Rheumatoid arthritis

Initial methotrexate dose makes no difference to outcomes: study

There appears to be no benefit from starting newly diagnosed patients with rheumatoid arthritis on high dose methotrexate (≥15mg/week) compared to low dose (≤10mg/week) as either monotherapy or in combination with other agents.

This is despite evidence that initiating doses appear to have increased over time, according to a study of DMARD-naïve patients from the international METEOR database.

The observational study involved 523 patients on methotrexate monotherapy, 266 on methotrexate plus a conventional synthetic DMARD and 615 on methotrexate plus oral glucocorticoids. Only 11 patients were started on methotrexate and a biologic and were therefore excluded from the analysis.

The study found no indication of improved clinical efficacy with high dose methotrexate over low dose via measures of disease activity (DAS and DAS28) or physical functioning (HAQ) after three to six months on treatment.

Commenting on the study, Australian Rheumatology Association (ARA) president Professor Rachelle Buchbinder told the limbic lower initiating doses of methotrexate might increase tolerability and reduce side effects.

“The bottom line from the study suggests that it doesn’t matter whether or not you start with lower or higher doses of methotrexate the outcomes are similar, suggesting that you can start with lower doses irrespective of whether you start it by itself or in combination with other DMARDs and/or glucocorticoids.”

However, the observational nature of the study and potential biases suggested the findings were unlikely to lead to a change in management.

“These data do not support the latest RA treatment guidelines from EULAR which suggest starting with methotrexate monotherapy at 15 mg/week orally, and escalating by 5 mg/month to 25–30 mg/week or the highest tolerable dose.”

Professor Buchbinder said 40 to 50% of people in the METEOR database already had erosions when they were first started on DMARDs.

“This shows that there is still a large delay. I would hope and think that this rate is much lower in Australia but I don’t know for sure so these data may or may not be applicable here.”

She noted the wide variety of prescribing patterns seen in the study and suggested that conflicting data and guideline changes worked against a more standard approach.

The study identified low dose methotrexate was by far the most common approach until about 2012 but was now prescribed about as often as high initiating doses.

Professor Buchbinder added that the ARA are working with the National Prescribing Service to increase public, GP and pharmacy understanding about the role of methotrexate in the treatment of rheumatoid arthritis.


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