Real-world effectiveness and persistence of reference etanercept versus biosimilar etanercept GP2015 among rheumatoid arthritis patients: A cohort study

Abstract

Although several randomized clinical trials have confirmed that there is no difference in efficacy between etanercept and its biosimilar versions in the treatment of rheumatoid arthritis (RA), limited real-world evidence is available. We conducted a cohort study to compare the effectiveness and treatment persistence between the reference etanercept (ETN) and the biosimilar GP2015 in RA patients in a real-life setting. Adults with a diagnosis of RA who initiated treatment with ETN or GP2015, between January 2007 and December 2019, were included. The follow-up period was 52 weeks. The primary outcome was the mean of change in the DAS28-CRP values and the adjusted mean difference from baseline to 52 weeks between ETN and GP2015. Other effectiveness endpoints assessed were the rate of patients who achieved remission or low disease activity (LDA) at week 52, who showed a reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 and rate of good responder patients (those meeting both effectiveness measures) at week 52. Treatment effectiveness over time (baseline, 26 and 52 weeks) was compared between the ETN and GP2015 groups using mixed effects models. Treatment persistence (probability of maintaining the same treatment over time) was also evaluated and shown using Kaplan-Meier survival curves. A total of 115 RA patients were included (ETN, n = 90; GP2015, n = 25). No differences were observed in the primary outcome: DAS28-CRP score decreased from baseline to week 52 [5.1 to 2.7 (mean of change -2.37) in ETN group and 5.0 to 2.2 (mean of change -2.84) in GP2015 group, p-value = 0.372] and the adjusted mean difference was -0.37 (-1.03 to 0.29). No differences were also observed in the other effectiveness endpoints assessed among patients treated with ETN or GP2015: rate of patients who achieved remission (54.1% vs. 66.7%, p-value = 0.303) and LDA (71.6% vs. 80.9%, p-value = 0.391) at week 52, reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 (75.6% vs. 80.9%, p-value = 0.613) and rate of good responder patients (58.1% vs. 76.1%, p-value = 0.202). Drug survival was 82% and 80% for ETN and GP2015, respectively (log-rank p-value = 0.804). Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting.

Keywords: GP2015; biosimilar agents; drug survival real-life data; effectivenes; etanercept (enbrel); rheumatoid anhritis.

FIGURE 1

The study flow chart in line with the STROBE: 186 patients were initially assessed for eligibility, of which 71 were excluded. Finally, 115 patients were analyzed, 90 in the group ETN-treated patients and 25 in the group GP2015-treated patients. All patients completed the follow up. STROBE: (Strengthening the Reporting of Observational Studies in Epidemiology).

FIGURE 2

Proportion of patients achieving remission defined as DAS28-CRP ≤2.6 and low-disease activity score (LDAS) defined as DASR28-CRP ≤3.2. The rate of patients who achieved remission at week 52 were 40 (54.6%) and 14 (66.7%), p-value = 0.303, in the ETN and GP2015 group, respectively. Fifty-three (71.6%) patients in the ETN group and 17 (80.9%) in the GP2015 group (p value = 0.391) achieved LDAS.

FIGURE 3

Rate of good responder patients: who achieved low disease activity (DAS28-CRP ≤ 3.2) at week 52 and show a significant change of 1.2 in DAS28-CRP from baseline to 52 weeks. It was reached in 43 (58.1%) and 16 (76.1%) patients in the ETN and GP2015 group respectively, p-value = 0.202.

FIGURE 4

Mean change from baseline over 52 weeks in DAS28-CRP and DAS28-ESR scores of ETN and GP2015 groups. DAS28-CRP disease activity score 28 using c-reactive protein, DAS28-ESR disease activity score 28 using erythrocyte sedimentation rate, ETN etanercept originator (Enbrel^®), GP2015 etanercept biosimilar (Erelzi^®). DAS28-CRP (p-value = 0.263). DAS28-ESR (p-value = 0.293)

FIGURE 5

Overall treatment persistence with ETN and GP2015 in RA patients shown as the fraction (between 1 and 0) of patients remaining on therapy during 52 weeks after therapy initiation (long-rank p = 0.804).