Tasa de retención de metotrexato en pacientes con artritis reumatoide y artritis psoriásica
Palabras clave:
metotrexato, artritis reumatoide, artritis psoriásica
Resumen
Introducción: el metotrexato (MTX) es una terapia de primera línea para la artritis reumatoide (AR) y la artritis psoriásica (APs). Se valora por su eficacia, bajo costo y facilidad de administración; sin embargo, los efectos adversos suelen llevar a la interrupción del tratamiento. Objetivos: determinar las causas de suspensión del MTX en pacientes con AR y APs. Materiales y métodos: se realizó un estudio retrospectivo que incluyó 148 pacientes (AR=102, APs=46) que recibieron MTX durante al menos un mes antes de su suspensión. Resultados: las principales razones para la suspensión del MTX en pacientes con AR y APs fueron intolerancia gástrica: 71,5% (AR) vs. 45,6% (APs) (p=0,002); toxicidad hepática: 4,9% (AR) vs. 17,3% (APs) (p=0,02); falla del tratamiento: 8,8% (AR) vs. 15,2% (APs) (p=0,24). La mediana de uso del MTX fue de 60 meses en la AR y de 24 meses en la APs (p<0,0001). Ni la vía de administración, el índice de masa corporal, la edad ni el sexo influyeron en la duración del tratamiento. Conclusiones: la intolerancia gástrica fue la principal causa de suspensión del MTX, especialmente en pacientes con AR. Además, la toxicidad hepática fue más frecuente en la APs. Aunque el uso de MTX fue más prolongado en la AR, los datos epidemiológicos y antropométricos no se asociaron con la suspensión del fármaco.Citas
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XX. Schmidt S, Messner CJ, Gaiser C, Hämmerli C, Suter-Dick L. Methotrexate-induced liver injury is associated with oxidative stress, impaired mitochondrial respiration, and endoplasmic reticulum stress in vitro. Int J Mol Sci. 2022 Dec 1;23(23):15116. doi: 10.3390/ijms232315116.
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XXII. Furst DE, Koehnke R, Burmeister LF, Kohler J, Cargill I. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol. 1989 Mar;16(3):313-320. PMID: 2724250.
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XXV. Perrotta FM, Ambrosino P, Lubrano E. Long-term survival of methotrexate as first-line therapy in rheumatoid arthritis, psoriatic arthritis and undifferentiated arthritis. J Clin Med. 2024 Dec;13(24):7540. doi: 10.3390/jcm13247540.
26. Albrecht K, Richter A, Callhoff J, et al. Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases. Arthritis Res Ther. 2016 Jun 23:18:149. doi: 10.1186/s13075-016-1043-9.
27. Schwarz CW, Loft N, Andersen V, Juul L, Zachariae C, Skov L. Are systemic corticosteroids causing psoriasis flare-ups? Questionnaire for Danish dermatologists, gastroenterologists and rheumatologists. Dermatology. 2021;237(4):588-594. doi: 10.1159/000510712.
II. Mustafa SH, Ahmad T, Balouch M, Iqbal F, Durrani T. Safety profile of methotrexate therapy in patients with rheumatoid arthritis. Cureus. 2022 Jul;14(7):e27047. doi: 10.7759/cureus.27047.
III. Nikiphorou E, Negoescu A, Fitzpatrick JD, et al. Indispensable or intolerable? Methotrexate in patients with rheumatoid and psoriatic arthritis: a retrospective review of discontinuation rates from a large UK cohort. Clin Rheumatol. 2014 May;33(5):609-14. doi: 10.1007/s10067-014-2546-x.
IV. Fatimah N, Salim B, Nasim A, Hussain K, Gul H, Niazi S. Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire). Clin Rheumatol. 2016 May;35(5):1341-1345. doi 10.1007/s10067-016-3243-8.
V. Amaral JM, Brito MJM, Kakehasi AM. Cultural adaptation and validation of the methotrexate intolerance severity score in Brazilian Portuguese for adults with rheumatoid arthritis. J Clin Rheumatol. 2021 Sep;27(6S):S168-S172. doi: 10.1097/RHU.0000000000001221.
VI. Londe AC, de Amorim JC, Julio PR, Wulffraat NM, Marini R, Appenzeller S. Cross-cultural adaptation and validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for children and adolescents with juvenile idiopathic arthritis. J Clin Med. 2023 Jan;12(3):1116. doi: 10.3390/jcm12031116.
VII. Braun J, Kästner P, Flaxenberg P, et al. 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. 2008 Jan;58(1):73-81. doi: 10.1002/art.23144.
VIII. Branco J, Barcelos A, de Araujo FP, et al. Utilization of subcutaneous methotrexate in rheumatoid arthritis patients after failure or intolerance to oral methotrexate: a multicenter cohort study. Adv Ther. 2016 Jan;33 (1):46-57. doi 10.1007/s12315-015-0276-3.
IX. Davis LA, Polk B, Mann A, Wolff RK, et al. Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis. Clin Exp Rheumatol. 2014 May;32(3):324-332.PMID: 24447348.
X. Shao W, Yuan Y, Li Y. Association between MTHFR C677T polymorphism and methotrexate treatment outcome in rheumatoid arthritis patients: a systematic review and meta-analysis. Genet Test Mol Biomarkers. 2017 May;21(5):275-285. doi: 10.1089/gtmb.2016.0326.
XI. Lie E, van der Heijde D, Uhlig T, Heiberg MS, et al. Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2010 Apr;69(4):671. doi: 10.1136/ard.2009.113308.
XII. Karpa V, Kalinderi K, Fidani L, Tragiannidis A. Association of microRNA Polymorphisms with toxicities induced by methotrexate in children with acute lymphoblastic leukemia. Hematol Rep. 2023 Nov;15(4):634-650. doi: 10.3390/hematolrep15040065.
XIII. Treviño LR, Shimasaki N, Yang W, et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol. 2009 Dec;27(35):5972-8. doi: 10.1200/JCO.2008.20.4156.
XIV. Ohta R, Mishiro T, Horinishi Y, Sano C. Multiple ulcers in the ileum and lymphadenopathy following the usage of methotrexate in a patient with rheumatoid arthritis: a case report. Cureus. 2024 Feb;16(2):e53406. doi: 10.7759/cureus.53406.
XV. Shea B, Swinden MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013 May;2013(5):CD000951. doi: 10.1002/14651858.CD000951.pub2.
XVI. Davis LA, Polk B, Mann A, et al. Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis. Clin Exp Rheumatol. 2014 May-Jun;32(3):324-332. PMID: 24447348
XVII. Shao W, Yuan Y, Li Y. Association between MTHFR C677T polymorphism and methotrexate treatment outcome in rheumatoid arthritis patients: a systematic review and meta-analysis. Genet Test Mol Biomarkers. 2017 May;21(5):275-285. doi: 10.1089/gtmb.2016.0326.
XVIII. Schmajuk G, Miao Y, Yazdany J, Boscardin WJ, Daikh DI, Steinman MA. Identification of risk factors for elevated transaminases in methotrexate users through an electronic health record. Arthritis Care Res. 2014 Aug;66(8):1159-66. doi: 10.1002/acr.22294.
XIX. Conway C, Cobice D, Gibson DS. Clinical and laboratory associations with methotrexate metabolism gene polymorphisms in rheumatoid arthritis. J Pers Med. 2020 Sep;10(4):149. doi: 10.3390/jpm10040149.
XX. Schmidt S, Messner CJ, Gaiser C, Hämmerli C, Suter-Dick L. Methotrexate-induced liver injury is associated with oxidative stress, impaired mitochondrial respiration, and endoplasmic reticulum stress in vitro. Int J Mol Sci. 2022 Dec 1;23(23):15116. doi: 10.3390/ijms232315116.
XXI. Branco J, Barcelos A, de Araujo FP, et al. Utilization of Subcutaneous methotrexate in rheumatoid arthritis patients after failure or intolerance to oral methotrexate: a multicenter cohort study. Adv Ther. 2016;33:46-57. doi 10.1007/s12315-015-0276-3.
XXII. Furst DE, Koehnke R, Burmeister LF, Kohler J, Cargill I. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol. 1989 Mar;16(3):313-320. PMID: 2724250.
XXIII. Schnabel A, Reinhold-Keller E, Willmann V, Gross WL. Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis. Rheumatol Int. 1994 Jun;14 (1) :33-38. doi: 10.1007/BF00302669.
XXIV. Lin M, Guo R, Su Z, Ke S, Zeng D. Combination leflunomide and methotrexate impedes the recovery of liver fibrosis, partly through inhibition of myeloid cell admittance. Mol Med Rep. 2019 Mar;19(3):1622-1628. doi: 10.3892/mmr.2019.9821.
XXV. Perrotta FM, Ambrosino P, Lubrano E. Long-term survival of methotrexate as first-line therapy in rheumatoid arthritis, psoriatic arthritis and undifferentiated arthritis. J Clin Med. 2024 Dec;13(24):7540. doi: 10.3390/jcm13247540.
26. Albrecht K, Richter A, Callhoff J, et al. Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases. Arthritis Res Ther. 2016 Jun 23:18:149. doi: 10.1186/s13075-016-1043-9.
27. Schwarz CW, Loft N, Andersen V, Juul L, Zachariae C, Skov L. Are systemic corticosteroids causing psoriasis flare-ups? Questionnaire for Danish dermatologists, gastroenterologists and rheumatologists. Dermatology. 2021;237(4):588-594. doi: 10.1159/000510712.
Publicado
2025-09-22
Cómo citar
1.
Collere Melara A, Ishisak VI, Skare TL, Beckhauser AP, Kahlow BS. Tasa de retención de metotrexato en pacientes con artritis reumatoide y artritis psoriásica. Rev. Argent. Reumatol. [Internet]. 22 de septiembre de 2025 [citado 27 de octubre de 2025];36(2). Disponible en: https://ojs.reumatologia.org.ar/index.php/revistaSAR/article/view/961
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Artículo Original
