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The effect of folic acid supplementation on the pharmacokinetics and pharmacodynamics of oral methotrexate during the remission-induction period of treatment for moderate-to-severe plaque psoriasis

  • Clinical Trial
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Abstract

Objective

We assessed the effect of folic acid (FA) on the pharmacokinetics and pharmacodynamics of low-dose oral methotrexate (MTX) during the remission-induction phase of psoriasis treatment.

Methods

In a 32-week, open-label, two-way cross-over study, patients (n = 20, seven men, aged 35–70 years) with moderate-to-severe plaque psoriasis were randomly assigned to receive MTX plus FA (20 mg/week) for 16 weeks followed by MTX monotherapy (three doses of MTX separated by 12-h intervals once a week) for an additional 16 weeks (treatment arm A, n = 10) or to receive the opposite sequence of treatments (arm B, n = 10). Dosing of MTX was individualised with the help of pre-study evaluation of plasma MTX pharmacokinetics. The Psoriasis Area and Severity Index (PASI), biochemistry and haematology tests and erythrocyte concentration of MTX polyglutamates (MTXPG) were evaluated throughout the study.

Results

In arms A and B, the mean (range) concentrations of MTXPG (nmol/L) were comparable [week 16: 96.2 (32.0–157) vs. 111 (73.7–175), P = 0.32; week 32: 103 (55.8–173) vs. 83.6 (27.4–129), P = 0.24]. After 16 weeks, the mean±SEM PASI decreased from 20.1 ± 2.1 to 8.8 ± 1.3 in arm A, while a greater reduction from 27.2 ± 2.1 to 5.1 ± 1.0 occurred in arm B (P < 0.001). Positive correlations were found between the percent improvement in PASI at week 16 and the ratios of the concentration of MTXPG to plasma folate (rho = 0.59, P = 0.008) or RBC folate concentration (rho = 0.56, P = 0.013). Due to an accelerated decline in PASI in arm A and a trend to its worsening in arm B after crossing over of treatments, the mean absolute PASI scores in both arms were comparable at week 32.

Conclusion

The antipsoriatic effect of MTX during the remission-induction phase of treatment is influenced by folate status and may be significantly less if combined treatment with FA is used, irrespective of pre-treatment folate levels. The individual tailoring of MTX dosing needs further attention because the mean percent PASI improvement from baseline was 83% and the inter-patient variability in response was low after 16 weeks of monotherapy with MTX.

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Acknowledgements

The study was supported by grants from the Czech Ministry of Health no. NR7947-3/2004 and Czech Ministry of Education and Youth MSM 0021620820 and 1P05OC066.

Statement of competing interests

All authors (Jaroslav Chladek, Marie Simkova, Jaroslava Vaneckova, Milos Hroch, Jirina Chladkova, Jirina Martínková, Jaroslava Vávrová, Martin Beránek) declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pharmacology and Department of Biochemistry, Faculty of Medicine, Charles University, Simkova 870, 500 38, Hradec Kralove, Czech Republic

    Jaroslav Chládek

  2. Department of Dermatology, University Hospital, Hradec Kralove, Czech Republic

    Marie Simková & Jaroslava Vanecková

  3. Department of Pharmacology, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic

    Milos Hroch

  4. Department of Paediatrics, University Hospital, Hradec Kralove, Czech Republic

    Jirina Chládkova

  5. Department of Pharmacology, Faculty of Medicine, Charles University, Simkova 870, 500 38, Hradec Kralove, Czech Republic

    Jirina Martínková

  6. Department of Clinical Biochemistry and Diagnostics, University Hospital, Hradec Kralove, Czech Republic

    Jaroslava Vávrová & Martin Beránek

Authors
  1. Jaroslav Chládek
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  2. Marie Simková
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Correspondence to Jaroslav Chládek.

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Chládek, J., Simková, M., Vanecková, J. et al. The effect of folic acid supplementation on the pharmacokinetics and pharmacodynamics of oral methotrexate during the remission-induction period of treatment for moderate-to-severe plaque psoriasis. Eur J Clin Pharmacol 64, 347–355 (2008). https://doi.org/10.1007/s00228-007-0442-x

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  • DOI: https://doi.org/10.1007/s00228-007-0442-x

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