How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

Taylor, Peter C; Balsa, A.; Ab, Mongey; Avouac, Jérôme; Marotte, Hubert; Rb, Mueller

doi:10.3390/jcm8040515

Cited by 58 publications

(47 citation statements)

References 165 publications

(260 reference statements)

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“…Based on its efficacy, safety, large dose-titratable range, options for either an oral or parenteral route of administration, and cost-effectiveness, methotrexate holds a unique place in the management of RA. 12 Recommended practice is to treat to a target of remission or low disease activity, as assessed by composite scores of disease activity, and to titrate therapy according to response. 13 However, many patients with established RA do not achieve treatment targets with methotrexate monotherapy which may also have issues with gastrointestinal tolerability.…”

Section: Pharmacological Managementmentioning

confidence: 99%

Update on the diagnosis and management of early rheumatoid arthritis

Taylor

2020

Clinical Medicine

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Section: Pharmacological Managementmentioning

confidence: 99%

Update on the diagnosis and management of early rheumatoid arthritis

Taylor

2020

Clinical Medicine

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“…In this direction, the T2T strategy is the ideal approach. T2T therapy comprises fine principles: (a) the definition of a treatment target, (b) close monitoring and follow-up at predefined times to assess disease activity using composite measures, (c) regular treatment adjustment if the target is not achieved within a scheduled time, (d) consideration of patients’ individualized aspects, and (e) the shared decision making with the patient [14,33,34]. MTX is considered the “anchor”-drug among the csDMARDs.…”

Section: Treatment Strategiesmentioning

confidence: 99%

Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations for Low Unmet Needs?

Drosos

2019

JCM

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Despite the significant progress in Rheumatoid Arthritis (RA) therapeutics, there are several reports in the literature claiming that the size of unmet needs in RA is large. In the era before biologics, there was indeed a significant number of patients who did not achieve low disease activity (LDA) or disease remission due to limited therapeutic choices in the doctors’ armamentarium. Treatment wise, great progress has been achieved over the last decades with the discovery and introduction in therapeutics of new molecules, such as the biological (b) disease-modifying anti-rheumatic drugs (DMARDs), and the targeted synthetic (ts) DMARDs. Today, with such a plethora of conventional synthetic (cs) DMARDs, tsDMARDs, and bDMARDs, why are we unable to successfully treat RA patients? What is wrong? However, a new drug for RA does not mean it is necessary to switch to a new treatment. It is very easy to change and switch therapies when the patient complains about pain and stiffness. In this setting, it is obligatory to rule out other comorbidities and disorders that may be the cause of the pain first. Thus, clinicians must have a deep knowledge of the drug therapy and be able to adjust the treatment when needed. A minute clinical examination must be carried out on every visit with close monitoring of the patient. A treat-to-target (T2T) approach and the application of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) recommendations and strategies should minimize the unmet needs.

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“…The actual mechanism by which methotrexate exerts its anti-rheumatoid arthritis action still remains unclear [3]. Nevertheless, methotrexate is used in the treatment of rheumatoid arthritis [4]. On the other hand, methotrexate inhibits thymidylate synthase (TS) enzyme.…”

Section: Introductionmentioning

confidence: 99%

Identification of a putative anti-rheumatoid arthritis molecule by virtual screening

Shakil¹,

Abuzenadah²,

Attar³

et al. 2020

Trop. J. Pharm Res

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Purpose: To propose an improved chemical skeleton whose scaffolds could be used for the design of future thymidylate synthase (TS)-inhibitors against rheumatoid arthritis. Methods: The drug discovery platform, ‘MCULE’, was employed for inhibitor-screening. The ‘methotrexate-interaction site’ in the crystal (PDB ID 5X66) was used as a target. One ‘RO5 violation’ was permitted. A maximum of ‘10 rotatable bonds’ and ‘100 diverse molecules’ were also allowed in the protocol. The ‘threshold similarity cut off’ was 0.7. The input values describing the remaining parameters were kept as ‘default’. The ‘Open Babel Linear Fingerprint’ was used for the analyses of molecular descriptors, followed by ADME-check. Results: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidine corresponding to the MCULE ID-7590816301-0-93 exhibited the overall best binding with TS. The free energy of binding was -8.6 kcal/mol. A total of 17 amino acid residues were significant for the binding interactions. Importantly, 9 residues were common to methotrexate binding. It satisfied pertinent ADME conditions. Conclusion: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidinemay emerge as a potent seed molecule for TS-inhibitor design in the context of rheumatoid arthritis. It has satisfied pertinent ADME features. However, there is need for further wet laboratory validation. Keywords: Anti-rheumatoid arthritis, Inhibitor design, Methotrexate, Seed molecule, Thymidylate synthase, Virtual screening

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How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

Cited by 58 publications

References 165 publications

Update on the diagnosis and management of early rheumatoid arthritis

Update on the diagnosis and management of early rheumatoid arthritis

Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations for Low Unmet Needs?

Identification of a putative anti-rheumatoid arthritis molecule by virtual screening

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