Determinants for Drug Survival of Methotrexate in Patients with Psoriasis: 10-Years Retrospective Analysis of DERMA.PT Registry
Introduction: Methotrexate has been used in the systemic treatment of psoriasis since 1950 and remains a first-line drug. It is important to assess the factors that influence its discontinuation. The aim of the authors was to identify determinants of drug survival of metho- trexate in patients with psoriasis.
Methods: A retrospective analysis was performed concerning patients who started psoriasis treatment with methotrexate between January 2010 and January 2020 and were included in the national registry DERMA.PT by the Centro Hospitalar Universitário São João.
Results: A total of 146 patients with psoriasis treated with methotrexate alone or in combination with phototherapy were identified. Most were male (55%), with a mean age of 51±13 years and 65% had psoriasis for more than 10 years. Psoriasis vulgaris (49%) and psoriatic arthritis (47%) were the most common forms of psoriasis, with a mean initial PASI of 10.7±5.6. The majority of patients were methotrexate-naïve. In total, 66 (45%) patients discontinued treatment, with a mean survival time of 18.0±15.5 months. The most common reasons for discontinuation were ineffectiveness (32%), poor compliance (18%) and gastrointestinal intolerance (11%). Previous treatment with cyclosporine and the presence of psoriatic arthritis had both statistically significant associations with the discontinuation of methotrexate. In most cases, a switch to anti-TNFα monoclonal antibody was performed.
Discussion: In recent years, retrospective studies have been published focusing on the drug survival of methotrexate in psoriasis, ranging from 12 to 21 months. The main reasons for discontinuation were ineffectiveness and adverse effects, namely gastrointestinal. Our study is in line with what has been described but stands out for the high percentage of patients who maintained treatment. The tremendous evolution in the treatment of psoriasis over the 10-year period of the study greatly influenced the results. The main limitation of this analysis results from its re- trospective nature.
Conclusion: The results are in agreement with the published survival characteristics of methotrexate and reinforce its importance and role of this drug in the treatment of this disease.
- Smith JA, Wehausen B, Richardson I, Zhao Y, Li Y, Herrera V, et al. Treatment Changes in Pa-tients With Moderate to Severe Psoriasis: A Retrospective Chart Review. J Cutan Med Surg 2018;22:25-30. doi: 10.1177/1203475417724438.
- Due E, Blomberg M, Skov L, Zachariae C. Discontinuation of methotrexate in psoriasis. Acta Derm Venereol 2012; 92(4): 353-354. doi: 10.2340/00015555-1233.
- Levin AA, Gottlieb AB, Au S. A comparison of psoriasis drug failure rates and reasons for dis-continuation in biologics vs conventional systemic therapies. J Drugs Dermatol 2014; 13(7): 848-53. PMID: 25007369.
- Dogra S, Mahajan R. Systemic methotrexate therapy for psoriasis: past, present and future. Clin Exp Dermatol 2013;38:573-88. doi: 10.1111/ced.12062.
- Otero ME, van den Reek PA, van de Kerkhof CM, Mertens JS, Seyger MB, Kievit W et al. Be-liefs About Medicines in Patients with Psoriasis Treated with Methotrexate or Biologics: A Cross-sectional Survey Study. Acta Derm Venereol 2019;99:386-392. doi: 10.2340/000155553108.
- Marco D, Vincenzo G, Gianfranco A. Methotrexate: practical use in dermatology. G Ital Dermatol Venereol 2016;151:535-43. PMID: 26761767.
- Elmamoun M, Chandran V. Role of Methotrexate in the Management of Psoriatic Arthritis. Drugs 2018;78:611-619. doi: 10.1007/s40265-018-0898-2.
- Coates LC, Gossec L, Ramiro S, Mease P, van der Heijde D, Smolen JS et al. New GRAPPA and EULAR recommendations for the management of psoriatic arthritis. Rheumatology (Oxford) 2017;56:1251-1253. doi: 10.1093/rheumatology/kew390.
- Otero ME, van den Reek JM, Seyger MM, van de Kerkhof PC, Kievit W, de Jong EM. Determi-nants 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. doi: 10.1111/bjd.15305.
- Mason KJ, Williams S, Yiu ZN, McElhone K, Ashcroft DM, Kleyn CE et al. Persistence and effectiveness of nonbiologic systemic therapies for moderate-to-severe psoriasis in adults: a sys-tematic review. Br J Dermatol 2019;181:256-264. doi: 10.1111/bjd.17625.
- Dávila-Seijo P, Dauden E, Carretero G, Ferrandiz C, Vanaclocha F, Gómez-García F et al. Sur-vival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis. J Eur Acad Dermatol Venereol 2016; 30(11):1942-1950. doi: 10.1111/jdv.13682.
- 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. doi: 10.2340/00015555-2130.
- Wojciech B, Aleksandra BB, Magdalena Z, Andrzej B, Jacek CS. Folate supplementation re-duces the side effects of methotrexate therapy for psoriasis. Expert Opin Drug Saf 2014;13:1015-21. doi: 10.1517/14740338.2014.933805.
- Cline A, Jorizzo JL. Does daily folic acid supplementation reduce methotrexate efficacy? Dermatol Online J 2017 15;23:13030. PMID: 29447631.
- Busard Cl, Cohen AD, Wolf P, Gkalpakiotis S, Cazzaniga S, Stern RS et al. Biologics combined with conventional systemic agents or phototherapy for the treatment of psoriasis: real-life data from PSONET registries. J Eur Acad Dermatol Venereol 2017. doi: 10.1111/jdv.14583.
- 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: 640-7. doi: 10.1159/000452740.
- 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): 1089-1099. doi: 10.1111/ddg.13152.
- Mrowietz U, Elder JT, Barker J. The importance of disease associations and concomitant thera-py for the long-term management of psoriasis patients. Arch Dermatol Res 2006;298:309-19. doi: 10.1007/s00403-006-0707-8.
- Bronckers GJ, Paller AS, West DP, Lara-Corrales I, Tollefson MM, Tom WL et al. A Compari-son of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents. JAMA Dermatol 2020;156:384-392. doi: 10.1001/jamadermatol.2019.4835.
- Vollenbroek BO, Doggen JM, Janssens WA, Moens HJ. Dermatological guidelines for monitor-ing methotrexate treatment reduce drug-survival compared to rheumatological guidelines. PLoS One 2018;13:e0194401. doi: 10.1371/journal.pone.0194401.
- Shivani BK, Mark GL. Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80:43-53. doi: 10.1016/j.jaad.2018.06.056.
- Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff B, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019;80:1029-1072. doi: 10.1016/j.jaad.2018.11.057.
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