Rheumatology Advance Access originally published online on December 3, 2007
Rheumatology 2008 47(2):222; doi:10.1093/rheumatology/kem306
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LETTERS TO THE EDITOR |
Use of parenteral methotrexate significantly reduces the need for biological therapy
Department of Rheumatology, Maidstone Hospital, Maidstone ME16 9QQ, UK
Correspondence to: A. Bharadwaj. E-mail: Anurag.Bharadwaj{at}nhs.net
SIR, According to current British Society for Rheumatology (BSR) guidelines, a patient with rheumatoid arthritis is entitled to receive anti-TNF therapy if the patient has failed on two DMARDs including methotrexate (MTX), and has a disease activity score (DAS) score more than 5.1 [1]. These guidelines have been introduced because of significant cost implications of biological treatment. The current guidelines do not specify the route of MTX administration. Addition of parenteral MTX in the BSR guidelines before anti-TNF therapy could have significant therapeutic and economic benefit. The current study was undertaken to analyse if the patients who qualify for anti-TNF therapy for the treatment of rheumatoid arthritis can derive additional benefit by switching over to parenteral MTX.
A retrospective analysis was performed of the records for 150 patients with rheumatoid arthritis on parenteral MTX, who attended the Rheumatology Department at Maidstone Hospital in Kent, UK, from 2000 to 2006. Thirty-two patients were included in the study, who had a DAS28 score recorded before and at least 3 months after receiving parenteral MTX. These patients did not have any other treatment altered apart from MTX. The age of the patients ranged from 28 to 78 yrs [median 61 yrs, interquartile range (IQR) 45–65]. The duration of disease ranged from 1 to 26 yrs (median 4 yrs IQR 3–6). Ten patients (32.2%) had erosive disease. Eighteen patients could not tolerate the oral MTX due to GI toxicity and 14 had suboptimal response to MTX. The dose of parenteral MTX varied from 7.5 mg/week to 25 mg/week. All patients received folic acid at the dose of 15 mg/week. The patients received MTX treatment for a median duration of 12 months (range 3–72 months).
There was significant improvement in the DAS28 score of the whole cohort on treatment with parenteral MTX. The subgroup analysis is shown in Table 1. Mainly, the 16 patients who were eligible to receive anti-TNF agents initially were not eligible after a median of 12 months of MTX treatment and five of them actually achieved remission by European League Against Rheumatism (EULAR) criteria. None of the patients showed any major adverse event requiring withdrawal of therapy.
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The update of the BSR guidelines [2] acknowledged the fact that the recommendations for the use of anti-TNF agents cannot remain static but must be adjusted as per the new information. In the BSR working group for the biological register, a suggestion to include parenteral MTX was initially rejected because of the lack of widespread experience of this therapy [3]. There are also concerns regarding the technical issues such as teaching patients self-injection techniques, monitoring and the costs involved. It is clear in the current economic environment that maintaining a patient on parenteral MTX has huge economic advantage over biological agents. The injection services, nurse-led clinics and monitoring clinics that are already in place for biological therapy can be utilized for MTX therapy by injection. Other reports have also shown that many of the patients who have failed on oral MTX may still respond to parenteral MTX [4–6]. Ours is probably the first report which has used the DAS28 score and the EULAR response criteria to show the benefit of using parenteral MTX. There are studies that have shown higher bioavailability and better clinical efficacy of parenteral MTX [7].
To conclude, we feel that utilization of parenteral MTX appears to improve disease control in MTX-intolerant or unresponsive patients with rheumatoid arthritis and may obviate the necessity for anti-TNF-
treatment in this group.
Disclosure statement: The authors have declared no conflicts of interest.
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[Free Full Text] - Deighton CM, George E, Kiely PDW, Ledingham J, Luqmani RA, Scott DGI. Updating the British Society for Rheumatology guidelines for anti-tumour necrosis factor therapy in adult rheumatoid arthritis (again). Rheumatology (2006) 45:649–52.
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[Abstract/Free Full Text] - Hoekstra M, Haagsma C, Neef C, Proost J, et al. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis. J Rheumatol (2004) 31:645–8.
[Abstract/Free Full Text]
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  C. Thornton, V. Ong, J. Ward, N. Kennedy, and A. Steuer Comment on: Use of parenteral methotrexate significantly reduces the need for biological therapy Rheumatology, September 1, 2008; 47(9): 1438 - 1438. [Full Text] [PDF]
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