Skip to main content
Erschienen in: Inflammopharmacology 5/2020

05.08.2020 | Review

The advances of methotrexate resistance in rheumatoid arthritis

verfasst von: Jun Yu, Peng Zhou

Erschienen in: Inflammopharmacology | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is characterized by a chronic fluctuating course and immune dysfunction, resulting in affecting the health and life quality of RA patients. Methotrexate (MTX), as the standard gold treatment of RA, has received more and more clinical applications and basic pharmacological research. In several observational studies, MTXR, and treatment responses in RA patients show that the ratio of MTXR and non- response is about 30%–50%, namely MTX resistance (MTXR). Extensive efforts have been made into the investigation of the mechanism and effective biomarkers in MTXR of RA. In this paper, we discuss the recent findings regarding the critical signaling pathways of MTXR in RA. Provide research targets and directions for a drug therapy that develop preventive strategies and effective treatments of MTXR.
Literatur
Zurück zum Zitat Association CR (2018) 2018 Chinese guideline for the diagnosis and treatment of rheumatoid arthritis. Chin J Intern Med 57:242–251 Association CR (2018) 2018 Chinese guideline for the diagnosis and treatment of rheumatoid arthritis. Chin J Intern Med 57:242–251
Zurück zum Zitat Braun J et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthr Rheum 58:73–81. https://doi.org/10.1002/art.23144CrossRef Braun J et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthr Rheum 58:73–81. https://​doi.​org/​10.​1002/​art.​23144CrossRef
Zurück zum Zitat Bunni M, Doig MT, Donato H, Kesavan V, Priest DG (1988) Role of methylenetetrahydrofolate depletion in methotrexate-mediated intracellular thymidylate synthesis inhibition in cultured L1210 cells. Cancer Res 48:3398–3404PubMed Bunni M, Doig MT, Donato H, Kesavan V, Priest DG (1988) Role of methylenetetrahydrofolate depletion in methotrexate-mediated intracellular thymidylate synthesis inhibition in cultured L1210 cells. Cancer Res 48:3398–3404PubMed
Zurück zum Zitat Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J (2004) Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 50:2766–2774. https://doi.org/10.1002/art.20460CrossRefPubMed Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J (2004) Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 50:2766–2774. https://​doi.​org/​10.​1002/​art.​20460CrossRefPubMed
Zurück zum Zitat Lampropoulos CE et al (2015) Adverse events and infections in patients with rheumatoid arthritis treated with conventional drugs or biologic agents: a real world study. Clin Exp Rheumatol 33:216–224PubMed Lampropoulos CE et al (2015) Adverse events and infections in patients with rheumatoid arthritis treated with conventional drugs or biologic agents: a real world study. Clin Exp Rheumatol 33:216–224PubMed
Zurück zum Zitat Leclerc GJ, Mou C, Leclerc GM, Mian AM, Barredo JC (2010) Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy. Leukemia 24:552–562. https://doi.org/10.1038/leu.2009.282CrossRefPubMed Leclerc GJ, Mou C, Leclerc GM, Mian AM, Barredo JC (2010) Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy. Leukemia 24:552–562. https://​doi.​org/​10.​1038/​leu.​2009.​282CrossRefPubMed
Zurück zum Zitat Marotte H, Arnaud B, Diasparra J, Zrioual S, Miossec P (2008) Association between the level of circulating bioactive tumor necrosis factor alpha and the tumor necrosis factor alpha gene polymorphism at -308 in patients with rheumatoid arthritis treated with a tumor necrosis factor alpha inhibitor. Arthritis Rheum 58:1258–1263. https://doi.org/10.1002/art.23430CrossRefPubMed Marotte H, Arnaud B, Diasparra J, Zrioual S, Miossec P (2008) Association between the level of circulating bioactive tumor necrosis factor alpha and the tumor necrosis factor alpha gene polymorphism at -308 in patients with rheumatoid arthritis treated with a tumor necrosis factor alpha inhibitor. Arthritis Rheum 58:1258–1263. https://​doi.​org/​10.​1002/​art.​23430CrossRefPubMed
Zurück zum Zitat Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernandez P, Cronstein BN (2007) The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5′-nucleotidase: findings in a study of ecto-5′-nucleotidase gene-deficient mice. Arthritis Rheum 56:1440–1445. https://doi.org/10.1002/art.22643CrossRefPubMed Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernandez P, Cronstein BN (2007) The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5′-nucleotidase: findings in a study of ecto-5′-nucleotidase gene-deficient mice. Arthritis Rheum 56:1440–1445. https://​doi.​org/​10.​1002/​art.​22643CrossRefPubMed
Zurück zum Zitat Pachot A et al (2007) Increased tumor necrosis factor-alpha mRNA expression in whole blood from patients with rheumatoid arthritis: reduction after infliximab treatment does not predict response. J Rheumatol 34:2158–2161PubMed Pachot A et al (2007) Increased tumor necrosis factor-alpha mRNA expression in whole blood from patients with rheumatoid arthritis: reduction after infliximab treatment does not predict response. J Rheumatol 34:2158–2161PubMed
Zurück zum Zitat Sergeant JC et al. (2018) Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS) Arthritis Res Ther 20:147 https://doi.org/10.1186/s13075-018-1645-5 Sergeant JC et al. (2018) Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS) Arthritis Res Ther 20:147 https://​doi.​org/​10.​1186/​s13075-018-1645-5
Zurück zum Zitat Sun W et al (2019) Correlations between the polymorphism of +869T/C in TGF-β1 and rheumatoid arthritis. J Musculoskelet Neuronal Interact 19:127–132PubMedPubMedCentral Sun W et al (2019) Correlations between the polymorphism of +869T/C in TGF-β1 and rheumatoid arthritis. J Musculoskelet Neuronal Interact 19:127–132PubMedPubMedCentral
Zurück zum Zitat Tengstrand B, Ahlmen M, Hafstrom I (2004) The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years. J Rheumatol 31:214–222PubMed Tengstrand B, Ahlmen M, Hafstrom I (2004) The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years. J Rheumatol 31:214–222PubMed
Zurück zum Zitat van Hamburg JP et al (2011) Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum 63:73–83. https://doi.org/10.1002/art.30093CrossRefPubMed van Hamburg JP et al (2011) Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum 63:73–83. https://​doi.​org/​10.​1002/​art.​30093CrossRefPubMed
Zurück zum Zitat Varani K, Massara A, Vincenzi F, Tosi A, Padovan M, Trotta F, Borea PA (2009) Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti-tumor necrosis factor alpha but not methotrexate. Arthritis Rheum 60:2880–2891. https://doi.org/10.1002/art.24794CrossRefPubMed Varani K, Massara A, Vincenzi F, Tosi A, Padovan M, Trotta F, Borea PA (2009) Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti-tumor necrosis factor alpha but not methotrexate. Arthritis Rheum 60:2880–2891. https://​doi.​org/​10.​1002/​art.​24794CrossRefPubMed
Zurück zum Zitat Varani K, Padovan M, Vincenzi F, Targa M, Trotta F, Govoni M, Borea PA (2011) A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res Ther 13:R197. https://doi.org/10.1186/ar3527CrossRefPubMedPubMedCentral Varani K, Padovan M, Vincenzi F, Targa M, Trotta F, Govoni M, Borea PA (2011) A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res Ther 13:R197. https://​doi.​org/​10.​1186/​ar3527CrossRefPubMedPubMedCentral
Zurück zum Zitat Volk EL, Rohde K, Rhee M, McGuire JJ, Doyle LA, Ross DD, Schneider E (2000) Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res 60:3514–3521PubMed Volk EL, Rohde K, Rhee M, McGuire JJ, Doyle LA, Ross DD, Schneider E (2000) Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res 60:3514–3521PubMed
Zurück zum Zitat Wei W (2016) Soft regulation of inflammatory immune response. Chin Pharmacol Bull 32:297–303 Wei W (2016) Soft regulation of inflammatory immune response. Chin Pharmacol Bull 32:297–303
Zurück zum Zitat Yao X et al (2017) Over-expression of mdr1/P-gp is associated with methotrexate resistance in patients with rheumatoid arthritis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. Chin J Cell Mol Immunol 33:815–819 Yao X et al (2017) Over-expression of mdr1/P-gp is associated with methotrexate resistance in patients with rheumatoid arthritis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. Chin J Cell Mol Immunol 33:815–819
Zurück zum Zitat Youssef P, Roth J, Frosch M, Costello P, Fitzgerald O, Sorg C, Bresnihan B (1999) Expression of myeloid related proteins (MRP) 8 and 14 and the MRP8/14 heterodimer in rheumatoid arthritis synovial membrane. J Rheumatol 26:2523–2528PubMed Youssef P, Roth J, Frosch M, Costello P, Fitzgerald O, Sorg C, Bresnihan B (1999) Expression of myeloid related proteins (MRP) 8 and 14 and the MRP8/14 heterodimer in rheumatoid arthritis synovial membrane. J Rheumatol 26:2523–2528PubMed
Metadaten
Titel
The advances of methotrexate resistance in rheumatoid arthritis
verfasst von
Jun Yu
Peng Zhou
Publikationsdatum
05.08.2020
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 5/2020
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-020-00741-3

Weitere Artikel der Ausgabe 5/2020

Inflammopharmacology 5/2020 Zur Ausgabe