Systematic Review Underscores the Safety and Efficacy of SB4 in Both Switched and New Patients

Samsung Bioepis’ etanercept biosimilar, SB4, has been available in multiple markets since it was authorized by the European Commission in 2016, and this week, a new systematic review reported on real-world evidence on the use of the biosimilar in treating inflammatory diseases.

Samsung Bioepis’ etanercept biosimilar, SB4 (approved under the name Eticovo in the United States and under the names Brenzys and Benepali in other regulatory territories) has been available in multiple markets since it was authorized by the European Commission in 2016, and this week, a new systematic review reported on real-world evidence on the use of the biosimilar in treating inflammatory diseases.

The review’s authors identified 6 journal articles, 2 journal letters, and 23 congress abstracts that met their inclusion criteria. These studies included a total of 13,552 patients across all indications of the product. Of this number, 2499 patients were naïve to etanercept, while the remaining 11,053 patients were switched from the reference product to the biosimilars (most switches were nonmedical).

One study showed that pre- and postswitch changes over 3 months in terms of a range of disease activity measures were not clinically different. Another study showed no statistically significant difference between the 6-month change in disease activity in a historic cohort of patients treated with the reference versus those who switched. Still another study, exclusively in patients with psoriasis and psoriatic arthritis, showed no difference in rates of clinical remission before and after a switch. Additionally, most congress reports on SB4 showed no clinically meaningful differences between pre- and postswitch disease activity or changes over time between those who switched and historic cohorts. The BSRBR-RA registry found that the effectiveness of the biosimilar in new patients was not different from the effectiveness of the reference.

Patients’ risk of serious adverse events (AEs) was similar between those who initiated the biosimilar versus those who initiated the reference, and no significant differences were observed in the number of AEs among patients who switched and those who were new starts on the biosimilar. No new safety signals were identified.

In terms of patients’ willingness to switch to the biosimilar, the investigators found that mandatory switches did not necessarily result in higher rates of switching than nonmandatory ones; in the nonmandatory BIO-SPAN study, 99% of patients agreed to switch, versus 79% of patients in the DANBIO registry. (Among the reasons for some patients not switching in the DANBIO experience was the commercial unavailability of the appropriate dosage strength of the biosimilar.)

Patient support programs were associated with higher switch rates over 12 months (95%) than less intensive patient education and support (75%). Patient characteristics of those who refused to switch were similar to those of patients who accepted switches, with the exception of holding a negative view of generic drugs and a statistical trend toward older age and longer disease duration.

In the BIO-SPAN study, 10% of patients who switched discontinued, versus 8% in a cohort of reference product—treated patients. Discontinuation of the biosimilar was linked with lower self-reported efficacy and shorter duration of reference etanercept treatment. The DANBIO registry also showed a lower retention rate over 12 months for those who switched, and retention rates were lower in patients not in remission at the time of the switch. In the DERMBIO registry, discontinuation did not differ significantly between biosimilar-treated and reference-treated patients. Retention rates over 6 months post switch that were reported in congress abstracts ranged from 82% to 91%.

Across studies, the rate of patients switching back to the refence varied from 4.6% to 26.4%. Evidence from the DANBIO registry suggests that subjective reasons may be drivers of switching back to the reference etanercept; changes in disease activity among those who switched back were mainly in Patient Global Scores, with no or few changes in C-reactive protein or swollen joint count. Reasons for switching back that were reported in congress abstracts showed AEs to be the most frequent reason for changing treatment.

“Real-world data opens the window to what is actually happening in clinical practice,” wrote the authors, adding that although their review was limited by the quantity of data available for each study and by other factors, the evidence presented in the review “provides additional reassurance that the biosimilar approval pathway is robust and that SB4 is as effective and safe as [the reference] in both switched and naïve patients.”


Ebbers HC, Pieper B, Issa A, Addison J, Freudensprung U, Rezk MF. Real-world evidence on etanercept biosimilar SB4 in etanercept-naïve or switching patients: a systematic review [published online August 5, 2019]. Rheumatol Ther. doi: 10.1007/s40744-019-00169-4.