Drug survival of methotrexate and predictor factors for discontinuation in psoriasis.
Journal
International journal of dermatology
ISSN: 1365-4632
Titre abrégé: Int J Dermatol
Pays: England
ID NLM: 0243704
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
revised:
23
02
2023
received:
24
11
2022
accepted:
02
03
2023
medline:
19
4
2023
pubmed:
25
3
2023
entrez:
24
3
2023
Statut:
ppublish
Résumé
Methotrexate (MTX) is a systemic therapy largely used for moderate-severe psoriasis. There is a lack of data on its use in daily practice and particularly on its long-term effectiveness and survival in psoriasis. We performed a single-centered, retrospective, observational study to evaluate the drug survival of MTX in patients with psoriasis, treated in monotherapy with MTX between March 2015 and March 2022. Clinical and demographic characteristics were extracted from files of the patients. The drug survival was analyzed using Kaplan-Meier survival curves, considering separately overall discontinuation, discontinuation due to MTX ineffectiveness, and discontinuation due to adverse events. Multivariable Cox regression analyses were carried out including clinically meaningful variables. A total of 199 patients were included; 148 (74.4%) suspended MTX during the observation period. The reasons for discontinuation were adverse events (39.2%), ineffectiveness (38.5%), remission of psoriasis (12.2%), and other reasons (10.1%). Average duration of therapy was 10.1 months. Patients who remained on therapy after 1, 2, and 5 years of treatment were respectively 46.9, 35.6, and 29.3%. Positive predictive factors for therapy continuation were increasing age and the use of >15 mg of MTX for a period >3 months; the only negative predictive factor was the clinical variant of palmoplantar pustular. MTX is a valuable, cost-effective option for long-term treatment of psoriasis although drug survival is not comparable with that of biological treatments. Studies are needed to better understand the best dosing regimen to use, with the aim of achieving the best clinical outcomes and the lowest rate of side effects with this drug.
Sections du résumé
BACKGROUND
BACKGROUND
Methotrexate (MTX) is a systemic therapy largely used for moderate-severe psoriasis. There is a lack of data on its use in daily practice and particularly on its long-term effectiveness and survival in psoriasis.
METHODS
METHODS
We performed a single-centered, retrospective, observational study to evaluate the drug survival of MTX in patients with psoriasis, treated in monotherapy with MTX between March 2015 and March 2022. Clinical and demographic characteristics were extracted from files of the patients. The drug survival was analyzed using Kaplan-Meier survival curves, considering separately overall discontinuation, discontinuation due to MTX ineffectiveness, and discontinuation due to adverse events. Multivariable Cox regression analyses were carried out including clinically meaningful variables.
RESULTS
RESULTS
A total of 199 patients were included; 148 (74.4%) suspended MTX during the observation period. The reasons for discontinuation were adverse events (39.2%), ineffectiveness (38.5%), remission of psoriasis (12.2%), and other reasons (10.1%). Average duration of therapy was 10.1 months. Patients who remained on therapy after 1, 2, and 5 years of treatment were respectively 46.9, 35.6, and 29.3%. Positive predictive factors for therapy continuation were increasing age and the use of >15 mg of MTX for a period >3 months; the only negative predictive factor was the clinical variant of palmoplantar pustular.
CONCLUSIONS
CONCLUSIONS
MTX is a valuable, cost-effective option for long-term treatment of psoriasis although drug survival is not comparable with that of biological treatments. Studies are needed to better understand the best dosing regimen to use, with the aim of achieving the best clinical outcomes and the lowest rate of side effects with this drug.
Substances chimiques
Methotrexate
YL5FZ2Y5U1
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-656Informations de copyright
© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.
Références
Ryan TJ, Vickers HR, Salem SN, Callender ST, Badenoch J. The treatment of psoriasis with folic acid antagonists. Br J Dermatol. 1964;76:555-64.
Hayashi H, Tazoe Y, Tsuboi S, Horino M, Morishita M, Arai T, et al. A single nucleotide polymorphism of reduced folate carrier 1 predicts methotrexate efficacy in Japanese patients with rheumatoid arthritis. Drug Metab Pharmacokinet. 2013;28(2):164-8.
Puig L. Methotrexate: new therapeutic approaches. Actas Dermosifiliogr. 2014;105(6):583-9.
Olsen EA. The pharmacology of methotrexate. J Am Acad Dermatol. 1991;25(2 Pt 1):306-18.
Yan K, Xu W, Huang Y, Zhang Z, Huang Q, Xin KZ, et al. Methotrexate restores the function of peripheral blood regulatory T cells in psoriasis vulgaris via the CD73/AMPK/mTOR pathway. Br J Dermatol. 2018;179(4):896-905.
Thomas S, Fisher KH, Snowden JA, Danson SJ, Brown S, Zeidler MP. Methotrexate is a JAK/STAT pathway inhibitor. PLoS One. 2015;10(7):e0130078. Published 2015 Jul 1.
Montaudié H, Sbidian E, Paul C, Maza A, Gallini A, Aractingi S, et al. 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):12-8.
Dogra S, Mahajan R. Systemic methotrexate therapy for psoriasis: past, present and future. Clin Exp Dermatol. 2013;38(6):573-88.
Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. 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):558-66.
Carretero G, Puig L, Dehesa L, Carrascosa JM, Ribera M, Sánchez-Regaña M, et al. Metotrexato: guía de uso en psoriasis [Guidelines on the use of methotrexate in psoriasis]. Actas Dermosifiliogr. 2010;101(7):600-13. Spanish.
Al-Awadhi A, Dale P, McKendry RJ. Pancytopenia associated with low dose methotrexate therapy. A regional survey. J Rheumatol. 1993;20(7):1121-5.
Chen TJ, Chung WH, Chen CB, Hui RC, Huang YH, Lu YT, et al. Methotrexate-induced epidermal necrosis: a case series of 24 patients. J Am Acad Dermatol. 2017;77(2):247-255.e2.
Mohyuddin T, Elyan M, Kushner I. Pericarditis: a rare complication of methotrexate therapy. Clin Rheumatol. 2007;26(12):2157-8.
Burkhart CG. Treatment of psoriasis with methotrexate and folinic acid. J Am Acad Dermatol. 1980;3(2):207-8.
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):622-8.
Kozma C, Ramasethu J. Methotrexate and misoprostol teratogenicity: further expansion of the clinical manifestations. Am J Med Genet A. 2011;155A(7):1723-8.
Chi CC, Wang SH. Efficacy and cost-efficacy of biologic therapies for moderate to severe psoriasis: a meta-analysis and cost-efficacy analysis using the intention-to-treat principle. Biomed Res Int. 2014;2014:862851.
Puig L, Carrascosa JM, Daudén E, Sulleiro S, Guisado C. Drug survival of conventional systemic and biologic therapies for moderate-to-severe psoriasis in clinical practice in Spain: prospective results from the SAHARA study. J Dermatolog Treat. 2020;31(4):344-51.
Egeberg A, Ottosen MB, Gniadecki R, Broesby-Olsen S, Dam TN, Bryld LE, et al. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol. 2018;178(2):509-19.
Coates LC, Merola JF, Grieb SM, Mease PJ, Callis DK. Methotrexate in psoriasis and psoriatic arthritis. J Rheumatol Suppl. 2020;96:31-5.
Carrascosa JM, de la Cueva P, Ara M, Puig L, Bordas X, Carretero G, et al. Methotrexate in moderate to severe psoriasis: review of the literature and expert recommendations. Actas Dermosifiliogr. 2016;107(3):194-206.
Otero ME, van den Reek JM, Seyger MM, van de Kerkhof PC, Kievit W, de Jong EM. Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE. Br J Dermatol. 2017;177(2):497-504.
Cabello Zurita C, Grau Pérez M, Hernández Fernández CP, González Quesada A, Valerón Almazán P, Vilar Alejo J, et al. Effectiveness and safety of methotrexate in psoriasis: an eight-year experience with 218 patients. J Dermatolog Treat. 2017;28(5):401-5.
Maul JT, Djamei V, Kolios AGA, Meier B, Czernielewski J, Jungo P, et al. Efficacy and survival of systemic psoriasis treatments: an analysis of the swiss registry SDNTT. Dermatology. 2016;232(6):640-7.
Van Dooren-Greebe RJ, Kuijpers AL, Mulder J, De Boo T, Van de Kerkhof PC. Methotrexate revisited: effects of long-term treatment in psoriasis. Br J Dermatol. 1994;130(2):204-10.
Shalom G, Zisman D, Harman-Boehm I, Biterman H, Greenberg-Dotan S, Polishchuk I, et al. Factors associated with drug survival of methotrexate and acitretin in patients with psoriasis. Acta Derm Venereol. 2015;95(8):973-7.
Ozkok Akbulut T, Topaloglu Demir F, Oguz Topal I, Kara Polat A, Karadag AS, Aslan Kayiran M, et al. Drug survival and predictor factors for discontinuation of methotrexate in psoriasis: a real-life multicenter study. Int J Dermatol. 2021;60(9):1140-7.
Sandhu K, Kaur I, Kumar B, Saraswat A. Efficacy and safety of cyclosporine versus methotrexate in severe psoriasis: a study from north India. J Dermatol. 2003;30(6):458-63.
El-Eishi NH, Kadry D, Hegazy RA, Rashed L. Estimation of tissue osteopontin levels before and after different traditional therapeutic modalities in psoriatic patients. J Eur Acad Dermatol Venereol. 2013;27(3):351-5.
Singh SK, Singnarpi SR. Safety and efficacy of methotrexate (0.3 mg/kg/week) versus a combination of methotrexate (0.15 mg/kg/week) with cyclosporine (2.5 mg/kg/day) in chronic plaque psoriasis: a randomised non-blinded controlled trial. Indian J Dermatol Venereol Leprol. 2021;87(2):214-22.
Attwa EM, Elkot RA, Abdelshafey AS, Hafez AR. Subcutaneous methotrexate versus oral form for the treatment and prophylaxis of chronic plaque psoriasis. Dermatol Ther. 2019;32(5):e13051.
Harten P. Folsäure zur Reduktion der Methotrexat-Toxizität [Reducing toxicity of methotrexate with folic acid]. Z Rheumatol. 2005;64(5):353-8.
Baran W, Batycka-Baran A, Zychowska M, Bieniek A, Szepietowski JC. Folate supplementation reduces the side effects of methotrexate therapy for psoriasis. Expert Opin Drug Saf. 2014;13(8):1015-21.
van Huizen AM, Menting SP, Gyulai R, Iversen L, van der Kraaij GE, Middelkamp-Hup MA, et al. International edelphi study to reach consensus on the methotrexate dosing regimen in patients with psoriasis. JAMA Dermatol. 2022;158(5):561-72.
Arnold T, Schaarschmidt ML, Herr R, Fischer JE, Goerdt S, Peitsch WK. Drug survival rates and reasons for drug discontinuation in psoriasis. J Dtsch Dermatol Ges. 2016;14(11):1089-99.
Due E, Blomberg M, Skov L, Zachariae C. Discontinuation of methotrexate in psoriasis. Acta Derm Venereol. 2012;92(4):353-4.
Dávila-Seijo P, Dauden E, Carretero G, Ferrandiz C, Vanaclocha F, Gómez-García FJ, et al. Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis. J Eur Acad Dermatol Venereol. 2016;30(11):1942-50.
Sherbini AA, Gwinnutt JM, Hyrich KL, RAMS Co-Investigators, SMM V. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022;61(10):3930-8.
Sherbini AA, Sharma SD, Gwinnutt JM, Hyrich KL, Verstappen SMM. Prevalence and predictors of adverse events with methotrexate mono- and combination-therapy for rheumatoid arthritis: a systematic review. Rheumatology (Oxford). 2021;60(9):4001-17.
Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68(7):1100-4.
Gligora M, Arzensek J, Rems D, Troskot N, Banjanin M. Psoriasis in the third age. Acta Derm Venereol Suppl (Stockh). 1989;146:168-70.
Pirro F, Caldarola G, Chiricozzi A, Burlando M, Mariani M, Parodi A, et al. Impact of body mass index on the efficacy of biological therapies in patients with psoriasis: a real-world study. Clin Drug Investig. 2021;41(10):917-25.
Pongparit K, Chularojanamontri L, Limphoka P, Silpa-Archa N, Wongpraparat C. Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: a retrospective cohort study. J Dermatol. 2018;45(5):540-5.