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. 2019 Jul 11;14(7):e0219539.
doi: 10.1371/journal.pone.0219539. eCollection 2019.

Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

Nini Kyvsgaard  1 , Torben Stamm Mikkelsen  1 , Mikael Thastum  2 , Anne Estmann Christensen  3 , Peder Skov Wehner  4 , Karsten Nysom  5 , Troels Herlin  1
Affiliations

Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

Nini Kyvsgaard et al. PLoS One. .

Abstract

Objectives: To analyse the internal consistency of an adaption of the methotrexate intolerance severity score (MISS); and to describe and compare the level of methotrexate intolerance evaluated by the MISS in Danish children with juvenile idiopathic arthritis (JIA) or acute lymphoblastic leukaemia (ALL), treated with low-dose methotrexate (MTX).

Methods: Cross-sectional study of children diagnosed with JIA or ALL, treated with low-dose MTX, aged 9 years or above, and cognitively intact. The patient's parents completed the MISS. MTX intolerance was defined as a total MISS score above 6.

Results: We enrolled 120 children with JIA and 23 children with ALL. The MISS had a good internal consistency in the JIA group. The median MISS score was higher in the JIA group than in the ALL group (JIA: 8; ALL: 1; p<0.0001); and the JIA group had a larger proportion of MTX intolerant children than the ALL group (JIA: 73/120; ALL: 4/23; p<0.001). Within both the JIA group and the ALL group, the MISS total score was not significantly correlated with age, MTX dose or the duration of low-dose MTX treatment.

Conclusion: In the JIA group the level of MTX intolerance was higher and more attributed to anticipatory, associative and behavioural symptoms than in the ALL group. The MISS may help to uncover whether MTX intolerance is present and which aspects are affected in the individual patient, thus guiding intervention. The MISS may also be applicable within leukaemia care.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The juvenile idiopathic arthritis study population.
Flowchart showing the enrolment and exclusion of patients within the juvenile idiopathic arthritis (JIA) study population. MTX; low-dose methotrexate. MISS; Methotrexate intolerance severity score. PGAmtx; Physician’s global assessment of MTX intolerance.
Fig 2
Fig 2. The acute lymphoblastic leukaemia study population.
Flowchart showing the enrolment and exclusion of patients within the acute lymphoblastic leukaemia (ALL) study population. NOPHO = Nordic Society of Paediatric Haematology and Oncology. MTX = low-dose methotrexate; MISS; Methotrexate intolerance severity score. PGAmtx; Physician’s global assessment of MTX intolerance.
Fig 3
Fig 3. The methotrexate intolerance severity score–the juvenile idiopathic arthritis group and the acute lymphoblastic leukaemia group.
Bar chart illustrating the mean scores (with 95% confidence interval) for each of the 12 items of the methotrexate intolerance severity score (MISS) for the juvenile idiopathic arthritis (JIA) group (n = 120) and the acute lymphoblastic leukaemia (ALL) group (n = 23).
See this image and copyright information in PMC

References

    1. 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. April 16;326(16):1043–1049. 10.1056/NEJM199204163261602 - DOI - PubMed
    1. Hashkes PJ, Laxer RM. Medical treatment of juvenile idiopathic arthritis. JAMA 2005. October 5;294(13):1671–1684. - PubMed
    1. 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. April;63(4):465–482. - PMC - PubMed
    1. Toft N, Birgens H, Abrahamsson J, Bernell P, Griskevicius L, Hallbook H, et al. Risk group assignment differs for children and adults 1–45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol. Eur J Haematol 2013. May;90(5):404–412. 10.1111/ejh.12097 - DOI - PubMed
    1. 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. May-Jun;25(3):480–485. - PubMed

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