Etanercept Biosimilar Safe and Effectively Treats RA

The results of a recent trial found that patients with moderate-to-severe rheumatoid arthritis (RA) who switched from etanercept (ETN) to biosimilar sandoz etanercept (SDZ ETN) had no changes in outcomes related to safety or efficacy compared to patients who continued treatment with the reference drug. 

The 24-week results of EQUIRAa phase III, double-blind study—reported that patients with moderate-to-severe RA and inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) had comparable outcomes whether they continued ETN therapy or switched to SDZ ETN. 

Herein, we present the 48-week results from the study on the effects of a single switch between ETN and SDZ ETN at week 24 on efficacy, safety, and immunogenicity of etanercept,” the researchers wrote. 

The trial included patients aged ≥ 18 years with an RA diagnosis based on the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 criteria at least six months before baseline. Patients were required to have active disease (disease activity score including 28 joint count [DAS28]-C-reactive protein [CRP] ≥ 3.2); additional inclusion criteria included: 

  • CRP > 5 mg/L or erythrocyte sedimentation rate (ESR) ≥ 28 mm/h 
  • inadequate clinical response to methotrexate (MTX), as well as at least three months of MTX therapy and a stable dose for ≥ 28 days prior to baseline 
  • ≥ 5 mg/week folic acid for ≥ 28 days before baseline. 

Patients with any prior ETN exposure were excluded, as were those with any previous biologic DMARD therapy treatment for RA, including tumor necrosis factor inhibitors, anti-CD20, immune-modulator drugs, other investigational drugs, and/or device(s) within 3 months or 5 half-lives at the time of enrollment. 

The study took place from Nov. 27, 2015, until June 12, 2017, at 83 centers in 16 countries. Patients were randomized 1:1 to self-administer 50 mg SDZ ETN or ETN once a week for 24 weeks. After 24 weeks, the SDZ ETN group who had at least a moderate treatment response per EULAR response criteria continued SDZ ETN treatment, and the ETN patients were switched to SDZ ETN for up to 48 weeks. The primary outcome was 24-week change in DAS28-CRP; secondary outcomes—evaluated at weeks 24 and 48—included change in DAS28-CRP, patients who achieved good and moderate EULAR response per DAS28-ESR, patients who achieved improved ACR20/50/70 response rates, health assessment questionnaire disability index (HAQ-DI) score and patients who achieved HAQ index in normal range, and Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale outcomes. 

A total of 353 patients (SDZ ETN, 181; ETN, 172) completed treatment period one, and 324 (SDZ ETN, 169; ETN, 155) completed treatment period 2. 

Both cohorts had similar DAS28-CRP 48-week change (continued SDZ ETN group, -2.90; switched to SDZ ETN group, -2.78), and a similar proportion of patients achieved good and moderate EULAR responses (good response, 54.4% vs. 51.9%, respectively; moderate response, 41.5% vs. 44.2%, respectively). 

The proportion of patients achieving ACR20, ACR50, and ACR70 response was generally comparable between continued SDZ ETN’ and switched to SDZ ETN groups; ACR50 and ACR70 response rates were numerically higher in the switched to SDZ ETN group at all time-points, but not clinically relevant,” the authors reported. At week 48, ACR20, ACR50, and ACR70 response rates were 89.1%, 63.3%, and 36.7%, respectively, in the continued SDZ ETN group and 82.4%, 65.6%, and 42.0% in the switched to SDZ ETN group. 

After 48 weeks, the mean changes in HAQ-DI score were -0.62 and -0.66 for the continued SDZ ETN and switched SDZ ETN groups, respectively; changes in FACIT-fatigue score were also similar: 11.6 vs. 10.6, respectively. The proportion of patients who achieved normal-range HAQ-DI (≤ 0.5) at week 48 was 34.7% in the continued SDZ ETN group and 39.5% in the switched to SDZ ETN group. 

The study authors concluded, “The 48-week results from the EQUIRA study demonstrate that switch from ETN to the biosimilar SDZ ETN in patients with moderate-to-severe RA did not impact the efficacy, safety, or immunogenicity of a continuous etanercept therapy.