Etanercept monotherapy superior to methotrexate in RA remission maintenance
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In patients with rheumatoid arthritis who achieve remission with combination therapy and then withdraw either etanercept or methotrexate, monotherapy with the former is superior to the latter for remission maintenance, noted a speaker here.
“For those patients with RA who are in remission on combination therapy — for example, methotrexate — and a TNF inhibitor such as etanercept, it is not clear whether both therapies have to be continued indefinitely,” Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, told attendees at the virtual meeting. “For someone in their 40s or 50s, having to span both of these medicines for what might be years or even decades, might be a bit of a daunting prospect.”
“Both the American College of Rheumatology and the EULAR RA guidelines recommend to consider tapering RA medications, particularly in patients who are in persistent remission,” he added. “Probably it is not realistic to expect people to come off all RA therapies, but the idea that someone starting on two drugs — combination therapy — might be able to withdraw one of them, I think, would probably be attractive to many patients, as well as to clinicians. However, the optimal approach about how best to do that is not clear.
To compare the impact of withdrawing either methotrexate or etanercept (Enbrel, Amgen) on remission maintenance among patients with RA who achieved sustained remission with a combination of the two, Curtis and colleagues conducted the SEAM-RA trial. The researchers enrolled 371 adults receiving 50 mg of weekly etanercept alongside 10-25 mg of weekly methotrexate, and who met the ACR/EULAR RA remission criteria, for a 24-week, open-label period. After 24 weeks, the 253 who remained in remission entered a 48-week, double-blind period, in which they were randomized to receive either withdraw etanercept, withdraw methotrexate or continue both.
In all, the etanercept- and methotrexate-monotherapy groups each included 101 participants, while 51 remained with combination therapy. Participants whose disease worsened received combination rescue therapy — those in the combination arm continued with that regimen — and were deemed non-responders. The primary endpoint was the proportion of participants in SDAI remission without disease worsening at week 48 in the monotherapy groups.
Secondary endpoints included the proportion of those in SDAI remission without disease worsening at week 48 in the combination group compared with the methotrexate-monotherapy arm, the time to disease worsening and the time to recapture of SDAI remission in those who needed rescue therapy.
The researchers used non-responder imputation for missing data regarding the primary endpoint. In addition, the P value for the primary endpoint was estimated from the Chi-squared test. P values were not adjusted for the secondary endpoints.
According to the researchers, 49.5% of participants in the etanercept-monotherapy group maintained SDAI remission at week 48, compared with 28.7% for the methotrexate arm (P = .004). For those who continued with combination therapy, the week-48 SDAI remission rate was 52.9% (P = .006). Meanwhile, the time to disease worsening in the methotrexate-monotherapy group was shorter compared with both the etanercept-only and combination arms (P < .001).
In patients with disease worsening treated with combination rescue therapy, the cumulative percentage of those who recaptured SDAI remission by study’s end was 71%, 75% and 80% in the methotrexate-only, etanercept-only and combination groups, respectively. The time to SDAI remission recapture after initiating rescue therapy was similar in all three groups. There were no new safety findings.
“SEAM-RA showed that etanercept as monotherapy was significantly more effective than methotrexate as monotherapy to maintain remission,” Curtis said. “Remember that these are RA patients who are starting in sustained, SDAI remission on both, in combo therapy. Similar proportions of patients maintained remission with etanercept monotherapy as continuing with both, so the suggestion and the implication here is that probably if you are doing that well on both treatments, you can continue etanercept and stop methotrexate, and the majority of those people are going to do just as well.”
“Etanercept as monotherapy was associated with a lower proportion of patients with disease-worsening and, for those who did worsen, a longer time to disease worsening, compared with methotrexate as monotherapy,” he added. “But, regardless of treatment arm, almost all patients who needed rescue therapy were able to recapture either remission or at least low disease activity. So, to me as a clinician, the downside or the risk to try this is quite low because the likelihood that you can regain where you were before is quite good. For patients and physicians seeking to reduce treatment burden, these data I think are quite useful to inform decision making.”
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Curtis JR. Abstract 0939. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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