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Effectiveness of methotrexate in moderate to severe psoriasis patients: real-world registry data from the Swiss Dermatology Network for Targeted Therapies (SDNTT)

  • Mathias Drach
  • Karolina Papageorgiou
  • Julia-Tatjana Maul
  • Vahid Djamei
  • Nikhil Yawalkar
  • Peter Häusermann
  • Florian Anzengruber
  • Alexander A. NavariniEmail author
Original Paper

Abstract

Methotrexate (MTX) is a frequently used anti-psoriatic drug that is commonly recommended in international psoriasis guidelines. It is effective in treating skin lesions, nail changes and psoriatic arthritis. In 2017 a prospective, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, commonly known as the METOP trial, was published assessing the effectiveness and safety of subcutaneous administration of methotrexate. Because trial data do not always relate to real-life data with unselected patient populations, we wanted to determine whether the data obtained in the METOP-trial correspond to real-life registry data from our Swiss Dermatology Network for Targeted Therapies (SDNTT). Data of 449 patients with moderate to severe psoriasis who participated in the SDNTT registry between 2011 and 1st of July 2017 were analyzed. Only patients receiving methotrexate s.c. were included. 66 patients under MTX were included into this study. Baseline PASI was 6.3 ± 3.8 (SDNTT) compared to 15.9 ± 5.9 in the METOP trial. In our cohort, only 18% of all patients reached PASI 75 after 12 weeks, 6% showed a complete remission (PASI 100) compared to 41% and 4% in the METOP trial after 16 weeks. 22.7% of all patients showed increased liver enzymes in either study and nausea was seen in 15% (SDNTT) versus 22% (METOP) of patients. No severe adverse events were observed in our cohort. Compared to the METOP-trial, the response rates seen our real-world cohort were distinctly lower.

Keywords

Methotrexate Psoriasis Folate acid METOP SDNTT MTX 

Notes

Compliance with ethical standards

Conflict of interest

Mathias Drach has no conflict of interest. Karolina Papageorgiou has no conflict of interest. Julia-Tatjana Maul is an employee of USZ and holds a “Filling the GAP” scholarship. Vahid Djamei has no conflict of interest. Nikhil Yawalkar has received honoraria for consulting and advisory board attendance from Abbvie, Almirall, Amgen, Celgene, Eli Lilly, Galderma, Gebro, Janssen, Leo, Novartis, MSD and Pfizer. Peter Häusermann has received honoraria for consulting and advisory board attendance from Abbvie, Almirall, Celgene, Eli Lilly, Galderma, Janssen, Leo and Novartis. Florian Anzengruber is an employee of the University Hospital Zurich. He has received honoraria from Abbvie, Celgene, Leo Pharma, Galderma, Eli Lilly, Almirall, Janssen—Cilag and Novartis, but has no financial interest, nor holds any shares of any pharmaceutical company. Alexander A. Navarini is on the advisory board of AbbVie, Pfizer, Novartis, Celgene, MSD, Galderma, Sanofi, Boehringer-Ingelheim, Lilly.

References

  1. 1.
    Ahlehoff O, Skov L, Gislason G, Gniadecki R, Iversen L, Bryld LE et al (2015) Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort. J Eur Acad Dermatol Venereol 29(6):1128–1134Google Scholar
  2. 2.
    Ahlehoff O, Skov L, Gislason G, Lindhardsen J, Kristensen SL, Iversen L et al (2013) Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study. J Intern Med 273(2):197–204Google Scholar
  3. 3.
    Andersson SE, Johansson LH, Lexmuller K, Ekstrom GM (2000) Anti-arthritic effect of methotrexate: is it really mediated by adenosine? Eur J Pharm Sci 9(4):333–343Google Scholar
  4. 4.
    Anzengruber F, Drach M, Maul JT, Kolios AG, Meier B, Navarini AA (2018) Therapy response was not altered by HLA-Cw6 status in psoriasis patients treated with secukinumab: a retrospective case series. J Eur Acad Dermatol Venereol 32(7):e274–e276Google Scholar
  5. 5.
    Anzengruber F, Ghosh A, Maul JT, Drach M, Navarini AA (2017) Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis. Psoriasis (Auckl) 8:7–11Google Scholar
  6. 6.
    Barker J, Hoffmann M, Wozel G, Ortonne JP, Zheng H, van Hoogstraten H et al (2011) 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 165(5):1109–1117Google Scholar
  7. 7.
    Bendtzen K (2011) Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 63(4):867–870Google Scholar
  8. 8.
    Braun J, Kastner P, Flaxenberg P, Wahrisch J, Hanke P, Demary W et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 58(1):73–81Google Scholar
  9. 9.
    Budzik GP, Colletti LM, Faltynek CR (2000) Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line. Life Sci 66(23):2297–2307Google Scholar
  10. 10.
    Carrascosa JM, Vilavella M, Garcia-Doval I, Carretero G, Vanaclocha F, Dauden E et al (2014) Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry. J Eur Acad Dermatol Venereol 28(7):907–914Google Scholar
  11. 11.
    Churton S, Brown L, Shin TM, Korman NJ (2014) Does treatment of psoriasis reduce the risk of cardiovascular disease? Drugs 74(2):169–182Google Scholar
  12. 12.
    Coates LC, Helliwell PS (2016) Methotrexate efficacy in the tight control in psoriatic arthritis study. J Rheumatol 43(2):356–361Google Scholar
  13. 13.
    Cronstein BN, Naime D, Ostad E (1993) The antiinflammatory mechanism of methotrexate Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 92(6):2675–2682Google Scholar
  14. 14.
    Crowley JJ, Weinberg JM, Wu JJ, Robertson AD, Van Voorhees AS, National Psoriasis F (2015) Treatment of nail psoriasis: best practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol 151(1):87–94Google Scholar
  15. 15.
    Demirsoy EO, Kiran R, Salman S, Caglayan C, Akturk AS, Bayramgurler D et al (2013) Effectiveness of systemic treatment agents on psoriatic nails: a comparative study. J Drugs Dermatol 12(9):1039–1043Google Scholar
  16. 16.
    Garman RD, Munroe K, Richards SM (2004) Methotrexate reduces antibody responses to recombinant human alpha-galactosidase A therapy in a mouse model of Fabry disease. Clin Exp Immunol 137(3):496–502Google Scholar
  17. 17.
    Gerards AH, de Lathouder S, de Groot ER, Dijkmans BA, Aarden LA (2003) Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology (Oxford) 42(10):1189–1196Google Scholar
  18. 18.
    Gisondi P, Altomare G, Ayala F, Bardazzi F, Bianchi L, Chiricozzi A et al (2017) Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol 31(5):774–790Google Scholar
  19. 19.
    Grover C, Daulatabad D, Singal A (2017) Role of nail bed methotrexate injections in isolated nail psoriasis: conventional drug via an unconventional route. Clin Exp Dermatol 42(4):420–423Google Scholar
  20. 20.
    Gulliver WP, Young HM, Bachelez H, Randell S, Gulliver S, Al-Mutairi N (2016) Psoriasis patients treated with biologics and methotrexate have a reduced rate of myocardial infarction: a collaborative analysis using international cohorts. J Cutan Med Surg 20(6):550–554Google Scholar
  21. 21.
    Gumusel M, Ozdemir M, Mevlitoglu I, Bodur S (2011) Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. J Eur Acad Dermatol Venereol 25(9):1080–1084Google Scholar
  22. 22.
    Helliwell PS, Taylor WJ, Group CS (2008) Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs—comparison of drugs and adverse reactions. J Rheumatol 35(3):472–476Google Scholar
  23. 23.
    Hu SC, Lan CE (2017) Psoriasis and cardiovascular comorbidities: focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci 18(10):2211Google Scholar
  24. 24.
    Hugh J, Van Voorhees AS, Nijhawan RI, Bagel J, Lebwohl M, Blauvelt A et al (2014) From the Medical Board of the National Psoriasis Foundation: the risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. J Am Acad Dermatol 70(1):168–177Google Scholar
  25. 25.
    Joseph A, Munroe K, Housman M, Garman R, Richards S (2008) Immune tolerance induction to enzyme-replacement therapy by co-administration of short-term, low-dose methotrexate in a murine Pompe disease model. Clin Exp Immunol 152(1):138–146Google Scholar
  26. 26.
    Kingsley GH, Kowalczyk A, Taylor H, Ibrahim F, Packham JC, McHugh NJ et al (2012) A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford) 51(8):1368–1377Google Scholar
  27. 27.
    Kolios AG, Yawalkar N, Anliker M, Boehncke WH, Borradori L, Conrad C et al (2016) Swiss S1 guidelines on the systemic treatment of psoriasis vulgaris. Dermatology 232(4):385–406Google Scholar
  28. 28.
    Malgarini RB, Pimpinella G (2012) Briakinumab versus methotrexate for psoriasis. N Engl J Med 366(4):379 (author reply 80) Google Scholar
  29. 29.
    Mason KJ, Williams S, Yiu ZZN, McElhone K, Ashcroft DM, Kleyn CE et al (2019) Persistence and effectiveness of nonbiologic systemic therapies for moderate-to-severe psoriasis in adults: a systematic review. Br J Dermatol.  https://doi.org/10.1111/bjd.17625 Google Scholar
  30. 30.
    Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB et al (2008) Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 58(5):826–850Google Scholar
  31. 31.
    Mokni S, Ameur K, Ghariani N, Sriha B, Belajouza C, Denguezli M et al (2018) A case of nail psoriasis successfully treated with intralesional methotrexate. Dermatol Ther (Heidelb). 8(4):647–651Google Scholar
  32. 32.
    Morgado-Carrasco D, Fusta-Novell X, Riera Monroig J, Mascaro Galy JM (2017) The METOP Study: further evidence for the use of subcutaneous methotrexate in psoriasis. Actas Dermosifiliogr 108(9):865–866Google Scholar
  33. 33.
    Nast A, Gisondi P, Ormerod AD, Saiag P, Smith C, Spuls PI et al (2015) European S3-guidelines on the systemic treatment of psoriasis vulgaris–update 2015–short version–EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol 29(12):2277–2294Google Scholar
  34. 34.
    Nesher G, Moore TL (1990) The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine. Arthritis Rheum 33(7):954–959Google Scholar
  35. 35.
    Nishida C, Ko GT, Kumanyika S (2010) Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr 64(1):2–5Google Scholar
  36. 36.
    Parisi R, Symmons DP, Griffiths CE, Ashcroft DM, Identification, Management of P et al (2013) Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 133(2):377–385Google Scholar
  37. 37.
    Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS (2005) Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 52(2):262–267Google Scholar
  38. 38.
    Raychaudhuri SP, Raychaudhuri SK (2009) Biologics: target-specific treatment of systemic and cutaneous autoimmune diseases. Indian J Dermatol 54(2):100–109Google Scholar
  39. 39.
    Reich K, Langley RG, Papp KA, Ortonne JP, Unnebrink K, Kaul M et al (2011) A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med 365(17):1586–1596Google Scholar
  40. 40.
    Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156(9):3435–3442Google Scholar
  41. 41.
    Sanchez-Regana M, Sola-Ortigosa J, Alsina-Gibert M, Vidal-Fernandez M, Umbert-Millet P (2011) Nail psoriasis: a retrospective study on the effectiveness of systemic treatments (classical and biological therapy). J Eur Acad Dermatol Venereol 25(5):579–586Google Scholar
  42. 42.
    Saricaoglu H, Oz A, Turan H (2011) Nail psoriasis successfully treated with intralesional methotrexate: case report. Dermatology 222(1):5–7Google Scholar
  43. 43.
    Saurat JH, Langley RG, Reich K, Unnebrink K, Sasso EH, Kampman W (2011) Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study. Br J Dermatol 165(2):399–406Google Scholar
  44. 44.
    Shiroky JB, Neville C, Esdaile JM, Choquette D, Zummer M, Hazeltine M et al (1993) Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis Results of a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 36(6):795–803Google Scholar
  45. 45.
    Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM et al (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64(5):625–639Google Scholar
  46. 46.
    Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73(3):492–509Google Scholar
  47. 47.
    Smolenska Z, Kaznowska Z, Zarowny D, Simmonds HA, Smolenski RT (1999) Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis. Rheumatology (Oxford) 38(10):997–1002Google Scholar
  48. 48.
    Su YS, Yu HS, Li WC, Ko YC, Chen GS, Wu CS et al (2013) Psoriasis as initiator or amplifier of the systemic inflammatory March: impact on development of severe vascular events and implications for treatment strategy. J Eur Acad Dermatol Venereol 27(7):876–883Google Scholar
  49. 49.
    Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673Google Scholar
  50. 50.
    van Ede AE, Laan RF, Blom HJ, De Abreu RA, van de Putte LB (1998) Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 27(5):277–292Google Scholar
  51. 51.
    Warren RB, Mrowietz U, von Kiedrowski R, Niesmann J, Wilsmann-Theis D, Ghoreschi K et al (2017) An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389(10068):528–537Google Scholar
  52. 52.
    Weinblatt ME, Kaplan H, Germain BF, Block S, Solomon SD, Merriman RC et al (1994) Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. Arthritis Rheum 37(10):1492–1498Google Scholar
  53. 53.
    Wu JJ, Rowan CG, Bebchuk JD, Anthony MS (2015) No association between TNF inhibitor and methotrexate therapy versus methotrexate in changes in hemoglobin A1C and fasting glucose among psoriasis, psoriatic arthritis, and rheumatoid arthritis patients. J Drugs Dermatol 14(2):159–166Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mathias Drach
    • 1
    • 2
  • Karolina Papageorgiou
    • 1
    • 2
  • Julia-Tatjana Maul
    • 1
    • 2
  • Vahid Djamei
    • 1
    • 2
  • Nikhil Yawalkar
    • 3
  • Peter Häusermann
    • 4
  • Florian Anzengruber
    • 1
    • 2
  • Alexander A. Navarini
    • 4
    Email author
  1. 1.Department of DermatologyUniversity Hospital ZurichZurichSwitzerland
  2. 2.Department of ImmunologyUniversity Hospital ZurichZurichSwitzerland
  3. 3.Department of Dermatology, Inselspital, Bern University HospitalUniversity of BernBernSwitzerland
  4. 4.Department of DermatologyUniversity Hospital BaselBaselSwitzerland

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