Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group
Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. 358 patients were randomly assigned leflunomide (100 mg d...
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| Veröffentlicht in: | The Lancet (British edition) 1999-01, Vol.353 (9149), p.259 |
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| creator | Smolen, J S Kalden, J R Scott, D L Rozman, B Kvien, T K Larsen, A Loew-Friedrich, I Oed, C Rosenburg, R |
| description | Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis.
358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat.
The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p |
| format | Article |
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358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat.
The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group.
Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.</description><identifier>ISSN: 0140-6736</identifier><identifier>PMID: 9929017</identifier><language>eng</language><publisher>England</publisher><subject>Algorithms ; Analysis of Variance ; Antirheumatic Agents - therapeutic use ; Arthritis, Rheumatoid - diagnostic imaging ; Arthritis, Rheumatoid - drug therapy ; Disease Progression ; Double-Blind Method ; Female ; Humans ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - therapeutic use ; Isoxazoles - adverse effects ; Isoxazoles - therapeutic use ; Leflunomide ; Male ; Middle Aged ; Placebos ; Radiography ; Statistics, Nonparametric ; Sulfasalazine - therapeutic use ; Treatment Outcome</subject><ispartof>The Lancet (British edition), 1999-01, Vol.353 (9149), p.259</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9929017$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smolen, J S</creatorcontrib><creatorcontrib>Kalden, J R</creatorcontrib><creatorcontrib>Scott, D L</creatorcontrib><creatorcontrib>Rozman, B</creatorcontrib><creatorcontrib>Kvien, T K</creatorcontrib><creatorcontrib>Larsen, A</creatorcontrib><creatorcontrib>Loew-Friedrich, I</creatorcontrib><creatorcontrib>Oed, C</creatorcontrib><creatorcontrib>Rosenburg, R</creatorcontrib><title>Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis.
358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat.
The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group.
Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.</description><subject>Algorithms</subject><subject>Analysis of Variance</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis, Rheumatoid - diagnostic imaging</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Disease Progression</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Isoxazoles - adverse effects</subject><subject>Isoxazoles - therapeutic use</subject><subject>Leflunomide</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Placebos</subject><subject>Radiography</subject><subject>Statistics, Nonparametric</subject><subject>Sulfasalazine - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0140-6736</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1OwzAUhLMAlVI4AtI7AEFOnF92qCotUiUWdF-92M-KkRNbjg0KV-NyVGoXrGYWo29Gc5UsWVawtKp5dZPcTtMnY6yoWLlIFm2btyyrl8nvRiktUMyAo4QJFYUZrAJDysTRDloSCDs49CThW4cenEFBnT3no3E9TmjwR48EegQUQX8R-J7igMFqCehD73XQ0zMgSBs7Q2ln9CgfwZ8Yp4qJTn6IJmhBY_AEwWs0T7CJ3jrCEfb_xnyEKGfYehvdXXKt0Ex0f9FVcnjdHNa7dP--fVu_7FNX8jqtiHdU5YXkTauaMpdEeU6iKUtGXV2XiFkhEJs6y1gmFMdOFm2hsG5bVDxjfJU8nLEudgPJo_N6QD8fLx_yPzckchk</recordid><startdate>19990123</startdate><enddate>19990123</enddate><creator>Smolen, J S</creator><creator>Kalden, J R</creator><creator>Scott, D L</creator><creator>Rozman, B</creator><creator>Kvien, T K</creator><creator>Larsen, A</creator><creator>Loew-Friedrich, I</creator><creator>Oed, C</creator><creator>Rosenburg, R</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19990123</creationdate><title>Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group</title><author>Smolen, J S ; Kalden, J R ; Scott, D L ; Rozman, B ; Kvien, T K ; Larsen, A ; Loew-Friedrich, I ; Oed, C ; Rosenburg, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p537-6e3be624d389f852dee22ec8550eb775aa14caa871101cf3abd494fa799af3103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Algorithms</topic><topic>Analysis of Variance</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>Arthritis, Rheumatoid - diagnostic imaging</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Disease Progression</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Isoxazoles - adverse effects</topic><topic>Isoxazoles - therapeutic use</topic><topic>Leflunomide</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Placebos</topic><topic>Radiography</topic><topic>Statistics, Nonparametric</topic><topic>Sulfasalazine - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smolen, J S</creatorcontrib><creatorcontrib>Kalden, J R</creatorcontrib><creatorcontrib>Scott, D L</creatorcontrib><creatorcontrib>Rozman, B</creatorcontrib><creatorcontrib>Kvien, T K</creatorcontrib><creatorcontrib>Larsen, A</creatorcontrib><creatorcontrib>Loew-Friedrich, I</creatorcontrib><creatorcontrib>Oed, C</creatorcontrib><creatorcontrib>Rosenburg, R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smolen, J S</au><au>Kalden, J R</au><au>Scott, D L</au><au>Rozman, B</au><au>Kvien, T K</au><au>Larsen, A</au><au>Loew-Friedrich, I</au><au>Oed, C</au><au>Rosenburg, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>1999-01-23</date><risdate>1999</risdate><volume>353</volume><issue>9149</issue><spage>259</spage><pages>259-</pages><issn>0140-6736</issn><abstract>Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis.
358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat.
The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group.
Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.</abstract><cop>England</cop><pmid>9929017</pmid></addata></record> |
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| ispartof | The Lancet (British edition), 1999-01, Vol.353 (9149), p.259 |
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| subjects | Algorithms Analysis of Variance Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - diagnostic imaging Arthritis, Rheumatoid - drug therapy Disease Progression Double-Blind Method Female Humans Immunosuppressive Agents - adverse effects Immunosuppressive Agents - therapeutic use Isoxazoles - adverse effects Isoxazoles - therapeutic use Leflunomide Male Middle Aged Placebos Radiography Statistics, Nonparametric Sulfasalazine - therapeutic use Treatment Outcome |
| title | Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group |
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