High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients—A Preliminary Study

Sandhu, Amit; Dhir, Varun; Bhatnagar, Archana; Dhawan, Veena; Kaur, Jasbinder; Sood, Ankita; Naidu, Gsrsnk; Ahmad, Shabeer; Varma, Neelam; Sharma, Aman; Sharma, Shefali

doi:10.1097/ftd.0000000000000375

Cited by 16 publications

(15 citation statements)

References 23 publications

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“…Была установлена статистически значимая корреляция максимального уровня МТПГ 2 со снижением активности заболевания по индексу DAS28 [18], а также увеличения уровня МТПГ в эритроцитах со снижением индекса DAS28 [19]. Имеются указания, что более высокая концентрация МТПГ является предиктором развития нежелательных реакций у больных РА, но отсутствует связь между уровнем МТПГ и эффективностью препарата [20,21]. Разнородность вышеизложенных сведений можно частично объяснить разнообразием методик определения уровня метаболитов МТ.…”

Section: Discussionunclassified

The relationship between the efficacy of methotrexate in rheumatoid arthritis and the achieved level of its polyglutamates in erythrocytes (pilot study)

Гриднева¹,

Муравьев²,

Демидова³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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Therapeutic control of the methotrexate (MT) polyglutamates (MTPG) level in erythrocytes can be an objective marker of the effective dose of MT prescribed for rheumatoid arthritis (RA).Objective: to assess the relationship between the level of MTPG in red blood cells and efficacy of the MT dose used by RA patients.Subjects and methods. The study included 60 patients with RA (44 women and 16 men over 18 years) who met the criteria of the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) 2010 and received MT ≥20 mg/week subcutaneously for ≥12 weeks. The patients were divided into two groups of comparable age, sex, alcohol intake, number of smokers, body mass index (BMI), depending on the presence (group 1; n=30) or absence (group 2; n=30) of the effect of MT, according to the EULAR efficacy criteria (DAS28). The concentration of MTPG (total MTPG and metabolites of MTPG 1, 2, 3, 4, 5) was determined in erythrocytes by high-performance liquid chromatography with mass spectrometric detection.Results and discussion. It was found that the levels of total MTPG and MTPG1, 2, 3, 5 in erythrocytes did not differ in groups of responders and nonresponders, and the dose of MT was comparable in both groups. At the same time, the level of MTPG4 in the first group was significantly higher (26.4±6.1 nmol/l; p=0.023) than in the second one (22.1±6.8 nmol/l). Analysis of the ROC curve showed that the values of MTPG4 <22.5 nmol/l corresponded to the absence of effect of MT. The area under the curve was 0.672 (95% confidence interval 0.536–0.808 (p=0.022), sensitivity 77%, specificity 53.3%.Conclusion. For effective treatment of patients with RA MT dose should provide MTPG4 level in red blood cells ≥22.5 nmol/l.

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Section: Discussionunclassified

The relationship between the efficacy of methotrexate in rheumatoid arthritis and the achieved level of its polyglutamates in erythrocytes (pilot study)

Гриднева¹,

Муравьев²,

Демидова³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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“…Recently, Chen et al 19 reported the usage of an LC tandem mass spectrometry assay (LC/MS/MS) for the measurement of MTX-Glu1-5 in Caco-2 cells, showing improved selectivity and lower detection limits. In addition, according to various studies, 20 MTX-Glu was analyzed using HPLC.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Chen et al 19 reported the usage of an LC tandem mass spectrometry assay (LC/MS/MS) for the measurement of MTX‐Glu1–5 in Caco‐2 cells, showing improved selectivity and lower detection limits. In addition, according to various studies, 20 MTX‐Glu was analyzed using HPLC. Previously, Garcia‐Ac et al 21 used chromatography ionization techniques such as APPI, APCI, and ESI for the LC‐MS/MS analysis of bezafibrate, cyclophosphamide, and MTX.…”

Section: Introductionmentioning

confidence: 99%

Analysis of hair and plasma samples for methotrexate (MTX) and metabolite using high‐performance liquid chromatography triple quadrupole mass spectrometry (LC‐MS/MS) detection

Kim

Yoo²,

Yoo

et al. 2020

J Mass Spectrom

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Methotrexate (MTX), a folate antagonist, is the anchor drug used to treat several diseases. Therapeutic effects are attributed to intracellular levels of various methotrexate conjugates that are present in the cell as polyglutamates (MTX-Glu). The present study was conducted to develop a new liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)-based assay to separately quantitate the MTX-Glu in hair cells, red blood cells, and serum using internal standards. Sample preparation consisted of extraction with an organic solution followed by solid-phase extraction. The presented methodology was applied for the analysis of methotrexate and its polyglutamates in hair cells, red blood cells, and serum obtained from clinical patients. The developed LC-ESI-MS/MS method for the quantitative measurement of MTX-Glu was both sensitive and precise within the clinically relevant range. This method is possibly be superior with respect to sensitivity, selectivity, and speed than all previously described approaches and can be easily applied in routine clinical tests owing to the combination of a simple pretreatment process with robust LC-MS/MS.

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“…A. Sandhu и соавт. [27] установили, что более высокая концентрация МТПГ3 является предиктором развития НР у больных РА, но они не установили связи между концентрацией МТПГ и ответом на терапию.…”

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What do we know about the possibility of predicting the potential efficacy and safety of methotrexate, by measuring the concentration of its metabolites in rheumatoid arthritis?

Гриднева¹,

Аронова²,

Sygyrta³

et al. 2020

Sovremennaâ revmatologiâ

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Rheumatoid arthritis (RA) is characterized by a progressive course with the formation of joint deformities and the development of severe functional disorders. The most favorable conditions for changing the course of the disease emerge in the first months after its onset. Methotrexate (MTX) occupies a leading position in the treatment of RA. There is a need to develop tools that will be able to predict the efficacy and tolerability of MTX at the earliest stages of RA treatment. The concentration of active metabolites of MTX is considered as a potential biomarker that enables one to predict what response to therapy with this drug will be.The paper analyzes the most relevant works devoted to the study of the concentration of active MTX metabolites polyglutamates (MTX PGs) in patients with RA. It is shown that the presented studies do not cover all the possibilities of therapeutic drug monitoring, in particular the determination of the levels of MTX PGs in mononuclear cells over time. Further investigation is needed to develop an objective approach to prescribing MTX in RA patients.

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High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients—A Preliminary Study

Abstract: In this preliminary study, higher levels of RBC MTX-glu3 were found to be the independent predictors for adverse effects in rheumatoid arthritis patients.

Cited by 16 publications

References 23 publications

The relationship between the efficacy of methotrexate in rheumatoid arthritis and the achieved level of its polyglutamates in erythrocytes (pilot study)

The relationship between the efficacy of methotrexate in rheumatoid arthritis and the achieved level of its polyglutamates in erythrocytes (pilot study)

Analysis of hair and plasma samples for methotrexate (MTX) and metabolite using high‐performance liquid chromatography triple quadrupole mass spectrometry (LC‐MS/MS) detection

What do we know about the possibility of predicting the potential efficacy and safety of methotrexate, by measuring the concentration of its metabolites in rheumatoid arthritis?

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