How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy
Abstract
:1. Introduction
2. Pharmacology
2.1. Pharmacokinetics
2.2. Mode of Action
3. MTX: A Forefront Position among csDMARDs
3.1. Flexible
3.2. Clinically Efficient
3.3. Ancillary Benefits
3.4. Cost-Effectiveness
3.5. Combinable with Other Treatments
3.6. Challenges Associated with MTX Use
4. How to Get the Most out of MTX as a First-Line Treatment?
4.1. Dealing with Modifiable Predictors of Response to MTX
4.2. Choosing the Route of Administration
4.3. Starting at the Right Dose
4.4. Escalating and Adapting the MTX Dose
4.5. Switching to SC Route
4.6. Giving Time for MTX to Achieve its Maximum Clinical Benefit and Using Bridge Therapies
4.7. Preventing or Dealing with Adverse Events by Folic Acid Supplementation
4.8. Potential Toxicities
4.9. Placing MTX as an Anchor Drug
4.10. Conception and Pregnancy
4.11. Vaccinations
4.12. No Need for MTX Discontinuation in Case of Surgery
4.13. Sharing the Decision Making with the Patient
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Interactions | Source of Interactions |
---|---|
Increase MTX levels |
|
Decrease MTX levels |
|
Increase the risk of bone marrow suppression |
|
Increase liver toxicity |
|
Diagnosis of rheumatoid/inflammatory arthritis and/or need for treatment |
Diagnosis of chronic kidney or liver diseases |
Assessment of cardiovascular risks |
Assessment of a neoplastic disease |
Discussion on smoking habits and the advantage of smoking cessation |
Evaluation/judging of depression and resilience/coping strategies |
Assessment of anemia, leukopenia, or thrombocytopenia |
Documentation of concomitant drug therapy |
Defining therapeutic aim |
Shared decision making with the patient |
Evaluation of alcohol-consumption |
Diagnosis of active/chronic infection with herpes zoster, tuberculosis, hepatitis, HIV, relevant fungal infection |
Diagnosis of immunodeficiency |
Documentation of vaccination status |
Consider testing for tuberculosis |
Anticonception/assessing wish of conception/family planning |
Topics to Discuss with Patients |
---|
• The choice of routes of administration and the advantages of each |
• 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) |
• Potential toxicities with reassurance about the capability to mitigate these risks through regular and appropriate blood monitoring |
• 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 |
• Women of childbearing potential need to be counselled about pregnancy and family planning. |
• Vaccinations and how to ensure optimum outcomes of vaccination |
• Alcohol consumption |
• Interactions between MTX and other medication with particular advice about NSAIDs |
Key Points for Clinical Use of MTX |
---|
Modify predictors of response to MTX |
Encourage smoking cessation |
Limit alcohol consumption |
Ensure appropriate education on how to optimise outcomes |
Manage anxiety and depression |
Start at the right dose |
Generally 10–15 mg/week, but should be personalized There is no need to start with higher dose |
Choose between oral and parenteral route. |
Escalate as quickly as tolerated |
Titrate dose according to individual clinical response Generally aim to reach a dose of at least 20 mg/week after 6 months Consider local recommendations and clinical context |
Switch to SC route for doses higher than 15 mg/week to enhance MTX bioavailability |
Prevent side effects |
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) |
Instruct the patient to not take folic acid on the day of MTX administration |
Folinic acid should be administered on a weekly basis the day after MTX administration |
Counsel patients about risk mitigation through blood monitoring according to local protocols |
Be aware of potential drug to drug interactions |
Instruct the patients to seek advice from their rheumatologist about compatibility with methotrexate of self-medicated drugs or drugs prescribed by another physician |
In case of poor tolerability |
Diminish gastrointestinal side effects by switching to SC route |
In case of inadequate response |
Enhance MTX bioavailability by splitting oral dose or switching to SC route |
Consider combination with csDMARD, bDMARDs or tsDMARDs Do not stop MTX nor reduce MTX dose unless there are toxicity or tolerability concerns |
Give time for MTX achieving maximum clinical benefit |
Use intra-articular or systemic glucocorticoids as bridging therapies |
Educate the patient and adopt a shared decision-making approach |
© 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
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Taylor, P.C.; Balsa Criado, A.; Mongey, A.-B.; Avouac, J.; Marotte, H.; Mueller, R.B. How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy. J. Clin. Med. 2019, 8, 515. https://doi.org/10.3390/jcm8040515
Taylor PC, Balsa Criado A, Mongey A-B, Avouac J, Marotte H, Mueller RB. How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy. Journal of Clinical Medicine. 2019; 8(4):515. https://doi.org/10.3390/jcm8040515
Chicago/Turabian StyleTaylor, Peter. C., Alejandro Balsa Criado, Anne-Barbara Mongey, Jerome Avouac, Hubert Marotte, and Rudiger B. Mueller. 2019. "How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy" Journal of Clinical Medicine 8, no. 4: 515. https://doi.org/10.3390/jcm8040515