Background Methotrexate (MTX) has been used for many years as treatment for Rheumatoid Arthritis (RA), and remains the first line disease modifying therapy with a well established efficacy and safety profile. Side effects include gastrointestinal (GI) symptoms, deranged liver function, pneumonitis and bone marrow suppression. Subcutaneous (SC) MTX offers improved tolerability and bioavailability when compared to oral MTX1. Patients with GI disturbances from oral MTX are often switched to the SC route. Other reasons for switching include mucositis, malaise and lack of efficacy on the maximum oral dose. Although few randomised controlled trials of parenteral versus oral MTX exist, the majority suggests a benefit to switching from oral to parenteral MTX2. MTX acts as a dihydrofloate reducatase inhibitor and therefore macrocytosis is a well recognised side effect. Although Azathioprine may also lead to macrocytosis3 studies imply no link between this and overt bone marrow toxicity4 and similar conclusion have not been reached with MTX either via the oral or SC route. Objectives To determine whether MCV is affected by SC MTX in a cohort of RA patients in a district general hospital setting. Methods Twenty nine patients with RA on SC MTX were analysed. Inclusion criteria were diagnosis of RA and treatment with SC MTX. All patients were treated with supplemental oral folic acid. Data was collected for the time period spanning September 2009 to December 2013. Macrocytosis is defined as an MCV of 100 or greater on five consecutive readings, or more than 105 on three readings. Results The average duration of disease was 15.3 years. 9 of 29 (31%) patients on SC MTX demonstrated macrocytosis. Of these, 5 (17%) exhibited a higher than normal MCV on oral MTX before conversion to SC administration. Four (14%) became macrocytic on SC MTX, with a prior normal MCV on oral treatment. Of the 14% who showed macrocytosis on SC MTX the average Hb was 12.6g/dl. In the 20 patients who did not develop macrocytosis the average Hb was 12.4g/dl. Data were collected for potentially confounding factors such as vitamin B12 or folate deficiency, thyroid dysfunction and myeloma. Two of the fifteen patients who had raised MCV were found positive for one of these factors (low folate and high TSH). Conclusions Only 14% of patients developed macrocytosis after conversion from oral to SC MTX. There was little difference in Hb between the patients who were macrocytic and those who were not. No overt case of anaemia was identified. None developed severe manifestations of bone marrow failure such as sustained pancytopenia. Our data suggest patients on SC MTX do not have a greater propensity to develop macrocytosis, and even in those who do there was no concurrent anaemia. More research on the implication of macrocytosis and SC MTX therapy is needed. References Hoekstra et al. J Rheumatol. 2004 Apr;31(4):645-8. Moitra RK. Et al. 2005 Feb;44(2):256-7. Bernstein CNet al. DigDis Sci. 1994;39:1638–41 Thomas CW et al. Inflamm Bowel Dis. 2003;9:2...
Background Oral methotrexate (MTX) is frequently used in the treatment of patients with rheumatoid arthritis (RA). Subcutaneous (SC) MTX is increasingly being prescribed in clinical practice as an alternative since, at the same dose, it has been shown to be more efficacious than oral MTX1 and better tolerated.2,3 Patients who have switched from oral to SC MTX due to intolerance or lack of efficacy respond well,1 and have reported an improved quality of life.4 Routine use of SCMTX following oral MTX failure may also avoid the need for costly biologic therapy in selected patients.5 There are, however, few published data on the use of SCMTX in real-life clinical setting. Objectives To identify clinical outcomes of RA patients in the clinical context of a District General Hospital following a switch to SCMTX after failure of oral MTX. Methods RA patients who has received SCMTX at the Royal Surrey County Hospital, Guildford were identified from medical records. 103 patients were eligible for inclusion. Demographic data, reasons for switch from oral to SCMTX, continuation rates, biologic therapy, disease activity scores (DAS), swollen and tender joint counts (SJC and TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and visual analogue scale (VAS) scores were recorded. Results The average age for the diagnosis of RA in our cohort was 50 years. 79% of patients were female. Mean duration of oral therapy was 8.8 years, at a mean weekly dose of 20.3 mg (range 7.5-25.0 mg/week). 43% of all patients were on one DMARD and 12% on two DMARDs. Reasons for switching to SCMTX included lack of efficacy (45%) and intolerance/adverse events (27%). When switched 89 patients were receiving SCMTX without biologic (mean dose 20.8 mg/week); 14 patients (mean dose 18.4 mg/week) were already on a biologic. For the total cohort continuation rate at the end of year 1 was 94% and at the end of year 2 was 82%. Treatment continuation at the end of year 1 for patients on SCMTX alone was similar to that of patients on SCMTX and a biologic (94% vs.93%, respectively), but lower at the end of year 2 (77% vs. 92%, respectively). In total 9 patients discontinued SCMTX over the 2-year period due to adverse events (5), efficacy (1), other/unknown reason (3). DAS assessments at 3, 6 and 12 months showed continued DAS improvement over time and a rise in both significant improvements ΔDAS28 >1.2 and remission rates (DAS <2.6). Improvements in SJC, TJC, ESR, CRP levels and VAS scores were also seen over time. Conclusions Analysis of our audit suggest that there is added benefit of switching patients to SCMTX at the same dose, for those who fail to respond to or tolerate oral MTX. Patients responded well with high continuation rates after 1 and 2 years' therapy. Reductions in DAS and levels of remission, either with or without biologic therapy, were also seen. Based on these findings SCMTX could be considered as a routine before introducing a biologic agent. References Braun J, et al. Arthritis Rheum 2008;58:73-81. Rutko...
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