Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study

Abstract

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Keywords: SB4; anti-TNF; biosimilar; drug survival; inflammatory arthritis.

Figure 1

Kaplan–Meier curve showing retention rate in RA, PsA and AS patients over 3 years treated with SB4 after ETA failure. (A) Cumulative retention probability in RA, PsA and AS patients; (B) retention rate in all patients with and without comorbidity. AS = ankylosing spondylitis; ETA = etanercept; PsA = psoriatic arthritis; RA = rheumatoid arthritis.

Figure 2

Box and whisker plots illustrating changes in disease activity for the different pathologies (RA, PsA and AS) over the follow up period. (A) DAS 28 was measured in RA patients, (B) DAPSA in PsA patients and (C) BASDAI in AS patients, respectively, at baseline and after 3 years of treatment with SB4. Data presented as median, 25th/75th percentiles and maximum/minimum recorded values. Orange open dots represent standard outliers (fall between 1.5 × IQR and 3.0 × IQR outside of the IQR,) whereas red full dots represent extreme outliers (fall greater than 3.0 × IQR outside the IQR).

Figure 3

Forest plots showing predictive variables of maintaining the response after switch from ETA to SB4. (A), Model#1 including all patients, (B), Model#2 stratified for RA patients and (C), Model#3 in patients who were seronegative (i.e., PsA and AS patients). Data presented as hazard ratio (HR) and 95% confidence intervals (CI). CCI = Charlson Comorbidity Index; HAQ = Health Assessment Questionnaire; PsA = psoriatic arthritis; RA = rheumatoid arthritis.

Figure 4

Flow diagram showing the number of patients discontinuing SB4 treatment after receiving ETA.