Current and emerging treatment options in the management of lupus

Jordan, Natasha; D’Cruz, David

doi:10.2147/itt.s40675

Cited by 35 publications

(33 citation statements)

References 136 publications

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“…Thiopurine drugs, namely azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are immunosuppressive agents that are, due to their low cost and high effectiveness, widely used in the treatment of inflammatory bowel diseases (IBD), but also in other autoimmune diseases, some hemopoetic disorders and some solid organ transplant [1][2][3][4][5]. However, the occurrence of adverse drug reactions limits the use of these drugs.…”

Section: Indroductionmentioning

confidence: 99%

Determination of thiopurine S -methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry

Pecher

Dokupilová

Zelinková

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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Determination of thiopurine S-methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry, Journal of Pharmaceutical and Biomedical Analysishttp://dx.doi.org/10. 1016/j.jpba.2017.05.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Highlights New HILIC-HPLC-MS method was developed for determination of TPMT activity  HILIC-HPLC-MS combination was approved by excellent performance parameters  HILIC-HPLC-MS was compared to traditional RP-HPLC-UV as well as advanced RP-HPLC-MS  Conventional approaches were surpassed in terms of selectivity, LOD, analysis time  HILIC-HPLC-MS is favorable for routine assay of 6-MMP/6-MP ratio in RBC lysates List of abbreviations6-MMP -6-methylmercaptopurine, 6-MP -6-mercaptopurine, 6-TG -6-thioguanine, AZA -azathioprine, Cl-P -6-chloropurine, DTT -dithiothreitol, IBD -inflammatory bowel diseases, RBC -red blood cells, SAM -S-adenosyl-L-methionine, TGN -thioguanine nucleotides, TPMT -thiopurine-S-methyl transferase. IndroductionThiopurine drugs, namely azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are immunosuppressive agents that are, due to their low cost and high effectiveness, widely used in the treatment of inflammatory bowel diseases (IBD), but also in other autoimmune diseases, some hemopoetic disorders and some solid organ transplant [1][2][3][4][5]. However, the occurrence of adverse drug reactions limits the use of these drugs. Up to 15 % of IBD patients discontinue this type of treatment due to adverse events that include nausea, skin reactions, pancreatitis, hepatotoxicity or myelotoxicity [6,7].Thiopurine drugs are prodrugs, so their biological activity is preceded by extensive metabolism. Briefly, after absorption, AZA is metabolized in the liver to 6-MP which then can be metabolized to active thioguanine nucleotides (TGN) and to inactive methylated product 6-methylmercaptopurine (6-MMP) by the thiopurine-S-methyl transferase (TPMT) enzyme [8]. TPMT (EC 2.1.1.67), a key enzyme involved in the thiopurine drug metabolism, is subject to common genetic polymorphism that leads to trimodial distribution of the TPMT activity in population [9]. Individuals with lower TPMT activity might have an increased risk of developing thiopurine-induced myelosuppression. On the contrary, individuals with high TPMT activity have lower concentrations of active TGN metabolites resulting in reduced therapeutic efficacy of the drug [10]. In addition, high TPMT activity leads to accumulation of the hepatotoxic methylated metabolites [11]. Therefore, some scientific committees advise to determine the TP...

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Section: Indroductionmentioning

confidence: 99%

Determination of thiopurine S -methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry

Pecher

Dokupilová

Zelinková

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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“…Cyclophosphamide (CTX) is one of the commonly used immunosuppressants and has been employed to treat a variety of autoimmune disorders, including but not limited to, systemic lupus erythematosus (SLE), systemic sclerosis, some forms of vasculitis, rheumatoid arthritis, and severe aplastic anemia [1]. As a nitrogen mustard prodrug, CTX undergoes hepatic conversion to form active metabolites which subsequently cause cell death by leading to inter-and intrastrand DNA crosslinking.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Enhance Pulmonary Antimicrobial Immunity and Prevent Following Bacterial Infection

Chen

Huang

et al. 2020

Stem Cells International

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Background. Immunosuppressants such as cyclophosphamide (CTX) have been employed to treat a wide array of autoimmune diseases. The most unfavourable side effects of these drugs are their suppression on the antimicrobial immunity and increasing the risk of infection. As a promising substitution/adjunct, mesenchymal stem cells (MSCs) are currently being tested in several clinical trials. However, their influence on the recipients' antimicrobial immunity remains unclear. Methods. In this study, C57BL/6 mice were treated with either CTX or MSCs, and then both the innate and adaptive immunity of the lung were determined. To investigate the influence of CTX and MSCs on the immune defence against infection, the treated mice were intranasally infected with opportunistic pathogen Haemophilus influenzae (Hi). Bacterial clearance and antibacterial immune responses were analysed. Results. Our data showed that CTX strongly inhibited the proliferation of lung immune cells, including alveolar macrophages (AMs) and T cells, whereas MSCs increased the numbers of these cells. CTX suppressed the phagocytic activity of AMs; on the contrary, MSCs enhanced it. Notably, infusion of MSCs led to a remarkable increase of regulatory T cells and Th1 cells in the lung. When infected by Hi, CTX did not significantly impair the elimination of invaded bacteria. However, MSC-treated mice exhibited accelerated bacterial clearance and moderate inflammation and tissue damage. Conclusion. Our study reported that unlike traditional immunosuppressants, modulation of MSCs on the recipient's immune response is more elegant. It could preserve and even enhance the antimicrobial defence, suggesting that MSCs are better choice for patients with high risk of infection or those who need long-term immunosuppressive regimen.

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“…While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppressant and/or biologic therapy (2). In a subgroup of patients, SLE can be severe and potentially life threatening requiring prompt management strategies.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic plasma exchange for refractory SLE: A comparison of outcomes between different sub-phenotypes

Soyuoz¹,

Karadağ²,

Karaağaç³

et al. 2018

Eur J Rheumatol

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Objective: Therapeutic plasma exchange (TPE) offers an alternative therapeutic modality for patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). However, there is conflicting evidence regarding its efficacy in different sub-phenotypes. This study aimed to investigate the main clinical characteristics and outcomes of patients with different phenotypes of SLE and APS treated with TPE at a tertiary care center. Material and Methods: The database of the Blood and Apheresis Unit between 2001 and 2013 was screened for patients with SLE and primary APS. SLE disease activity index (SELENA-SLEDAI), the indications for treatment, complications, and outcomes were obtained from a review of medical records and phone calls. A total of 24 patients (SLE: 20, APS: 4) were recruited for the study. Results: Mean ages of SLE (M/F: 1/19) and primary APS (PAPS) patients (M/F: 2/2) were 32.4±12.89 and 52.0±10.7 years, respectively. The main indications for TPE were hematologic, neurologic, and pulmonary involvement and APS-related symptoms. TPE was preferred in eight patients because of leucopenia and co-infection. SLEDAI was significantly decreased after TPE (16.7±8.3 before vs. 8.8±3.1 after, p=0.001). Both primary APS and SLE-related catastrophic APS (CAPS) patients had completely responded to TPE. The success rate of TPE in patients with thrombocytopenia was lower than patients with hemolytic anemia. The median (IQR 25%-75%) number of TPE sessions was 6.5 (5-10.5). In total, five patients experienced TPE-related major adverse events (catheter infections in three patients, bleeding in one patient, and hypotension in one patient). The median (IQR 25%-75%) follow-up time was 33.5 (6.75-81.25) months. In total, four patients died during follow up, of which three died during the period of TPE administration. Conclusion: Our data suggest that CAPS and other APS-related problems respond well to the TPE treatment. TPE should be kept in mind for the treatment of patients with other features of SLE, especially those resistant to other agents and in the presence of leucopenia.

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Current and emerging treatment options in the management of lupus

Cited by 35 publications

References 136 publications

Determination of thiopurine S -methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry

Determination of thiopurine S -methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry

Mesenchymal Stem Cells Enhance Pulmonary Antimicrobial Immunity and Prevent Following Bacterial Infection

Therapeutic plasma exchange for refractory SLE: A comparison of outcomes between different sub-phenotypes

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