Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2017

Open Access 01-12-2017 | Review

Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis

Authors: Sonja Falvey, Lauren Shipman, Norman Ilowite, Timothy Beukelman

Published in: Pediatric Rheumatology | Issue 1/2017

Login to get access

Abstract

Background

Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients.

Main body

A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with methotrexate. Many strategies have been employed in attempts to reduce methotrexate-induced nausea, including folate supplementation, switching from oral to subcutaneous methotrexate, anti-emetic therapy, behavioral therapy, and others. Anticipatory nausea can be difficult to treat, making primary prevention of nausea with anti-emetics an attractive approach.

Conclusion

Understanding the prevalence and impact of methotrexate-induced nausea, as well as potentially effective interventions, may help maximize the therapeutic benefits of methotrexate.
Literature
1.
Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.PubMed
2.
Gowdie PJ, Tse SM. Juvenile idiopathic arthritis. Pediatr Clin N Am. 2012;59(2):301–27.CrossRef
3.
Giannini EH, Brewer EJ, Kuzmina N, Shaikov A, Maximov A, Vorontsov I, et al. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric rheumatology collaborative study group and the cooperative Children's study group. N Engl J Med. 1992;326(16):1043–9.CrossRefPubMed
4.
Woo P, Southwood TR, Prieur AM, Dore CJ, Grainger J, David J, et al. Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum. 2000;43(8):1849–57.CrossRefPubMed
5.
Klein A, Kaul I, Foeldvari I, Ganser G, Urban A, Horneff G. Efficacy and safety of oral and parenteral methotrexate therapy in children with juvenile idiopathic arthritis: an observational study with patients from the German Methotrexate registry. Arthritis Care Res (Hoboken). 2012;64(9):1349–56.CrossRef
6.
Ruperto N, Murray KJ, Gerloni V, Wulffraat N, de Oliveira SK, Falcini F, et al. A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum. 2004;50(7):2191–201.CrossRefPubMed
7.
Beukelman T, Ringold S, Davis TE, DeWitt EM, Pelajo CF, Weiss PF, et al. Disease-modifying antirheumatic drug use in the treatment of juvenile idiopathic arthritis: a cross-sectional analysis of the CARRA registry. J Rheumatol. 2012;39(9):1867–74.CrossRefPubMedPubMedCentral
8.
Mannion ML, Xie F, Curtis JR, Beukelman T. Recent trends in medication usage for the treatment of juvenile idiopathic arthritis and the influence of tumor necrosis factor inhibitors. J Rheumatol. 2014;41(10):2078–84.CrossRefPubMed
9.
Hashkes PJ, Becker ML, Cabral DA, Laxer RM, Paller AS, Rabinovich CE, et al. Methotrexate: new uses for an old drug. J Pediatr. 2014;164(2):231–6.CrossRefPubMed
10.
Patil P, Parker RA, Rawcliffe C, Olaleye A, Moore S, Daly N, et al. Methotrexate-induced nausea and vomiting in adolescent and young adult patients. Clin Rheumatol. 2014;33(3):403–7.CrossRefPubMed
11.
Bulatovic M, Heijstek MW, Verkaaik M, van Dijkhuizen EH, Armbrust W, Hoppenreijs EP, et al. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score. Arthritis Rheum. 2011;63(7):2007–13.CrossRefPubMed
12.
van Dijkhuizen EH, Bulatovic Calasan M, Pluijm SM, de Rotte MC, Vastert SJ, Kamphuis S, et al. Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study. Pediatr Rheumatol Online J. 2015;13:5.CrossRefPubMedPubMedCentral
13.
Mulligan K, Kassoumeri L, Etheridge A, Moncrieffe H, Wedderburn LR, Newman S. Mothers' reports of the difficulties that their children experience in taking methotrexate for juvenile idiopathic arthritis and how these impact on quality of life. Pediatr Rheumatol Online J. 2013;11(1):23.CrossRefPubMedPubMedCentral
14.
Amin TS, Shenton S, Mulligan K, Wedderburn LR, Wood M, VanRooyen V, et al. Strategies for the prevention and management of methotrexate-related nausea and vomiting in juvenile idiopathic arthritis: results of a UK paediatric rheumatology prescriber survey. Rheumatology (Oxford). 2015;54(11):2108–9.CrossRef
15.
Brunner HI, Johnson AL, Barron AC, Passo MH, Griffin TA, Graham TB, et al. Gastrointestinal symptoms and their association with health-related quality of life of children with juvenile rheumatoid arthritis: validation of a gastrointestinal symptom questionnaire. J Clin Rheumatol. 2005;11(4):194–204.CrossRefPubMed
16.
Foeldvari I, Wierk A. Effectiveness of leflunomide in patients with juvenile idiopathic arthritis in clinical practice. J Rheumatol. 2010;37(8):1763–7.CrossRefPubMed
17.
van der Meer A, Wulffraat NM, Prakken BJ, Gijsbers B, Rademaker CM, Sinnema G. Psychological side effects of MTX treatment in juvenile idiopathic arthritis: a pilot study. Clin Exp Rheumatol. 2007;25(3):480–5.PubMed
18.
Zoubek A, Kronberger M, Puschmann A, Gadner H. Ondansetron in the control of chemotherapy-induced and radiotherapy-induced emesis in children with malignancies. Anti-Cancer Drugs. 1993;4(Suppl 2):17–21.CrossRefPubMed
19.
Calasan MB, van den Bosch OF, Creemers MC, Custers M, Heurkens AH, van Woerkom JM, et al. Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis. Arthritis Res Ther. 2013;15(6):R217.CrossRefPubMed
20.
Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;5:CD000951.
21.
Ravelli A, Migliavacca D, Viola S, Ruperto N, Pistorio A, Martini A. Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis. Clin Exp Rheumatol. 1999;17(5):625–7.PubMed
22.
Alsufyani K, Ortiz-Alvarez O, Cabral DA, Tucker LB, Petty RE, Malleson PN. The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol. 2004;31(1):179–82.PubMed
23.
van Dijkhuizen EH, Pouw JN, Scheuern A, Hugle B, Hardt S, Ganser G, et al. Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study. Clin Exp Rheumatol. 2016;34(1):148–54.PubMed
24.
Culy CR, Bhana N, Plosker GL. Ondansetron: a review of its use as an antiemetic in children. Paediatr Drugs. 2001;3(6):441–79.CrossRefPubMed
25.
Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011;9:CD005506.
26.
Cheng A. Emergency department use of oral ondansetron for acute gastroenteritis-related vomiting in infants and children. Paediatr Child Health. 2011;16(3):177–82.PubMedPubMedCentral
27.
Kempinska A, Benchimol EI, Mack A, Barkey J, Boland M, Mack DR. Short-course ondansetron for the prevention of methotrexate-induced nausea in children with Crohn disease. J Pediatr Gastroenterol Nutr. 2011;53(4):389–93.PubMed
28.
Blanco R, Gonzalez-Gay MA, Garcia-Porrua C, Ibanez D, Garcia-Pais MJ, Sanchez-Andrade A, et al. Ondansetron prevents refractory and severe methotrexate-induced nausea in rheumatoid arthritis. Br J Rheumatol. 1998;37(5):590–2.CrossRefPubMed
29.
Lexicomp Online®, Pediatric & Neonatal Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; 2015.
30.
Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P, et al. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med. 2005;352(16):1655–66.CrossRefPubMed
31.
Benucci M, Saviola G, Manfredi M, Sarzi-Puttini P, Atzeni F. Cost effectiveness analysis of disease-modifying antirheumatic drugs in rheumatoid arthritis. A systematic review literature. Int J Rheumatol. 2011;2011:845496.CrossRefPubMedPubMedCentral
32.
Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011;63(4):465–82.CrossRef
Metadata
Title
Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis
Authors
Sonja Falvey
Lauren Shipman
Norman Ilowite
Timothy Beukelman
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2017
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-017-0180-2

Other articles of this Issue 1/2017

Pediatric Rheumatology 1/2017 Go to the issue

Research article

A national cohort study on pediatric Behçet’s disease: cross-sectional data from an Italian registry

Research article

Assessment of transition readiness in adolescents and young adults with chronic health conditions

Research article

Health-related quality of life among Swedish children with Juvenile Idiopathic Arthritis: parent–child discrepancies, gender differences and comparison with a European cohort

Research article

TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population

Research article

Patients with juvenile idiopathic arthritis in clinical remission with positive power Doppler signal in joint ultrasonography have an increased rate of clinical flare: a prospective study

Review

When a patient suspected with juvenile idiopathic arthritis turns out to be diagnosed with an infectious disease – a review of Lyme arthritis in children