Article Text

AB0593 Subcutaneous methotrexate is more efficacious and better tolerated than oral methotrexate: The experience of a large group of patients in the rheumatology department of a district general hospital
  1. A. Liakos,
  2. M. Batley,
  3. T. Hammond,
  4. A. Saha,
  5. P. Shrestha,
  6. A. Keough
  1. Maidstone & Tunbridge Wells Nhs Trust, Maidstone, United Kingdom


Background With the emphasis in the management of inflammatory arthritis on early disease modification it is vital that prescribed treatments are tolerated and adhered to. Methotrexate can prove difficult for patients to sustain when taken orally, especially at high doses. To reduce side effects subcutaneous methotrexate has been suggested as a next step after oral therapy fails. It has been shown to be more efficacious at higher doses than oral therapy and to increase red blood cell methotrexate polyglutamate levels to concentrations significantly associated with reduced disease activity.

Objectives A large group of patients who were switched from oral to subcutaneous methotrexate was studied in order to chart whether this prompts better tolerance and greater efficacy as represented by the DAS28 score.

Methods A retrospective data collection was performed on patients switched from oral to subcutaneous methotrexate from 2003-2011. The reason for this switch was sought via patient notes and clinic letters. In those switched as part of local protocol to increment therapy the change in DAS28 score pre- and post-switch was studied; those with a diagnosis other than rheumatoid arthritis were excluded. In those switched for intolerance their tolerance post-switch was recorded.

Results In total 191 patients were switched from oral to subcutaneous methotrexate. Of these, 53 were switched due to intolerance. The other 138 were switched as part of local protocol to increment therapy. 51 of these were excluded due to insufficiently documented DAS28 scores or as their diagnosis was other than rheumatoid arthritis.

Of the 53 switched for intolerance (mean age 57.9, 72% female, 28% male, 81% rheumatoid arthritis, 19% others, mean dose 17.5mg) 40 (75.5%) tolerated the subcutaneous therapy.

In the incremental group of 87, all with rheumatoid arthritis, (mean age 59.5, 62% female, 38% male, 48% rheumatoid factor positive, mean dose 20.3mg, 6% already on biologic therapy, 7% started on biologic therapy concurrently) median DAS28 prior to switch was 5.34 (IQR =4.56-6.3) and six months after switch 4.26 (IQR =3.32-5.3) (p<0.001). In 33 cases DAS28 fell from >5.1 to <5.1. As per the EULAR criteria, 13 showed good response, 35 moderate and 39 no response.

Conclusions A large group of patients switched from oral to subcutaneous methotrexate over 8 years in a district general hospital was studied. In those switched due to intolerance, over 75% tolerated the subcutaneous preparation. In those switched as part of local protocol to increment therapy, an improvement in the median DAS28 score of 1.08 (p<0.001) after 6 months of subcutaneous therapy was demonstrated. This reinforces the suggestion that subcutaneous methotrexate should be used as the next step in treatment at the first sign of failure of oral methotrexate whether this failure be intolerance or lack of efficacy.

  1. Stamp LK et al, Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis, Journal of Rheumatology, 2011

  2. Braun J et al, Comparison of the clinical efficacy of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis, Arthritis Rheumatology 2008 Jan; 58(1): 73-81

Disclosure of Interest None Declared

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.