Faster is not always better with MTX

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A new study shows no benefit in fast escalation of methotrexate treatment for rheumatoid arthritis patients.

A new study conducted in India has shown no benefit in fast escalation of methotrexate treatment for rheumatoid arthritis patients.

The multicentre randomised controlled trial, published in Annals of the Rheumatic Diseases, found that the “fast” escalation of 5mg every fortnight, starting at 15mg, had no extra benefit compared to a “usual” dose escalation of 5mg every month up to a maximum of 25mg.

Until now, there have been no head-to-head trials comparing escalation strategies, and there was a large degree of variability in how patients were treated, the authors said.

“The results from this study suggest that ‘faster is not always better’ in the context of MTX escalation in RA,” said the study authors.

Researchers randomly assigned almost 180 adults with rheumatoid arthritis to either receive a fast escalation of MTX, as recommended by the 3E initiative and EULAR, or to have their dose escalated more slowly.

Patients were MTX-naïve, or off MTX for at least 6 months, and could be on low-dose prednisolone and/or hydroxychloroquine but not taking other DMARDs. The mean DAS28-CRP at baseline was 5.4.

All participants started oral MTX at 15mg per week, and the fast escalation group escalated by 5mg every two weeks, while the usual escalation group increased at a rate of 5mg every four weeks. 

The primary outcome was proportion of patients at 16 weeks with a good response based on EULAR response criteria – that is, DAS28-CRP ≤3.2 and an improvement of >1.2.

At 16 weeks, around 28% of the usual escalation group achieved a good response compared to 22.5% of the fast escalation group, a non-significant difference.

The mean DAS28-CRP was similar for the two groups at both 8 and 16 weeks. Responses were similar even after an extended follow-up at six months. There were no differences between the two groups in health assessment questionnaire (HAQ) or MTX polyglutamates at 8 or 16 weeks.

There were no significant differences in the tolerability or safety of the different dosage strategies, although there were initially more gastrointestinal adverse events reported in the fast escalation group.

Because MTX is the gold standard treatment for rheumatoid arthritis, it was important to have strong evidence to guide dosing strategy, said the authors, especially for developing countries given its low cost.

But Hobart rheumatologist Professor Graeme Jones, of the Menzies Institute for Medical Research, said that the doses used in the study were higher than many Australian rheumatologists would use.

“They started everyone quite high, on 15mg, but after 15mg orally the body doesn’t absorb very much,” he said.

“Most Australian rheumatologists are probably still very conservative, starting at 7.5mg to 10mg and building up,” he added. “Personally, I won’t go above 20mg orally because I see absolutely no point of doing that – the body just doesn’t absorb any more.”

Ann Rheum Dis 2021, online 12 October

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