The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy
Objective To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA). Methods Methotrexate (MTX)–naive patients (in the Golimumab Before Employing Methotrexate as the First‐Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO‐BEFORE...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-05, Vol.63 (5), p.1200-1210 |
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| creator | Emery, Paul Fleischmann, Roy van der Heijde, Désirée Keystone, Edward C. Genovese, Mark C. Conaghan, Philip G. Hsia, Elizabeth C. Xu, Weichun Baratelle, Anna Beutler, Anna Rahman, Mahboob U. |
| description | Objective
To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA).
Methods
Methotrexate (MTX)–naive patients (in the Golimumab Before Employing Methotrexate as the First‐Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO‐BEFORE] study; n = 637) and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO‐FORWARD] study; n = 444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab or placebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO‐BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO‐FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score.
Results
In the GO‐BEFORE study, the mean ± SD changes in the modified Sharp score from baseline to week 52 (control period) were 1.4 ± 4.6 in group 1, 1.3 ± 6.2 in group 2 (P = 0.266), 0.7 ± 5.2 in group 3 (P = 0.015), and 0.1 ± 1.8 in group 4 (P = 0.025). In the GO‐FORWARD study, changes from baseline to week 24 (control period) were 0.6 ± 2.4 in group 1, 0.3 ± 1.6 in group 2 (P = 0.361), 0.6 ± 2.7 in group 3 (P = 0.953), and 0.2 ± 1.3 in group 4 (P = 0.293).
Conclusion
Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO‐BEFORE study. Radiographic progression in the GO‐FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study. |
| doi_str_mv | 10.1002/art.30263 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1517048676</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3277865811</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4483-fb7c64bb4eb0eaa5565c608f189bbafc5f4828fd4f8a39b7c44f3538a494df953</originalsourceid><addsrcrecordid>eNp1kV1rFDEUhoModq1e-AckIL3wYtpkksxmvCvFLygIZb0eksxJJ2VmsyYZdPsL_VmeOqstolc54Ty8D7yHkJecnXLG6jOTyqlgdSMekRVXdVsxLvhjsmKMyUqolh-RZznf4LcWSjwlRzUXTKlarsiPzQAUvAdXMo2eXscxTPNkLI1bmkwf4nUyuyE4uks4Qs4BFwF3AyBWYugp6ocUSshv6RXkeVySktn2cQq30FMXtyXFccQxl7kP8JfKgo8J6ARliCXBd1OAlgFQvKeY8oA0vkD6J_icPPFmzPDi8B6TL-_fbS4-VpefP3y6OL-snJRaVN6uXSOtlWAZGKNUo1zDtOe6tdZ4p7zUtfa99NqIFmEpPXamjWxl71sljsnrJRf7-DpDLt1NnNMWlR1XfM2kbtYNUm8WyqWYcwLf7VKYTNp3nHV3N-uwtO7XzZB9dUic7QT9H_L3kRA4OQAmOzN6bNaFfM_Jmuu1uAs6W7hvYYT9_43d-dVmUf8EWGq0Ug</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1517048676</pqid></control><display><type>article</type><title>The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Emery, Paul ; Fleischmann, Roy ; van der Heijde, Désirée ; Keystone, Edward C. ; Genovese, Mark C. ; Conaghan, Philip G. ; Hsia, Elizabeth C. ; Xu, Weichun ; Baratelle, Anna ; Beutler, Anna ; Rahman, Mahboob U.</creator><creatorcontrib>Emery, Paul ; Fleischmann, Roy ; van der Heijde, Désirée ; Keystone, Edward C. ; Genovese, Mark C. ; Conaghan, Philip G. ; Hsia, Elizabeth C. ; Xu, Weichun ; Baratelle, Anna ; Beutler, Anna ; Rahman, Mahboob U.</creatorcontrib><description>Objective
To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA).
Methods
Methotrexate (MTX)–naive patients (in the Golimumab Before Employing Methotrexate as the First‐Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO‐BEFORE] study; n = 637) and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO‐FORWARD] study; n = 444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab or placebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO‐BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO‐FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score.
Results
In the GO‐BEFORE study, the mean ± SD changes in the modified Sharp score from baseline to week 52 (control period) were 1.4 ± 4.6 in group 1, 1.3 ± 6.2 in group 2 (P = 0.266), 0.7 ± 5.2 in group 3 (P = 0.015), and 0.1 ± 1.8 in group 4 (P = 0.025). In the GO‐FORWARD study, changes from baseline to week 24 (control period) were 0.6 ± 2.4 in group 1, 0.3 ± 1.6 in group 2 (P = 0.361), 0.6 ± 2.7 in group 3 (P = 0.953), and 0.2 ± 1.3 in group 4 (P = 0.293).
Conclusion
Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO‐BEFORE study. Radiographic progression in the GO‐FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study.</description><identifier>ISSN: 0004-3591</identifier><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 1529-0131</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.30263</identifier><identifier>PMID: 21305524</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Antibodies, Monoclonal - therapeutic use ; Antirheumatic Agents - therapeutic use ; Arthritis, Rheumatoid - diagnostic imaging ; Arthritis, Rheumatoid - drug therapy ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Disease Progression ; Diseases of the osteoarticular system ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Humans ; Immunomodulators ; Inflammatory joint diseases ; Intention to Treat Analysis ; Male ; Medical sciences ; Methotrexate - therapeutic use ; Middle Aged ; Pharmacology. Drug treatments ; Radiography ; Remission Induction ; Treatment Outcome</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2011-05, Vol.63 (5), p.1200-1210</ispartof><rights>Copyright © 2011 by the American College of Rheumatology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4483-fb7c64bb4eb0eaa5565c608f189bbafc5f4828fd4f8a39b7c44f3538a494df953</citedby><cites>FETCH-LOGICAL-c4483-fb7c64bb4eb0eaa5565c608f189bbafc5f4828fd4f8a39b7c44f3538a494df953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.30263$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.30263$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24218733$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21305524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Fleischmann, Roy</creatorcontrib><creatorcontrib>van der Heijde, Désirée</creatorcontrib><creatorcontrib>Keystone, Edward C.</creatorcontrib><creatorcontrib>Genovese, Mark C.</creatorcontrib><creatorcontrib>Conaghan, Philip G.</creatorcontrib><creatorcontrib>Hsia, Elizabeth C.</creatorcontrib><creatorcontrib>Xu, Weichun</creatorcontrib><creatorcontrib>Baratelle, Anna</creatorcontrib><creatorcontrib>Beutler, Anna</creatorcontrib><creatorcontrib>Rahman, Mahboob U.</creatorcontrib><title>The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheum</addtitle><description>Objective
To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA).
Methods
Methotrexate (MTX)–naive patients (in the Golimumab Before Employing Methotrexate as the First‐Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO‐BEFORE] study; n = 637) and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO‐FORWARD] study; n = 444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab or placebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO‐BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO‐FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score.
Results
In the GO‐BEFORE study, the mean ± SD changes in the modified Sharp score from baseline to week 52 (control period) were 1.4 ± 4.6 in group 1, 1.3 ± 6.2 in group 2 (P = 0.266), 0.7 ± 5.2 in group 3 (P = 0.015), and 0.1 ± 1.8 in group 4 (P = 0.025). In the GO‐FORWARD study, changes from baseline to week 24 (control period) were 0.6 ± 2.4 in group 1, 0.3 ± 1.6 in group 2 (P = 0.361), 0.6 ± 2.7 in group 3 (P = 0.953), and 0.2 ± 1.3 in group 4 (P = 0.293).
Conclusion
Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO‐BEFORE study. Radiographic progression in the GO‐FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study.</description><subject>Adult</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis, Rheumatoid - diagnostic imaging</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Disease Progression</subject><subject>Diseases of the osteoarticular system</subject><subject>Drug Administration Schedule</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Inflammatory joint diseases</subject><subject>Intention to Treat Analysis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methotrexate - therapeutic use</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Radiography</subject><subject>Remission Induction</subject><subject>Treatment Outcome</subject><issn>0004-3591</issn><issn>2326-5191</issn><issn>1529-0131</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1rFDEUhoModq1e-AckIL3wYtpkksxmvCvFLygIZb0eksxJJ2VmsyYZdPsL_VmeOqstolc54Ty8D7yHkJecnXLG6jOTyqlgdSMekRVXdVsxLvhjsmKMyUqolh-RZznf4LcWSjwlRzUXTKlarsiPzQAUvAdXMo2eXscxTPNkLI1bmkwf4nUyuyE4uks4Qs4BFwF3AyBWYugp6ocUSshv6RXkeVySktn2cQq30FMXtyXFccQxl7kP8JfKgo8J6ARliCXBd1OAlgFQvKeY8oA0vkD6J_icPPFmzPDi8B6TL-_fbS4-VpefP3y6OL-snJRaVN6uXSOtlWAZGKNUo1zDtOe6tdZ4p7zUtfa99NqIFmEpPXamjWxl71sljsnrJRf7-DpDLt1NnNMWlR1XfM2kbtYNUm8WyqWYcwLf7VKYTNp3nHV3N-uwtO7XzZB9dUic7QT9H_L3kRA4OQAmOzN6bNaFfM_Jmuu1uAs6W7hvYYT9_43d-dVmUf8EWGq0Ug</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Emery, Paul</creator><creator>Fleischmann, Roy</creator><creator>van der Heijde, Désirée</creator><creator>Keystone, Edward C.</creator><creator>Genovese, Mark C.</creator><creator>Conaghan, Philip G.</creator><creator>Hsia, Elizabeth C.</creator><creator>Xu, Weichun</creator><creator>Baratelle, Anna</creator><creator>Beutler, Anna</creator><creator>Rahman, Mahboob U.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201105</creationdate><title>The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy</title><author>Emery, Paul ; Fleischmann, Roy ; van der Heijde, Désirée ; Keystone, Edward C. ; Genovese, Mark C. ; Conaghan, Philip G. ; Hsia, Elizabeth C. ; Xu, Weichun ; Baratelle, Anna ; Beutler, Anna ; Rahman, Mahboob U.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4483-fb7c64bb4eb0eaa5565c608f189bbafc5f4828fd4f8a39b7c44f3538a494df953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>Arthritis, Rheumatoid - diagnostic imaging</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Disease Progression</topic><topic>Diseases of the osteoarticular system</topic><topic>Drug Administration Schedule</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Inflammatory joint diseases</topic><topic>Intention to Treat Analysis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methotrexate - therapeutic use</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Radiography</topic><topic>Remission Induction</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Fleischmann, Roy</creatorcontrib><creatorcontrib>van der Heijde, Désirée</creatorcontrib><creatorcontrib>Keystone, Edward C.</creatorcontrib><creatorcontrib>Genovese, Mark C.</creatorcontrib><creatorcontrib>Conaghan, Philip G.</creatorcontrib><creatorcontrib>Hsia, Elizabeth C.</creatorcontrib><creatorcontrib>Xu, Weichun</creatorcontrib><creatorcontrib>Baratelle, Anna</creatorcontrib><creatorcontrib>Beutler, Anna</creatorcontrib><creatorcontrib>Rahman, Mahboob U.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Emery, Paul</au><au>Fleischmann, Roy</au><au>van der Heijde, Désirée</au><au>Keystone, Edward C.</au><au>Genovese, Mark C.</au><au>Conaghan, Philip G.</au><au>Hsia, Elizabeth C.</au><au>Xu, Weichun</au><au>Baratelle, Anna</au><au>Beutler, Anna</au><au>Rahman, Mahboob U.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheum</addtitle><date>2011-05</date><risdate>2011</risdate><volume>63</volume><issue>5</issue><spage>1200</spage><epage>1210</epage><pages>1200-1210</pages><issn>0004-3591</issn><issn>2326-5191</issn><eissn>1529-0131</eissn><eissn>2326-5205</eissn><coden>ARHEAW</coden><abstract>Objective
To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA).
Methods
Methotrexate (MTX)–naive patients (in the Golimumab Before Employing Methotrexate as the First‐Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO‐BEFORE] study; n = 637) and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO‐FORWARD] study; n = 444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab or placebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO‐BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO‐FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score.
Results
In the GO‐BEFORE study, the mean ± SD changes in the modified Sharp score from baseline to week 52 (control period) were 1.4 ± 4.6 in group 1, 1.3 ± 6.2 in group 2 (P = 0.266), 0.7 ± 5.2 in group 3 (P = 0.015), and 0.1 ± 1.8 in group 4 (P = 0.025). In the GO‐FORWARD study, changes from baseline to week 24 (control period) were 0.6 ± 2.4 in group 1, 0.3 ± 1.6 in group 2 (P = 0.361), 0.6 ± 2.7 in group 3 (P = 0.953), and 0.2 ± 1.3 in group 4 (P = 0.293).
Conclusion
Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO‐BEFORE study. Radiographic progression in the GO‐FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21305524</pmid><doi>10.1002/art.30263</doi><tpages>11</tpages></addata></record> |
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| ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2011-05, Vol.63 (5), p.1200-1210 |
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| subjects | Adult Antibodies, Monoclonal - therapeutic use Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - diagnostic imaging Arthritis, Rheumatoid - drug therapy Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Disease Progression Diseases of the osteoarticular system Drug Administration Schedule Drug Therapy, Combination Female Humans Immunomodulators Inflammatory joint diseases Intention to Treat Analysis Male Medical sciences Methotrexate - therapeutic use Middle Aged Pharmacology. Drug treatments Radiography Remission Induction Treatment Outcome |
| title | The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy |
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