Individualized Pharmacotherapy of Plaque Psoriasis with Oral Methotrexate: Fiction or Reality?

Czech version

Authors: J. Chládek ¹; M. Šimková ²; J. Vaněčková ²; M. Hroch ¹; J. Ettler ²; J. Vávrová ³; K. Ettler ²
Authors‘ workplace: Ústav farmakologie, Lékařská fakulta, Hradec Králové přednosta doc. MUDr. Stanislav Mičuda, Ph. D. ¹; Klinika nemocí kožních a pohlavních, Fakultní nemocnice a Lékařská fakulta, Hradec Králové přednosta doc. MUDr. Karel Ettler, CSc. ²; Ústav klinické biochemie a diagnostiky, Fakultní nemocnice a Lékařská fakulta, Hradec Králové přednosta doc. MUDr. Pavel Živný, CSc. ³
Published in: Čes-slov Derm, 87, 2012, No. 6, p. 221-228
Category: Pharmacologyand Therapy, Clinical Trials

Overview

Methotrexate (MTX) is an effective immunosuppressive drug for moderate-to-severe psoriasis. In an open prospective study patients with chronic plaque psoriasis (n = 25, aged 28–79 yr) were treated with oral methotrexate using an individualized dose guided by plasma concentrations and with folic acid in case the concentration of blood folates dropped below the lower limit of normal range. The aim was to study the relationship between changes in PASI (the Psoriasis Area and Severity Index) and concentrations of MTX polyglutamates (MTXPG) in erythrocytes and blood folates. After 26 weeks, PASI improved from the median of 13.5 (range 2.2–33) by 91% on the average and the frequency of PASI75 (improvement ≥ 75 %) was 76%. There was a correlation between PASI improvement and the ratio of concentrations MTXPG/folates (r_s = 0. 51, P < 0.01). In patients experiencing PASI75, the ratio achieved 0.61 as compared to 0.26 in those with less improvement (P < 0.05). In conclusion, individual-tailored therapy with MTX and folic acid can improve the results in the remission-induction phase of psoriasis treatment. Its efficacy should be compared with other established drug regimens in controlled studies.

Key words:
psoriasis – PASI – methotrexate – folates

Sources

1. AKHYANI, M., CHAMS-DAVATCHI, C., HEMAMI, MR., FATEH, S. Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis. J. Eur. Acad. Dermatol. Venereol., 2010, 24, 12, p. 1447–1451.

2. BARKER, J., HOFFMANN, M., WOZEL, G., ORTONNE, J. P., ZHENG, H., VAN HOOGSTRATEN, H., REICH, K. Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active--controlled, randomized trial (RESTORE1). Br. J. Dermatol., 2011, 165, 5, p. 1109–1117.

3. BOFFA, M. J. Methotrexate for psoriasis: current European practice. A postal survey. J. Eur. Acad. Dermatol. Venereol., 2005, 19, 2, p. 196–202.

4. DUHRA, P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J. Am. Acad. Dermatol, 1993, 28 (3), p. 466–469.

5. FALLAH ARANI, S., NEUMANN, H., HOP, W. C., THIO, H. B. Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial. Br. J. Dermatol., 2011, 164, 4, p. 855–861.

6. FLYTSTRÖM, I., STENBERG, B., SVENSSON, A., BERGBRANT, I. M. Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br. J. Dermatol., 2008, 158, 1, p. 116–121.

7. GRIFFITHS, C. E., BARKER, J. N. Pathogenesis and clinical features of psoriasis. Lancet, 2007, 370, 9583, p. 263–271.

8. GRIM, J., CHLÁDEK, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., KOUDELKOVÁ, V., MARTÍNKOVÁ, J. Modelování farmakokinetiky a farmakodynamiky nízkodávkovaného metotrexátu v léčbě psoriázy pro individualizaci dávkování. Čes-slov Derm, 2002, 77, č. 4, s. 154–162.

9. GRIM, J., CHLÁDEK, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., KOUDELKOVÁ, V., MARTÍNKOVÁ, J., NOŽIČKOVÁ, M. Koncentrace metotrexátu v erytrocytech při nízkodávkovém způsobu podání a jejich vztah k úspěchu léčby psoriázy. Čes-slov Derm, 2001, 76, č. 5, s. 237–242.

10. GRIM, J., CHLÁDEK, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., KOUDELKOVÁ, V., MARTÍNKOVÁ, J. Účinek a farmakokinetika metotrexátu v léčbě psoriázy. Čes-slov derm, 2001, roč. 76, č. 4, s. 183–188.

11. HEYDENDAEL, V. M., SPULS, P. I., OPMEER, B. C. et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N. Engl. J. Med., 2003, 349, 7, p. 658–665.

12. HROCH, M., CHLADEK, J., SIMKOVA, M., VANECKOVA, J., GRIM, J., MARTINKOVA, J. A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment. J. Eur. Acad. Dermatol. Venereol., 2008, 22, 1, p. 19–24.

13. HROCH, M., TUKOVÁ, J., DOLEZALOVÁ, P., CHLÁDEK, J. An improved high-performance liquid chromatography method for quantification of methotrexate polyglutamates in red blood cells of children with juvenile idiopathic arthritis. Biopharm. Drug Dispos., 2009, 30, 3, p. 138–148.

14. CHLÁDEK, J., GRIM, J., MARTÍNKOVÁ, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., KOUDELKOVÁ, V., NOŽIČKOVÁ, M. Pharmacokinetics and pharmacodynamics of low-dose methotrexate in the treatment of psoriasis. Br. J. Clin. Pharmacol., 2002, 54, 2, p. 147–156.

15. CHLÁDEK, J., GRIM, J., MARTÍNKOVÁ, J., ŠIMKOVA, M., VANĚČKOVÁ, J. Low-dose methotrexate pharmacokinetics and pharmacodynamics in the therapy of severe psoriasis. Basic Clin. Pharmacol. Toxicol., 2005, 96, 3, p. 247–248.

16. CHLÁDEK, J., MARTÍNKOVÁ, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., KOUDELKOVÁ, V., NOŽIČKOVÁ, M. Pharmacokinetics of low doses of methotrexate in patients with psoriasis over the early period of treatment. Eur. J. Clin. Pharmacol., 1998, 53, 6, p. 437–444.

17. CHLÁDEK, J., ŠIMKOVÁ, M., VANĚČKOVÁ, J., HROCH, M., CHLÁDKOVA, J., MARTÍNKOVÁ, J., VÁVROVÁ, J., BERÁNEK, M. 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., 2008, 64, 4, p. 347–355.

18. KALB, R. E., STROBER, B., WEINSTEIN, G., LEBWOHL, M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J. Am. Acad. Dermatol., 2009, 60, 5, p. 824–837.

19. KIRBY, B., LYON, C. C., GRIFFITHS, C. E., CHALMERS, R. J. The use of folic acid supplementation in psoriasis patients receiving methotrexate: a survey in the United Kingdom. Clin. Exp. Dermatol., 2000, 25, 4, p. 265–268.

20. MATEŘANKOVÁ, A., SCHMIEDBERGEROVÁ, R., HERCOGOVÁ, J. Kvalita života a psoriáza – první výsledky dotazníkového šetření mezi českými psoriatiky. Čes-slov Dermatol., 2008, roč. 83, č. 6, s. 299–304.

21. MONTAUDIÉ, H., SBIDIAN, E., PAUL, C., MAZA, A., GALLINI, A., ARACTINGI, S., AUBIN, F., BACHELEZ, H., CRIBIER, B., JOLY, P., JULLIEN, D., LE MAÎTRE, M., MISERY, L., RICHARD, M. A., ORTONNE, J. P. Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity. J. Eur. Acad. Dermatol. Venereol., 2011, 25 (Suppl 2), p. 12–18.

22. PATHIRANA, D., ORMEROD, AD., SAIAG, P., SMITH, C. et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J. Eur. Acad. Dermatol. Venereol., 2009, 23 (Suppl 2), p. 1–70.

23. PAUL, C., GALLINI, A., MAZA, A., MONTAUDIÉ, H., SBIDIAN, E., ARACTINGI, S., AUBIN, F., BACHELEZ, H., CRIBIER, B., JOLY, P., JULLIEN, D., LE MAÎTRE, M., MISERY, L., RICHARD, M. A., ORTONNE, J. P. Evidence-based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists. J. Eur. Acad. Dermatol. Venereol., 2011, 25 (Suppl 2), p. 2–11.

24. PREY, S., PAUL, C. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br. J. Dermatol., 2009, 160, 3, p. 622–628.

25. REICH, K., LANGLEY, R. G., PAPP, K. A., ORTONNE, J. P., UNNEBRINK, K., KAUL, M., VALDES, J. M. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N. Engl. J. Med., 2011, 365, 17, p. 1586–1596.

26. SALIM, A., TAN, E., ILCHYSHYN, A., BERTH-JONES, J. Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial. Br. J. Dermatol., 2006, 154, 6, p. 1169–1174.

27. SAURAT, J. H., STINGL, G., DUBERTRET, L., PAPP, K., LANGLEY, R. G., ORTONNE, J. P., UNNEBRINK, K., KAUL, M., CAMEZ, A. CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br. J. Dermatol., 2008, 158, 3, p. 558–566.

28. SHEN, S., O’BRIEN, T., YAP, L. M., PRINCE, H. M., MCCORMACK, C. J. The use of methotrexate in dermatology: a review. Australas J. Dermatol., 2012, 53, 1, p. 1–18.

29. STROBER, B. E., MENON, K. Folate supplementation during methotrexate therapy for patients with psoriasis. J. Am. Acad. Dermatol., 2005, 53, 4, p. 652–659.

30. WARREN, R. B., CHALMERS, R. J., GRIFFITHS, C. E., MENTER, A. Methotrexate for psoriasis in the era of biological therapy. Clin. Exp. Dermatol., 2008, 33, 5, p. 551–554.

31. WHITTLE, S. L., HUGHES, R. A. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford), 2004, 43, 3, p. 267–271.

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Article was published in

Czech-Slovak Dermatology

2012 Issue 6