A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment

Hroch, Miloš; Chládek, Jaroslav; Šimková, M; Vaněčková, J.; Grim, Jiří; Martı́nková, Jiřina

doi:10.1111/j.1468-3083.2007.02264.x

Cited by 26 publications

(35 citation statements)

References 17 publications

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“…Additionally, interpatient variability in dosing of methotrexate is significant, and pharmacokinetic dosing strategies are suggested for initial dosing regimens of low-dose methotrexate in psoriasis. 31 Several pieces of data from this case are unavailable, preventing a "highly probable" association of low-dose methotrexate with the ADR observed in this patient. A methotrexate concentration in a toxic range was not available because it was not obtained until 72 hours after the last dose was given and after one dose of leucovorin had been administered.…”

Section: Discussionmentioning

confidence: 87%

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis

Bookstaver

Norris

Rudisill

et al. 2008

American Journal of Health-System Pharmacy

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Section: Discussionmentioning

confidence: 87%

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis

Bookstaver

Norris

Rudisill

et al. 2008

American Journal of Health-System Pharmacy

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“…Methotrexate increases plasma homocysteine levels in patients with psoriasis 102 , 103 . Metformin (upon long-term treatment) can lower plasma vitamin B 12 104 and increases plasma homocysteine levels 105 , 106 .…”

Section: Resultsmentioning

confidence: 99%

A marriage of two “Methusalem” drugs for the treatment of psoriasis?

Glossmann

Reider

2013

Dermato-Endocrinology

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In this article we present arguments that the “antidiabetic” drug metformin could be useful as an add-on therapy to methotrexate for the treatment of psoriasis and, perhaps, for rheumatoid arthritis as well. Biochemical data suggest that both drugs may share a common cellular target, the AMP-activated protein kinase (AMPK). This enzyme is a master regulator of metabolism and controls a number of downstream targets, e.g., important for cellular growth or function in many tissues including T-lymphocytes. Clinical observations as well as experimental results argue for anti-inflammatory, antineoplastic and antiproliferative activities of metformin and a case-control study suggests that the drug reduces the risk for psoriasis. Patients with psoriasis have higher risk of metabolic syndrome, type 2 diabetes and cardiovascular mortality. Metformin has proven efficacy in the treatment of prediabetes and leads to a pronounced and sustained weight loss in overweight individuals. We expect that addition of metformin to methotrexate can lead to positive effects with respect to the PASI score, reduction of the weekly methotrexate dose and of elevated cardiovascular risk factors in patients with metabolic syndrome and psoriasis. For reasons explained later we suggest that only male, overweight patients are to be included in a pilot trial. On the other side of the coin are concerns that the gastrointestinal side effects of metformin are intolerable for patients under low dose, intermittent methotrexate therapy. Metformin has another side effect, namely interference with vitamin B12 and folate metabolism, leading to elevated homocysteine serum levels. As patients must receive folate supplementation and will be controlled with respect to their B12 status increased hematological toxicity is unlikely to result.

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“…On treating patients with infliximab (2 study arms, n ¼ 21), a period of 1.5 weeks was necessary to achieve a PASI reduction by 25% and a period of 3.7 weeks was necessary to lower the PASI by 50% (Chaudhari et al, 2001;Lemme et al, 2007). Low-dose MTX (5 study arms, n ¼ 329) required time periods of 4.0 and 10.0 weeks for a PASI reduction by 25% and 50%, respectively Hroch et al, 2008;Revicki et al, 2008;Saurat et al, 2008;Reich et al, 2011;Dogra et al, 2012). During treatment with high-dose MTX (3 study arms, n ¼ 92), a 25% reduction in the mean PASI was achieved within a period of 1.9 weeks and a 50% reduction was achieved within a period of 3.9 weeks (Heydendael et al, 2003;Akhyani et al, 2010;Dogra et al, 2012).…”

Section: Characteristics Of the Included Study Armsmentioning

confidence: 99%

“…The Engauge Software allows to match a graph with a given scale and to extract the displayed values. The software was validated performing 25 read outs on six different studies where data were provided in a graphic form as well as in tables or text (Gollnick et al, 2002;Heydendael et al, 2003;Leonardi et al, 2003;Tyring et al, 2007;Hroch et al, 2008;Leonardi et al, 2008;). The mean deviation of the Engauge-extracted data from data provided in texts or tables is considered to be negligible (0.24% ( À 0.16 to 0.64)).…”

Section: Data Extractionmentioning

confidence: 99%

Which Antipsoriatic Drug Has the Fastest Onset of Action?—Systematic Review on the Rapidity of the Onset of Action

Nast¹,

Sporbeck²,

Rosumeck³

et al. 2013

Journal of Investigative Dermatology

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The time necessary for a treatment to become effective is crucial for patients and physicians but has been largely neglected in the reporting and comparison of clinical trials in dermatology. The aim of this systematic review is to determine the time until the onset of action (TOA) of systemic agents approved for moderate-to-severe psoriasis. Primary outcome is the TOA defined as the weighted mean time until 25% of the patients achieved a psoriasis area and severity index (PASI) 75 response. Among the biologics, infliximab has the shortest TOA (3.5 weeks), followed by ustekinumab (high dose 4.6/low dose 5.1 weeks/not weight adapted), adalimumab (4.6 weeks), etanercept (high dose 6.6/low dose 9.5 weeks), and alefacept (high dose 15.4 weeks/low dose: no data). Among the conventional treatments, good data are available for cyclosporine A (CsA; TOA: 6.0 weeks) and limited data are found for methotrexate (MTX; TOA: high dose 3.2/low dose 9.9 weeks). No data are available for fumaric acid esters and retinoids. This systematic review provides clinically relevant information on the onset of action of antipsoriatic agents, although the data currently available allow only a limited assessment. Psoriasis trials should consider including TOA as an additional outcome measure.

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A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment

Cited by 26 publications

References 17 publications

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis

A marriage of two “Methusalem” drugs for the treatment of psoriasis?

Which Antipsoriatic Drug Has the Fastest Onset of Action?—Systematic Review on the Rapidity of the Onset of Action

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