Clinical Edge

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Value of Very Early Etanercept Plus Methotrexate Not Confirmed in Real-World RA Trial

Key clinical point: A randomized study representing real-world clinical practice did not confirm that patients with very early rheumatoid arthritis (RA) obtain an outsized benefit from first-line etanercept plus methotrexate compared with a strategy of methotrexate and delayed etanercept.

Major finding: A 14% difference in remission rate was not on par with a 30% effect size seen in an exploratory analysis of the very early RA subset in a previous early RA trial.

Study details: Results from VEDERA, a phase 4, open-label, single-center, randomized trial of 120 adult patients with new-onset early RA with symptom duration of less than 12 months.

Disclosures: The study was funded through an investigator-sponsored research grant provided by Pfizer. Three authors disclosed financial relationships with multiple pharmaceutical companies that market drugs for RA, including Pfizer.


"One of the benefits of a treat-to-target strategy as well as identifying RA patients with early active disease is that early treatment is presumed to be beneficial in preventing long-term joint damage. A previous post hoc analysis of the COMET study suggested improved disease control in treatment of very early RA (<4 months duration) compared to patients with early RA (between 4 months and 2 years duration), with a higher proportion of patients achieving low disease activity or remission after treatment with a combination of etanercept and methotrexate compared to methotrexate alone. The current study is a pragmatic randomized study similarly comparing etanercept and methotrexate combination therapy with methotrexate alone. A smaller effect size was seen though the proportion of patients reaching remission was still higher in the combinations etanercept-methotrexate group. Interestingly, however, escalation of patients receiving methotrexate monotherapy to combination therapy with etanercept did not improve the rate of remission. Unfortunately the causes of these discrepancies are not certain, but perhaps continued research on the subsets of patients who benefit most would help."

Arundathi Jayatilleke, MD


Emery P et al. Ann Rheum Dis. 2020 Jan 29. doi: 10.1136/annrheumdis-2019-216539.