Battle of the monotherapies: etanercept vs methotrexate

3 minute read

More RA patients who dropped methotrexate maintained remission than those who cut etanercept, but cessation is not recommended, expert says.

Rheumatoid arthritis (RA) patients in remission on methotrexate plus etanercept combination therapy may be more likely to maintain remission by moving to etanercept rather than methotrexate monotherapy, according to a new study funded by the biologic’s sponsor Amgen Inc.

“Patients with rheumatoid arthritis achieving remission on methotrexate plus etanercept therapy (Combo) face ongoing medication burden,” the authors wrote in Arthritis and Rheumatology.

The EULAR guidelines recommend carefully tapering – though not stopping all – therapy for patients in remission, noted the team, led by the University of Alabama at Birmingham in the US.

However, there was not enough research into whether remission could be maintained after discontinuing either one of the two drugs studied, they said.

They ran a multicentre double-blind randomised controlled trial involving adult RA patients who had achieved remission according to the Simplified Disease Activity Index (SDAI) after 24 weeks of combination therapy (10-25 mg of methotrexate and 50 mg of etanercept per week).

For 48 weeks, 51 patients were then randomised to continue the combination therapy, while 101 patients received oral methotrexate and a subcutaneous placebo, and 101 received subcutaneous etanercept plus oral placebo.

Almost half the etanercept monotherapy patients (49.5%) maintained remission, compared to 28.7% of methotrexate patients. Almost 53% of patients in the combination group maintained remission.

Most patients (70-80%) who had disease worsening and required rescue therapy recaptured remission, and there was no difference between the three groups in the overall time to recapturing remission.

The authors said the findings could provide guidance for clinicians and patients, particularly those worried about adverse events from methotrexate such as fatigue and nausea, and safety concerns around its long-term use.

While their study did not address gradual drug tapering, “simply reducing therapy may not lessen the long-term safety concerns and need for monitoring,” they said.

“The treatment-withdrawal design in the setting of sustained stringent remission does provide a ‘best case’ scenario for patients who are considering reducing therapy.”

Professor Susanna Proudman, rheumatologist and director of the Rheumatology Unit at the Royal Adelaide Hospital, noted that the EULAR guidelines suggest first tapering biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) rather than conventional synthetic DMARDs such as methotrexate “for cost and safety reasons”. However, that was in the absence of data to the contrary.

“Cost to patients is not really relevant in Australia as these drugs are all PBS-funded so the script price is standardised,” said Professor Proudman.

The Australian ‘living guidelines’ for inflammatory rheumatic diseases are still under development, but also include a weak recommendation for stepwise reduction of bDMARD/tsDMARD for RA patients who have achieved low disease activity or remission for at least six months, she noted.

The reduction can be continued until cessation but abrupt cessation is not recommended.

Professor Proudman said that in practice, some patients withdraw methotrexate themselves, with or without their rheumatologist’s knowledge, if they perceive they have good disease control on a bDMARD.

But there are some instances where methotrexate is mandated, or at least recommended in combination with the bDMARD, to prevent secondary failure due to antibodies developing to the bDMARD.

Although this study found continuing the bDMARD was associated with a more sustained remission than maintaining methotrexate, Professor Proudman emphasised that complete cessation is generally considered to have a high rate of relapse.

“A partial or more staggered withdrawal may be more successful,” she said.

“The key seems to be ensuring the patient is in sustained remission and not just low disease activity, otherwise the risk of relapse is higher.”

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