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Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis

Maja Bulatović Ćalasan1*, Oscar FC van den Bosch1, Marjonne CW Creemers2, Martijn Custers3, Antonius HM Heurkens4, Jan Maarten van Woerkom5 and Nico M Wulffraat1

Author Affiliations

1 Department of Pediatric Immunology, Room KC 03.063.0, University Medical Center, Wilhelmina Children’s Hospital, Utrecht 3508 AB, The Netherlands

2 Department of Rheumatology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

3 Department of Rheumatology, Woerden, Maartenskliniek, The Netherlands

4 Department of Rheumatology, Meander Medical Center, Amersfoort, The Netherlands

5 Department of Rheumatology, Gelre Hospitals, Apeldoorn and Zutphen, The Netherlands

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Arthritis Research & Therapy 2013, 15:R217  doi:10.1186/ar4413

Published: 18 December 2013



The aim of this study was to determine the prevalence of gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) and after methotrexate (MTX) administration, termed MTX intolerance, in rheumatoid (RA) and psoriatic arthritis (PsA).


Methotrexate Intolerance Severity Score (MISS), previously validated in juvenile idiopathic arthritis patients, was used to determine MTX intolerance prevalence in 291 RA/PsA patients. The MISS consisted of four domains: abdominal pain, nausea, vomiting and behavioural symptoms, occurring upon, prior to (anticipatory) and when thinking of MTX (associative). MTX intolerance was defined as ≥6 on the MISS with ≥1 point on anticipatory and/or associative and/or behavioural items.


A total of 123 patients (42.3%) experienced at least one gastrointestinal adverse effect. The prevalence of MTX intolerance was 11%. MTX intolerance prevalence was higher in patients on parenteral (20.6%) than on oral MTX (6.2%) (p < 0.001).


Besides well-known gastrointestinal symptoms after MTX, RA and PsA patients experienced these symptoms also before MTX intake. RA and PsA patients on MTX should be closely monitored with the MISS for early detection of MTX intolerance, in order to intervene timely and avoid discontinuation of an effective treatment.