Rheumatoid arthritis

Predictors of MTX failure allow selection of patients for early combination therapy

A UK study has identified which patients are likely to be unresponsive to methotrexate and may be suitable for early combination therapy.

Younger adult patients with early inflammatory polyarthritis, those who are RF positive and who have higher disease activity at baseline are more likely to fail MTX treatment early due to inefficacy.

The findings from the UK’s Norfolk Arthritis Register (NOAR) study suggest these patients may require combination therapy as a first-line treatment.

The study of 431 patients, who commenced methotrexate as their first DMARD between 2000 and 2008, found 33% failed treatment due to inefficacy and 16% due to adverse events.

The probability of remaining on methotrexate at two years was 82% and 72% at five years overall and 85% and 77% respectively for a subgroup of patients who fulfilled ACR/EULAR RA classification criteria.

The authors acknowledged these rates were higher than other studies of both oral and subcutaneous methotrexate.

“The higher MTX persistence seen in the NOAR cohort may therefore be due to a more homogenous cohort of patients starting oral MTX as their first DMARD early within their disease onset,” they said.

While the association between high baseline disease activity and early methotrexate failure is consistent with other studies, they said evidence linking age and treatment inefficacy varied.

“It is not clear whether younger patients are genuinely less responsive to MTX or whether they are more likely than older patients to move onto combination DMARD therapy in order to achieve complete control of disease activity.”

The median time to a second-line DMARD was 514 days.

Gastrointestinal symptoms were the most frequent adverse event reported by 42% of patients who stopped treatment.

The study also found an association between RF negativity and earlier cessation of therapy due to development of an adverse event, which has not previously been described.

“One possible explanation for this observation is that patients who are seropositive and have higher disease activity may be more likely to persist with MTX despite gastrointestinal side effects compared to the seronegative cohort with lower disease activity.”

ARA president Professor Rachelle Buchbinder told the limbic similar research in Australia some years ago found lower methotrexate retention rates than the UK study.

“We found that older age (greater than 65 years) was associated with higher rates of toxicity. But this was right at the beginning of use of MTX so we are much more familiar with the drug now and may not stop it as readily as we did then.”

She said there was likely a large variation in practice in how people commence DMARDs in Australia.

“Many people might use combination therapy early on with a view to switching to biologic drugs sooner if needed.”

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