To the Editor:
Methotrexate (MTX) is widely used as the drug of choice in the treatment of rheumatoid arthritis (RA) and it is advocated as such by the British Society for Rheumatology guidelines1. To date, oral MTX has been used because of patient preference for its once-weekly dosing regime and low costs. Tumor necrosis factor-α inhibitors (anti-TNF-α) have become increasingly popular in treating RA2. However, anti-TNF-α drugs are expensive and have been shown to increase the risk of skin and soft tissue infections and reactivation of tuberculosis and possibly malignancy3.
MTX is currently available for oral or parenteral administration. Although current guidelines encourage use of MTX as first-line therapy, they do not specify the route of administration1,4. Several studies describe the increased efficacy5, tolerability6, and bioavailability7,8 of subcutaneous (SC) MTX compared with oral MTX. It is possible that patients may be successfully treated with SC MTX where oral MTX has failed, preventing the need for biologic therapy.
We carried out a retrospective analysis of records of 301 patients with RA at Gartnavel General Hospital, Glasgow, to determine the possible financial and health benefits of using SC MTX before resorting to anti-TNF-α therapy. From our cohort, a total of 256 patients had tried anti-TNF-α therapy and 68 had had SC MTX.
Most patients had switched to SC from oral MTX because it was ineffective or intolerable because of adverse effects. Of the 68 patients who had tried SC MTX, 29% had subsequently discontinued treatment, mostly as a result of adverse effects. Of the remaining patients still on SC MTX, 22% were also on anti-TNF-α therapy, while 49% were established with stable disease taking SC MTX alone. Therefore, we can take 49% as the success rate of SC MTX in our cohort.
One year of anti-TNF-α therapy for a single patient costs £9295 on average, while the equivalent dosage of SC MTX costs £927.68. Therefore, if a patient commenced SC MTX instead of anti-TNF-α therapy it would result in potential savings of £8367.32 per patient per year. Of the 256 patients with RA receiving anti-TNF-α therapy, 233 had never tried SC MTX. Using the success rate of 49%, we calculate that 114 of these patients may have been treated successfully with SC MTX alone, preventing the need for biologic therapy. This translates to an overall cost-saving per year of future treatment for this cohort of patients as follows: £8367.32 × 114 = £953,874.48. We can also retrospectively calculate the potential savings for each year since 2001, based on the number of new anti-TNF-α patients each year (Table 1).
We have demonstrated that expenditure for anti-TNF-α therapy has been increasing since 2001. This is a cause for concern, given the current financial climate and recent figures published by the UK National Audit Office9. In November 2009, the chief executive of the UK National Health Service (NHS) stated that “the NHS and the Department of Health would need to deliver between £15–£20 billion in efficiency savings per year by 2013/14”9. In our study alone almost £1 million could have been saved per year if the patients in our cohort had received SC MTX before they were moved to more expensive anti-TNF-α therapies. We recognize that our data are from a local cohort but our findings represent a sample of the 1% of the total population diagnosed with RA10. If, as we suspect, the under-use of SC MTX is a national trend, the potential savings to the NHS could be hundreds of millions of pounds. We also recognize that the 49% success rate is a gross estimate; however, even with a figure of 25% the savings would still be substantial. Therefore, if national guidelines stipulated that SC MTX be tried before anti-TNF-α therapy, this could not only increase financial savings markedly but also improve patient safety.