Etanercept, Adalimumab, JAK Inhibitors Similarly Benefit Rheumatoid Arthritis at 1 Year

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A comparison of monotherapy biologic or targeted synthetic DMARDs initiated in naive patients show each are beneficial for rheumatoid arthritis.

Etanercept, adalimumab and Janus kinase (JAK) inhibitors did not significantly vary in neither rheumatoid arthritis (RA) disease progression nor patient-reported outcomes after 1 year when initiated as a monotherapy, according to new data.

New comparative research presented at the Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting in Destin, FL this week showed an extent of consistency between available biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for the monotherapy treatment of RA. The findings support rationale for tailored DMARD regimen initiation and alteration dependent on the patient.

Led by Dimitrios Pappas, MD, MPH, assistant professor of medicine at Columbia University College of Physicians and Surgeons, the US-based team of investigators sought to contribute to insights around available first-line use of etanercept, adalimumab and JAK inhibitors in RA through a real-world analysis. The agents are representative of the modern DMARD drug class, and have been historically used as monotherapy for the treatment of rheumatic disease.

“However, little is known about the comparative effectiveness of these therapies when used as monotherapy,” Pappas and colleagues noted.

The Amgen-sponsored, prospective, observational analysis used data from the multicenter, disease-based CorEvitas RA registry to identify patients who initiated first-line monotherapy with any of the 3 agents. Eligible patients were naïve to biologic or targeted synthetic DMARDs.

Investigators reported descriptive analysis of baseline information, persistency on therapy, drug-switching patterns, and effectiveness of treatment-based outcomes, evaluated at 6 and 12 months. Their assessment included 550 patients initiating either etanercept (n = 218), adalimumab (n = 212) or JAK inhibitors (n = 120). Mean Baseline Clinical Disease Activity (CDAI) scores were 18.7, 16.7 and 19.3, respectively. Mean patient pain scores were 49.2, 52.7, and 41.9 out of 100 at baseline, respectively.

Patients receiving JAK inhibitors were, on average, older (61.8 years) more likely be female (78.3%), and diagnosed with RA longer (8.2 years) than the etanercept and adalimumab arms.

Approximately two-thirds of each patient arm remained on their initiated DMARD by 6 months (etanercept, 64.5%; adalimumab, 65.4%; JAK inhibitors, 62.4%). Those rates dropped to 50.7%, 57.3% and 48.1%, respectively, at 12 months.

Investigators observed that 9.6% of etanercept patients switched to another biologic or targeted synthetic DMARD at 6 months; the rate increased to 22.8% at 12 months. Among the adalimumab arm, switch rates were 12.0% at 6 months and 25.2% at 12 months. Among the JAK inhibitor arm, rates were 15.4% and 20.8%, respectively.

At 12 months, 136 patients remained on etanercept; 143 remained on adalimumab and 77 remained on JAK inhibitors. Mean patient improvement in CDAI ranged from 5.6 (95% CI, 3.3 – 7.9) among the etanercept group to 3.8 (95% CI, 0.6 – 7.0) among the JAK inhibitor group at 12 months. Patient pain scores additionally improved by 8.0 points (95% CI, 2.3 – 13.7) in the etanercept group; 8.4 (95% CI, 3.5 – 13.4) in the adalimumab group; and 1.5 (95% CI, -5.3 to 8.3) in the JAK inhibitor group.

Odds ratios (ORs) for achieving LDA relative to etanercept were 0.88 (95% CI, 0.49 – 1.59) for patients who initiated adalimumab and 1.04 (95% CI, 0.50 – 2.16) for patients who initiated JAK inhibitors, at 6 months. Pappas and colleagues noted that 47 (44.8%) patients on etanercept achieved low disease activity (LDA), versus 32 (32.0%) adalimumab patients and 19 (34.5%) JAK inhibitor patients, at 12 months.

Indeed, the investigators concluded patients with RA who initiate their first biologic or targeted synthetic DMARD as a monotherapy did not differ significantly in neither 6-month or 12-month efficacy.

“The findings of non-significant differences between first-line etanercept, adalimumab and JAK inhibitor monotherapy initiators suggest that multiple approaches to the initial therapy are appropriate,” they wrote.


  1. Pappas DA, O’Brien J, Kelleman M, Guo L, et al. Outcomes in Patients With Rheumatoid Arthritis Initiating Monotherapy With Etanercept, Adalimumab, or Janus Kinase Inhibitors. Paper presented at: Clinical Congress of Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.