How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy
Identifieur interne : 000345 ( Pmc/Curation ); précédent : 000344; suivant : 000346How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy
Auteurs : Peter. C. Taylor [Royaume-Uni] ; Alejandro Balsa Criado ; Anne-Barbara Mongey ; Jerome Avouac ; Hubert Marotte ; Rudiger B. MuellerSource :
- Journal of Clinical Medicine [ 2077-0383 ] ; 2019.
Abstract
Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.
Url:
DOI: 10.3390/jcm8040515
PubMed: 30991730
PubMed Central: 6518419
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Taylor</name><affiliation wicri:level="1"><nlm:aff id="af1-jcm-08-00515">Botnar Research Centre, NDORMS, University of Oxford, Windmill Road, Oxford OX3 7LD, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Botnar Research Centre, NDORMS, University of Oxford, Windmill Road, Oxford OX3 7LD</wicri:regionArea></affiliation></author><author><name sortKey="Balsa Criado, Alejandro" sort="Balsa Criado, Alejandro" uniqKey="Balsa Criado A" first="Alejandro" last="Balsa Criado">Alejandro Balsa Criado</name><affiliation><nlm:aff id="af2-jcm-08-00515">Rheumatology unit, University Hospital La Paz, Institute for Health Research–IdiPAZ, Universidad Autonoma de Madrid, 28046 Madrid, Spain;<email>alejandro.balsa@salud.madrid.org</email></nlm:aff></affiliation></author><author><name sortKey="Mongey, Anne Barbara" sort="Mongey, Anne Barbara" uniqKey="Mongey A" first="Anne-Barbara" last="Mongey">Anne-Barbara Mongey</name><affiliation><nlm:aff id="af3-jcm-08-00515">St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland;<email>anne.b.mongey@ucd.ie</email></nlm:aff></affiliation></author><author><name sortKey="Avouac, Jerome" sort="Avouac, Jerome" uniqKey="Avouac J" first="Jerome" last="Avouac">Jerome Avouac</name><affiliation><nlm:aff id="af4-jcm-08-00515">Paris Descartes University, Sorbonne Paris Cité, Rheumatology Department, Cochin Hopital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France;<email>javouac@me.com</email></nlm:aff></affiliation></author><author><name sortKey="Marotte, Hubert" sort="Marotte, Hubert" uniqKey="Marotte H" first="Hubert" last="Marotte">Hubert Marotte</name><affiliation><nlm:aff id="af5-jcm-08-00515">SAINBIOSE, INSERM U1059, Université de Lyon, Saint-Etienne, France Service de Rhumatologie, CHU Saint-Etienne, 42055 Saint-Etienne, France;<email>Hubert.marotte@chu-st-etienne.fr</email></nlm:aff></affiliation></author><author><name sortKey="Mueller, Rudiger B" sort="Mueller, Rudiger B" uniqKey="Mueller R" first="Rudiger B." last="Mueller">Rudiger B. Mueller</name><affiliation><nlm:aff id="af6-jcm-08-00515">Division of Rheumatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland;<email>ruediger.mueler@ksa.ch</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30991730</idno><idno type="pmc">6518419</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518419</idno><idno type="RBID">PMC:6518419</idno><idno type="doi">10.3390/jcm8040515</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000345</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000345</idno><idno type="wicri:Area/Pmc/Curation">000345</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000345</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy</title><author><name sortKey="Taylor, Peter C" sort="Taylor, Peter C" uniqKey="Taylor P" first="Peter. C." last="Taylor">Peter. C. Taylor</name><affiliation wicri:level="1"><nlm:aff id="af1-jcm-08-00515">Botnar Research Centre, NDORMS, University of Oxford, Windmill Road, Oxford OX3 7LD, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Botnar Research Centre, NDORMS, University of Oxford, Windmill Road, Oxford OX3 7LD</wicri:regionArea></affiliation></author><author><name sortKey="Balsa Criado, Alejandro" sort="Balsa Criado, Alejandro" uniqKey="Balsa Criado A" first="Alejandro" last="Balsa Criado">Alejandro Balsa Criado</name><affiliation><nlm:aff id="af2-jcm-08-00515">Rheumatology unit, University Hospital La Paz, Institute for Health Research–IdiPAZ, Universidad Autonoma de Madrid, 28046 Madrid, Spain;<email>alejandro.balsa@salud.madrid.org</email></nlm:aff></affiliation></author><author><name sortKey="Mongey, Anne Barbara" sort="Mongey, Anne Barbara" uniqKey="Mongey A" first="Anne-Barbara" last="Mongey">Anne-Barbara Mongey</name><affiliation><nlm:aff id="af3-jcm-08-00515">St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland;<email>anne.b.mongey@ucd.ie</email></nlm:aff></affiliation></author><author><name sortKey="Avouac, Jerome" sort="Avouac, Jerome" uniqKey="Avouac J" first="Jerome" last="Avouac">Jerome Avouac</name><affiliation><nlm:aff id="af4-jcm-08-00515">Paris Descartes University, Sorbonne Paris Cité, Rheumatology Department, Cochin Hopital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France;<email>javouac@me.com</email></nlm:aff></affiliation></author><author><name sortKey="Marotte, Hubert" sort="Marotte, Hubert" uniqKey="Marotte H" first="Hubert" last="Marotte">Hubert Marotte</name><affiliation><nlm:aff id="af5-jcm-08-00515">SAINBIOSE, INSERM U1059, Université de Lyon, Saint-Etienne, France Service de Rhumatologie, CHU Saint-Etienne, 42055 Saint-Etienne, France;<email>Hubert.marotte@chu-st-etienne.fr</email></nlm:aff></affiliation></author><author><name sortKey="Mueller, Rudiger B" sort="Mueller, Rudiger B" uniqKey="Mueller R" first="Rudiger B." last="Mueller">Rudiger B. Mueller</name><affiliation><nlm:aff id="af6-jcm-08-00515">Division of Rheumatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland;<email>ruediger.mueler@ksa.ch</email></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Clinical Medicine</title><idno type="eISSN">2077-0383</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Med</journal-id><journal-id journal-id-type="iso-abbrev">J Clin Med</journal-id><journal-id journal-id-type="publisher-id">jcm</journal-id><journal-title-group><journal-title>Journal of Clinical Medicine</journal-title></journal-title-group><issn pub-type="epub">2077-0383</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30991730</article-id><article-id pub-id-type="pmc">6518419</article-id><article-id pub-id-type="doi">10.3390/jcm8040515</article-id><article-id pub-id-type="publisher-id">jcm-08-00515</article-id><article-categories><subj-group subj-group-type="heading"><subject>Perspective</subject></subj-group></article-categories><title-group><article-title>How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-7766-6167</contrib-id><name><surname>Taylor</surname><given-names>Peter. C.</given-names></name><xref ref-type="aff" rid="af1-jcm-08-00515">1</xref><xref rid="c1-jcm-08-00515" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-8070-7062</contrib-id><name><surname>Balsa Criado</surname><given-names>Alejandro</given-names></name><xref ref-type="aff" rid="af2-jcm-08-00515">2</xref></contrib><contrib contrib-type="author"><name><surname>Mongey</surname><given-names>Anne-Barbara</given-names></name><xref ref-type="aff" rid="af3-jcm-08-00515">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2463-218X</contrib-id><name><surname>Avouac</surname><given-names>Jerome</given-names></name><xref ref-type="aff" rid="af4-jcm-08-00515">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-1177-9497</contrib-id><name><surname>Marotte</surname><given-names>Hubert</given-names></name><xref ref-type="aff" rid="af5-jcm-08-00515">5</xref></contrib><contrib contrib-type="author"><name><surname>Mueller</surname><given-names>Rudiger B.</given-names></name><xref ref-type="aff" rid="af6-jcm-08-00515">6</xref></contrib></contrib-group><aff id="af1-jcm-08-00515"><label>1</label>Botnar Research Centre, NDORMS, University of Oxford, Windmill Road, Oxford OX3 7LD, UK</aff><aff id="af2-jcm-08-00515"><label>2</label>Rheumatology unit, University Hospital La Paz, Institute for Health Research–IdiPAZ, Universidad Autonoma de Madrid, 28046 Madrid, Spain;<email>alejandro.balsa@salud.madrid.org</email></aff><aff id="af3-jcm-08-00515"><label>3</label>St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland;<email>anne.b.mongey@ucd.ie</email></aff><aff id="af4-jcm-08-00515"><label>4</label>Paris Descartes University, Sorbonne Paris Cité, Rheumatology Department, Cochin Hopital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France;<email>javouac@me.com</email></aff><aff id="af5-jcm-08-00515"><label>5</label>SAINBIOSE, INSERM U1059, Université de Lyon, Saint-Etienne, France Service de Rhumatologie, CHU Saint-Etienne, 42055 Saint-Etienne, France;<email>Hubert.marotte@chu-st-etienne.fr</email></aff><aff id="af6-jcm-08-00515"><label>6</label>Division of Rheumatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland;<email>ruediger.mueler@ksa.ch</email></aff><author-notes><corresp id="c1-jcm-08-00515"><label>*</label>Correspondence: <email>peter.taylor@kennedy.ox.ac.uk</email>; Tel.: +44-1865737830</corresp></author-notes><pub-date pub-type="epub"><day>15</day><month>4</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>4</month><year>2019</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>515</elocation-id><history><date date-type="received"><day>13</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>11</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.</p></abstract><kwd-group><kwd>methotrexate</kwd><kwd>rheumatoid arthritis</kwd><kwd>tolerability</kwd><kwd>efficacy</kwd><kwd>posology</kwd><kwd>titration</kwd><kwd>oral route</kwd><kwd>subcutaneous route</kwd><kwd>bioavailability</kwd><kwd>effectiveness</kwd></kwd-group></article-meta></front><floats-group><table-wrap id="jcm-08-00515-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">jcm-08-00515-t001_Table 1</object-id><label>Table 1</label><caption><p>Drug interactions. MTX, methotrexate.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Interactions</th><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Source of Interactions</th></tr></thead><tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Increase MTX levels</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Allopurinol, triamterene</p></list-item><list-item><p>Decrease renal MTX clearance: ciprofloxacin, cephalothin, penicillin, probenecid, sulfonamides</p></list-item><list-item><p>Decrease MTX excretion: diuretics, proton pump inhibitors</p></list-item><list-item><p>Increase MTX reabsorption by the kidney tubule: probenecid</p></list-item></list></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Decrease MTX levels</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Decrease intestinal absorption of MTX: chloramphenicol, tetracyclines</p></list-item></list></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Increase the risk of bone marrow suppression</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Chloramphenicol, co-trimoxazole, pyrimethamine, sulfonamides, trimethoprine-sulfamethoxazole</p></list-item></list></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Increase liver toxicity</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Alcohol, leflunomide</p></list-item></list></td></tr></tbody></table></table-wrap><table-wrap id="jcm-08-00515-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">jcm-08-00515-t002_Table 2</object-id><label>Table 2</label><caption><p>Preparation of MTX therapy.</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1">Diagnosis of rheumatoid/inflammatory arthritis and/or need for treatment</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Diagnosis of chronic kidney or liver diseases</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Assessment of cardiovascular risks</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Assessment of a neoplastic disease</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Discussion on smoking habits and the advantage of smoking cessation</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Evaluation/judging of depression and resilience/coping strategies</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Assessment of anemia, leukopenia, or thrombocytopenia</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Documentation of concomitant drug therapy</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Defining therapeutic aim</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Shared decision making with the patient</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Evaluation of alcohol-consumption </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Diagnosis of active/chronic infection with herpes zoster, tuberculosis, hepatitis, HIV, relevant fungal infection</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Diagnosis of immunodeficiency</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Documentation of vaccination status</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Consider testing for tuberculosis</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anticonception/assessing wish of conception/family planning</td></tr></tbody></table></table-wrap><table-wrap id="jcm-08-00515-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">jcm-08-00515-t003_Table 3</object-id><label>Table 3</label><caption><p>Key points patients will need to be counselled about when rheumatologists adopt a shared decision-making approach to the recommended regime. NSAIDs, non-steroidal anti-inflammatory drugs.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Topics to Discuss with Patients</th></tr></thead><tbody><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• The choice of routes of administration and the advantages of each</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Expected time to experiencing benefits (this is very important as a patient may experience transient tolerability problems such as nausea prior to experiencing and improvement in symptoms and there will therefore be a danger of non-adherence if there has not been appropriate counselling)</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Potential toxicities with reassurance about the capability to mitigate these risks through regular and appropriate blood monitoring</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• The potential tolerability issues, especially nausea with appropriate reassurance that this can be lessened or mitigated with use of folic acid supplementation or parenteral administration</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Women of childbearing potential need to be counselled about pregnancy and family planning.</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Vaccinations and how to ensure optimum outcomes of vaccination </td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Alcohol consumption</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">• Interactions between MTX and other medication with particular advice about NSAIDs</td></tr></tbody></table></table-wrap><table-wrap id="jcm-08-00515-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">jcm-08-00515-t004_Table 4</object-id><label>Table 4</label><caption><p>Key recommendations for clinical use of MTX. csDMARD, conventional synthetic disease-modifying antirheumatic drugs; bDMARDs, biological DMARDs; tsDMARDs, targeted synthetic DMARDs; SC, subcutaneous.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Key Points for Clinical Use of MTX</th></tr></thead><tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Modify predictors of response to MTX</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Encourage smoking cessation</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Limit alcohol consumption</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Ensure appropriate education on how to optimise outcomes</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Manage anxiety and depression</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Start at the right dose</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Generally 10–15 mg/week, but should be personalized<break></break> There is no need to start with higher dose</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Choose between oral and parenteral route. </td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Escalate as quickly as tolerated</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Titrate dose according to individual clinical response<break></break> Generally aim to reach a dose of at least 20 mg/week after 6 months<break></break> Consider local recommendations and clinical context</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Switch to SC route for doses higher than 15 mg/week to enhance MTX bioavailability</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Prevent side effects</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Start folic acid supplementation at a dose of at least 5 mg/week and up to 5 mg/day other than the day of methotrexate (or folinic acid at a dose lower than 7.5 mg/week)</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Instruct the patient to not take folic acid on the day of MTX administration</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Folinic acid should be administered on a weekly basis the day after MTX administration</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Counsel patients about risk mitigation through blood monitoring according to local protocols</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Be aware of potential drug to drug interactions</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Instruct the patients to seek advice from their rheumatologist about compatibility with methotrexate of self-medicated drugs or drugs prescribed by another physician</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>In case of poor tolerability</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Diminish gastrointestinal side effects by switching to SC route</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>In case of inadequate response</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Enhance MTX bioavailability by splitting oral dose or switching to SC route</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Consider combination with csDMARD, bDMARDs or tsDMARDs<break></break> Do not stop MTX nor reduce MTX dose unless there are toxicity or tolerability concerns</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Give time for MTX achieving maximum clinical benefit</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Use intra-articular or systemic glucocorticoids as bridging therapies</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> Educate the patient and adopt a shared decision-making approach</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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