Comparison of Incidence of Adverse Events in Oral versus Injectable Methotrexate Therapy


C Nolan, S Maguire, P Dreelan, U Martin, C Sheehy


Department of Rheumatology, University Hospital Waterford


Methotrexate(MTX) is one of the most commonly used disease modifying anti-rheumatic drugs (DMARD) currently in use. Its efficacy and safety has been well documented over the years in numerous autoimmune mediated inflammatory conditions. The 2015 American College of Rheumatology(ACR) guidelines on the management of rheumatoid arthritis recommend methotrexate as the preferred DMARD when initiating treatment. The incidence of side effects can limit use of MTX and in some cases require discontinuation. Subcutaneous MTX has been previously proposed as an option to circumvent this issue.


To compare patient experiences and side effect profile with MTX in tablet form and as a subcutaneous injection in our patient population.


An opt-in survey was carried out on all patients on Methotrexate attending the Rheumatology Outpatient Clinics and Infusion Room in University Hospital Waterford during a two-month period. The survey was constructed of ten questions which included duration of treatment, MTX dosage, MTX route (oral vs s/c) along with the frequency and severity of adverse effects. These were evaluated under the headings of nausea, mouth ulcers, hair loss, fatigue, headaches and metallic aftertaste. In patients experiencing adverse effects answers were recorded as a value between 1 to 10 to reflect frequency and severity. In total 49 patients participated in the survey and are included in the below calculations.


In the studied population, 34 patients were on oral MTX while 18 patients were on subcutaneous MTX. The average duration of therapy on oral MTX was 161.9 months versus 36.4 months on subcutaneous. The incidence and severity of all studied side effects was found to be lower in patients on subcutaneous MTX, except for nausea which was high across both patient groups(figure 1).


The audit has shown that subcutanous methotrexate is overall better tolerated in our clinical practice. At present it is reserved for patients with issues tolerating oral MTX, this review would propose considering subcutaneous MTX as first line in certain patient populations.