ce:given-name></sb:author><sb:author><ce:surname>Brewer</ce:surname><ce:given-name>EJ</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate in the treatment of recalcitrant JRA: results of the double-blind, placebo (P) controlled, randomized trial</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>S82</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib10"><ce:label>10.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Wallace</ce:surname><ce:given-name>CA</ce:given-name></sb:author><sb:author><ce:surname>Bleyer</ce:surname><ce:given-name>WA</ce:given-name></sb:author><sb:author><ce:surname>Sherry</ce:surname><ce:given-name>DD</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>677</sb:first-page><sb:last-page>681</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib11"><ce:label>11.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Brewer</ce:surname><ce:given-name>EJ</ce:given-name></sb:author><sb:author><ce:surname>Bass</ce:surname><ce:given-name>J</ce:given-name></sb:author><sb:author><ce:surname>Baum</ce:surname><ce:given-name>J</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Current proposed revision of JRA criteria</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>20</sb:volume-nr></sb:series><sb:date>1977</sb:date></sb:issue><sb:pages><sb:first-page>195</sb:first-page><sb:last-page>199</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib12"><ce:label>12.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Steinbrocker</ce:surname><ce:given-name>O</ce:given-name></sb:author><sb:author><ce:surname>Traeger</ce:surname><ce:given-name>CN</ce:given-name></sb:author><sb:author><ce:surname>Batterman</ce:surname><ce:given-name>RC</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Therapeutic criteria in rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>JAMA</sb:maintitle></sb:title><sb:volume-nr>140</sb:volume-nr></sb:series><sb:date>1949</sb:date></sb:issue><sb:pages><sb:first-page>659</sb:first-page><sb:last-page>662</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib13"><ce:label>13.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Gispen</ce:surname><ce:given-name>JG</ce:given-name></sb:author><sb:author><ce:surname>Alarcon</ce:surname><ce:given-name>GS</ce:given-name></sb:author><sb:author><ce:surname>Johnson</ce:surname><ce:given-name>JJ</ce:given-name></sb:author><sb:author><ce:surname>Acton</ce:surname><ce:given-name>RT</ce:given-name></sb:author><sb:author><ce:surname>Barger</ce:surname><ce:given-name>BO</ce:given-name></sb:author><sb:author><ce:surname>Koopman</ce:surname><ce:given-name>WJ</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Toxicity to methotrexate in rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>14</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>74</sb:first-page><sb:last-page>79</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib14"><ce:label>14.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Klippel</ce:surname><ce:given-name>JH</ce:given-name></sb:author><sb:author><ce:surname>Decker</ce:surname><ce:given-name>JL</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate in rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>312</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>853</sb:first-page><sb:last-page>854</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib15"><ce:label>15.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Kremer</ce:surname><ce:given-name>JM</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate therapy in the treatment of rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Rheum Dis Clin North Am</sb:maintitle></sb:title><sb:volume-nr>15</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>533</sb:first-page><sb:last-page>556</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib16"><ce:label>16.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Olsen</ce:surname><ce:given-name>NJ</ce:given-name></sb:author><sb:author><ce:surname>Murray</ce:surname><ce:given-name>LM</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Antiproliferative effects of methotrexate on peripheral blood mononuclear cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>378</sb:first-page><sb:last-page>385</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib17"><ce:label>17.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Hu</ce:surname><ce:given-name>S</ce:given-name></sb:author><sb:author><ce:surname>Mitcho</ce:surname><ce:given-name>YL</ce:given-name></sb:author><sb:author><ce:surname>Oronsky</ce:surname><ce:given-name>AL</ce:given-name></sb:author><sb:author><ce:surname>Kerwar</ce:surname><ce:given-name>SS</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Studies on the effect of methotrexate on macrophage function</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>15</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>206</sb:first-page><sb:last-page>209</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib18"><ce:label>18.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Gubner</ce:surname><ce:given-name>R</ce:given-name></sb:author><sb:author><ce:surname>August</ce:surname><ce:given-name>S</ce:given-name></sb:author><sb:author><ce:surname>Ginsberg</ce:surname><ce:given-name>V</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Therapeutic supression of tissue reactivity: effects of aminoptrerin in rheumatoid arthritis and psoriasis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Am J Med Sci</sb:maintitle></sb:title><sb:volume-nr>221</sb:volume-nr></sb:series><sb:date>1951</sb:date></sb:issue><sb:pages><sb:first-page>176</sb:first-page><sb:last-page>184</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib19"><ce:label>19.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Bjorkman</ce:surname><ce:given-name>DJ</ce:given-name></sb:author><sb:author><ce:surname>Hammond</ce:surname><ce:given-name>EH</ce:given-name></sb:author><sb:author><ce:surname>Randall</ce:surname><ce:given-name>GL</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>31</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>1465</sb:first-page><sb:last-page>1471</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib20"><ce:label>20.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Aponte</ce:surname><ce:given-name>J</ce:given-name></sb:author><sb:author><ce:surname>Petrelli</ce:surname><ce:given-name>M</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Histopathologic findings in the liver of rheumatoid arthritis patients treated with long-term bolus methotrexate</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>31</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>1457</sb:first-page><sb:last-page>1462</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib21"><ce:label>21.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Kremer</ce:surname><ce:given-name>JM</ce:given-name></sb:author><sb:author><ce:surname>Lee</ce:surname><ce:given-name>RG</ce:given-name></sb:author><sb:author><ce:surname>Tolman</ce:surname><ce:given-name>KG</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>121</sb:first-page><sb:last-page>127</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib22"><ce:label>22.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Rau</ce:surname><ce:given-name>R</ce:given-name></sb:author><sb:author><ce:surname>Karger</ce:surname><ce:given-name>T</ce:given-name></sb:author><sb:author><ce:surname>Herborn</ce:surname><ce:given-name>G</ce:given-name></sb:author><sb:author><ce:surname>Frenzel</ce:surname><ce:given-name>H</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment with methotrexate</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>16</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>489</sb:first-page><sb:last-page>493</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib23"><ce:label>23.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Wilkens</ce:surname><ce:given-name>RJ</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Reappraisal of the use of methotrexate in rheumatic disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Am J Med</sb:maintitle></sb:title><sb:volume-nr>75</sb:volume-nr></sb:series><sb:date>1983</sb:date></sb:issue><sb:pages><sb:first-page>19</sb:first-page><sb:last-page>25</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib24"><ce:label>24.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Alarcon</ce:surname><ce:given-name>GS</ce:given-name></sb:author><sb:author><ce:surname>Tracy</ce:surname><ce:given-name>IC</ce:given-name></sb:author><sb:author><ce:surname>Blackburn</ce:surname><ce:given-name>WD</ce:given-name><ce:suffix>Jr</ce:suffix></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate in rheumatoid arthritis: toxic effects as the major factor limiting long-term treatment</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>671</sb:first-page><sb:last-page>676</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib25"><ce:label>25.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Segal</ce:surname><ce:given-name>R</ce:given-name></sb:author><sb:author><ce:surname>Caspi</ce:surname><ce:given-name>D</ce:given-name></sb:author><sb:author><ce:surname>Tishler</ce:surname><ce:given-name>M</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Short-term effects of low dose methotrexate on the acute phase reaction in patients with rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Rheumatol</sb:maintitle></sb:title><sb:volume-nr>16</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>914</sb:first-page><sb:last-page>917</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib26"><ce:label>26.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Truckenbrodt</ce:surname><ce:given-name>H</ce:given-name></sb:author><sb:author><ce:surname>Hafner</ce:surname><ce:given-name>R</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate therapy in juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>29</sb:volume-nr></sb:series><sb:date>1986</sb:date></sb:issue><sb:pages><sb:first-page>801</sb:first-page><sb:last-page>807</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib27"><ce:label>27.</ce:label><sb:reference><sb:comment>[Abstract]</sb:comment><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Danao</ce:surname><ce:given-name>T</ce:given-name></sb:author><sb:author><ce:surname>Steinbrunner</ce:surname><ce:given-name>J</ce:given-name></sb:author><sb:author><ce:surname>Medendorp</ce:surname><ce:given-name>S</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Methotrexate in juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>S28</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib28"><ce:label>28.</ce:label><sb:reference><sb:comment>[Abstract]</sb:comment><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Rose</ce:surname><ce:given-name>CD</ce:given-name></sb:author><sb:author><ce:surname>Eichenfield</ce:surname><ce:given-name>AH</ce:given-name></sb:author><sb:author><ce:surname>Goldsmith</ce:surname><ce:given-name>DP</ce:given-name></sb:author><sb:author><ce:surname>Athreya</ce:surname><ce:given-name>BH</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Safety and efficacy of methotrexate therapy in juvenile rheumatoid arthritis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>S28</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib29"><ce:label>29.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Kremer</ce:surname><ce:given-name>JM</ce:given-name></sb:author><sb:author><ce:surname>Galivan</ce:surname><ce:given-name>J</ce:given-name></sb:author><sb:author><ce:surname>Streckfuss</ce:surname><ce:given-name>A</ce:given-name></sb:author><sb:author><ce:surname>Kamen</ce:surname><ce:given-name>B</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate metabolism: analysis in blood and liver of rheumatoid arthritis patients—association with hepatic folate deficiency and formation of polyglutamates</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Arthritis Rheum</sb:maintitle></sb:title><sb:volume-nr>29</sb:volume-nr></sb:series><sb:date>1986</sb:date></sb:issue><sb:pages><sb:first-page>832</sb:first-page><sb:last-page>835</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib30"><ce:label>30.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Nordstrom</ce:surname><ce:given-name>DM</ce:given-name></sb:author><sb:author><ce:surname>West</ce:surname><ce:given-name>SG</ce:given-name></sb:author><sb:author><ce:surname>Andersen</ce:surname><ce:given-name>PA</ce:given-name></sb:author><sb:author><ce:surname>Sharp</ce:surname><ce:given-name>JT</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Pulse methotrexate therapy in rheumatoid arthritis: a controlled prospective roentgenographic study</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann Intern Med</sb:maintitle></sb:title><sb:volume-nr>107</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>797</sb:first-page><sb:last-page>801</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib31"><ce:label>31.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Tugwell</ce:surname><ce:given-name>P</ce:given-name></sb:author><sb:author><ce:surname>Bennet</ce:surname><ce:given-name>K</ce:given-name></sb:author><sb:author><ce:surname>Gent</ce:surname><ce:given-name>M</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Methotrexate in rheumatoid arthritis: indications, contraindications, efficacy and safety</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann Intern Med</sb:maintitle></sb:title><sb:volume-nr>107</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>358</sb:first-page><sb:last-page>366</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib32"><ce:label>32.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Mullarkey</ce:surname><ce:given-name>M</ce:given-name></sb:author><sb:author><ce:surname>Blumenstein</ce:surname><ce:given-name>B</ce:given-name></sb:author><sb:author><ce:surname>Andrade</ce:surname><ce:given-name>P</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Methotrexate in the treatment of corticosteroid dependent asthma: a double-blind, crossover study</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>318</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>603</sb:first-page><sb:last-page>607</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib33"><ce:label>33.</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Kozarek</ce:surname><ce:given-name>RA</ce:given-name></sb:author><sb:author><ce:surname>Patterson</ce:surname><ce:given-name>DJ</ce:given-name></sb:author><sb:author><ce:surname>Martin</ce:surname><ce:given-name>MD</ce:given-name></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann Intern Med</sb:maintitle></sb:title><sb:volume-nr>110</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>353</sb:first-page><sb:last-page>356</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis</title></titleInfo><name type="personal"><namePart type="given">Carlos D.</namePart><namePart type="family">Rose</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><affiliation>Reprint requests: Carlos D. Rose, MD, Division of Rheumatology, Alfred I. duPont Institute, 1600 Rockland Rd., Wilmington DE 19899.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernhard H.</namePart><namePart type="family">Singsen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrew H.</namePart><namePart type="family">Eichenfield</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald P.</namePart><namePart type="family">Goldsmith</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Balu H.</namePart><namePart type="family">Athreya</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatrics, University of Pennsylvania School of Medicine, USA</affiliation><affiliation>Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, USA</affiliation><affiliation>Division of Rheumatology, the Children's Seashore House at Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA</affiliation><affiliation>Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1990</dateIssued><copyrightDate encoding="w3cdtf">1997</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or d-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.</abstract><subject><genre>article-category</genre><topic>Pediatric pharmacology and therapeutic</topic></subject><relatedItem type="host"><titleInfo><title>The Journal of Pediatrics</title></titleInfo><titleInfo type="abbreviated"><title>YMPD</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1990</dateIssued></originInfo><identifier type="ISSN">0022-3476</identifier><identifier type="PII">S0022-3476(05)X8682-6</identifier><part><date>1990</date><detail type="volume"><number>117</number><caption>vol.</caption></detail><detail type="issue"><number>4</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1A</start><end>26A</end></extent><extent unit="issue-pages"><start>515</start><end>676</end></extent><extent unit="issue-pages"><start>27A</start><end>50A</end></extent><extent unit="pages"><start>653</start><end>659</end></extent></part></relatedItem><identifier type="istex">0DB5EF5C3CCCF17E6F80F920E541AE1221635422</identifier><identifier type="ark">ark:/67375/6H6-C94069RC-Z</identifier><identifier type="DOI">10.1016/S0022-3476(05)80709-7</identifier><identifier type="PII">S0022-3476(05)80709-7</identifier><identifier type="ArticleID">80709</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-C94069RC-Z/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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