Biomarkers for methotrexate-induced liver injury: Urinary protein profiling of psoriasis patients

Swelm, Rachel P. L. van; Laarakkers, Coby M.; Kooijmans-Otero, Marisol; Jong, E.M.G.J. de; Masereeuw, Rosalinde; Rüssel, Frans G. M.

doi:10.1016/j.toxlet.2013.06.234

Cited by 29 publications

(22 citation statements)

References 36 publications

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“…Liver injury, including progression to fibrosis and cirrhosis, is also linked to MTX exposure [72]. Patients may experience mild, transient, asymptomatic elevation of liver enzymes, which usually resolves with dose reduction or temporary discontinuation of therapy [60].…”

Section: Methotrexatementioning

confidence: 99%

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

McLean

Cross²

2014

Expert Review of Gastroenterology & Hepatology

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Crohn’s disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered.

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Section: Methotrexatementioning

confidence: 99%

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

McLean

Cross²

2014

Expert Review of Gastroenterology & Hepatology

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“…Urinary proteome analysis could identify potentially predictive biomarkers for methotrexate-induced hepatic fibrosis in psoriasis with high cumulative dose of methotrexate 13. Interestingly, our study found psoriasis had more abnormalities in UE in comparison with non-psoriasis controls, and the main manifestation was urine leukocytosis, which suggested that psoriatic patients were prone to urinary infections, particularly as psoriatic patients treated with immunosuppressants or biological agents such as anti-TNF-α agents are at an increased risk of infections.…”

Section: Discussionmentioning

confidence: 61%

Systemic abnormalities of psoriatic patients: a retrospective study

Yin

et al. 2016

CCID

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BackgroundPsoriasis is a chronic immune-mediated inflammatory disease related to the metabolic syndrome, cardiovascular disease, and other comorbidities. However, so far there has been no specific research concerning systemic abnormalities in psoriatic patients.ObjectiveA retrospective study was conducted focusing on the detailed systemic abnormalities in psoriatic patients.MethodsPsoriatic inpatients data was collected from July 2009 to September 2015. The inclusion criteria were first-time hospitalization and without administration of systemic drug therapy or exposure to phototherapy for psoriasis for at least 1 month. Detailed systemic indexes were mainly evaluated.ResultsThe abnormality rates of blood routine examination, urine examination, blood biochemical examination and chest X-ray of 43 psoriatic patients were significantly higher than those of 44 non-psoriasis controls, and psoriasis patients significantly had higher absolute values of leukocytes and neutrophils, and significantly lower values of lymphocytes. Compared with psoriasis vulgaris, erythrodermic psoriasis had significantly higher abnormality rates of blood biochemical examination and serum electrolyte analysis. Erythrodermic psoriasis had significantly higher absolute values of blood leukocytes, neutrophils, and lower serum calcium compared with those of psoriasis vulgaris. The neutrophil-to-lymphocyte ratio of controls was significantly lower than that of psoriatic patients, and neutrophil-to-lymphocyte ratio of erythrodermic psoriasis was significantly higher in comparison with psoriasis vulgaris.ConclusionThis study is the first report in relation to a detailed assessment of systemic abnormalities in psoriatic patients prior to onset of systemic treatment. The systemic condition of psoriatic patients should be observed by clinicians before systemic therapy.

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“…Działanie toksyczne na wątrobę, jak stłuszczenie, martwica, włóknienie okołowrotne i marskość, raportowano u pacjentów z łuszczycą, którym przewlekle podawano MTX [32,33]. Krytyczne stężenie metotreksatu w osoczu, hamujące czynności szpiku kostnego, jest bardzo niskie i wynosi 2×10 -8 mol MTX/l osocza.…”

Section: Główne Skutki Uboczne Leku Metotreksatunclassified

Methotrexate – Genotoxic and teratogenic for medical staff of oncology wards?

Kupczewska-Dobecka¹

2015

Med Pr

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StreszczenieJednym z najczęściej stosowanych leków cytostatycznych jest metotreksat (MTX) należący do antagonistów kwasu foliowego. Jest to substancja w Unii Europejskiej niezaklasyfikowana jako rakotwórcza, a Międzynarodowa Agencja Badań nad Rakiem (International Agency for Research on Cancer -IARC) oceniła, że nie ma dowodów na jej oddziaływanie rakotwórcze u ludzi i zwierząt. Mimo to MTX znalazł się na listach leków niebezpiecznych stosowanych w chemioterapii, głównie ze względu na właściwości genotoksyczne oraz działanie teratogenne, powodowanie toksyczności rozwojowej i szkodliwy wpływ na rozrodczość. Metotreksat wykryto w powietrzu oddziału szpitalnego podczas przygotowywania leku, na poziomie 0,3 µg/m 3 , a także na rękawicach ochronnych oraz czyszczonych powierzchniach pokoi przygotowawczych. Stężenie MTX na polietylenowym pokryciu wyciągu wentylacyjnego wynosiło 645 µg/m 2 . W większości prowadzonych projektów badawczych zidentyfikowano MTX w moczu pracowników opieki medycznej, farmaceutów i personelu pielęgniarskiego, a także pracowników służby zdrowia, którzy byli narażeni w wyniku wtór-nego zanieczyszczenia powierzchni roboczych, odzieży czy pojemników. Najwyższe skumulowane stężenie MTX w 112 próbkach moczu wynosiło 1416 µg u pracowników podłączających i przygotowujących wlewy u pacjentów. Badania przeprowadzone w aptekach wykazały obecność MTX w 60% pobranych prób, a jego maksymalne stężenie wynosiło 15 ng/cm 2 powierzchni tacy do odliczania tabletek. Dotychczas nie zostały ustalone obowiązujące prawnie wartości najwyższych dopuszczalnych stężeń (NDS) metotreksatu w środowisku pracy. Dopuszczalne poziomy narażenia zawodowego niektórzy producenci MTX ustalili w granicach 0,0003-0,0025 mg/m 3 . Naglącą potrzebą jest ustalenie wartości normatywnych. Należy podkreślić, że substancja wchłania się przez skórę, co może istotnie zwiększać narażenie, a pomiar jej stężenia w środowisku pracy może nie wystarczać do oszacowania rzeczywistego narażenia. Med. Pr. 2015;66(2):265-275 Słowa kluczowe: metotreksat, narażenie zawodowe, cytostatyki, najwyższe dopuszczalne stężenie Abstract Methotrexate (MTX) is one of the most widely used cytostatic drugs belonging to the folic acid antagonists. It is a substance non-classified as a carcinogen in the European Union and by the International Agency for Research on Cancer (IARC) as there is no evidence of its carcinogenicity to humans and animals. Nevertheless, MTX has been placed on the list of dangerous drugs used in chemotherapy, mainly due to genotoxic and teratogenic effects, causing developmental toxicity and reproductive toxicity. Methotrexate was determined in the hospital ward air during the preparation of a medicament at a level of 0.3 mg/m 3 , as well as on protective gloves and preparatory room surfaces. In most research projects MTX was identified in the urine of health care workers, pharmacists and nursing staff. The highest cumulative concentration of MTX in 112 urine samples was 1416 mg in workers preparing infusions for patients. Studies carried out in ph...

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Biomarkers for methotrexate-induced liver injury: Urinary protein profiling of psoriasis patients

Cited by 29 publications

References 36 publications

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

Systemic abnormalities of psoriatic patients: a retrospective study

Methotrexate – Genotoxic and teratogenic for medical staff of oncology wards?

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