Newly Presented Data on SB4 Show Successful Switches, Safe Use, and No Evidence of Nocebo

While US patients continue to wait for a biosimilar etanercept to become commercially available, real-world data continue to amass for Samsung Bioepis’ biosimilar, SB4, in European clinical practice. The biosimilar, sold as Benepali in the European context, was the subject of several studies presented this week at the American College of Rheumatology’s 2019 meeting, held in Atlanta, Georgia.

Similar retention observed in patients who did, did not switch to SB4

A German study compared treatment survival between patients with rheumatoid arthritis (RA) who switched from reference etanercept to SB4 and those who continued to receive the originator drug after biosimilars became available in 2016.¹ The study used data from patients treated with reference etanercept for at least 6 months who were part of the prospective, longitudinal RABBIT cohort until November 2018.

In total, 102 switched patients could be matched to 598 nonswitched patients. After 1 year, 23% of those who switched and 17% of those who did not switch had stopped etanercept. Among the biosimilar group, the most frequent reason for discontinuation was adverse events (AEs) (56%), and among the reference group, loss of response was the most frequently cited (66%). Nine patients switched back to the reference drug.

According to the authors, Kaplan-Meier curves showed similar retention rates over 12 months.

DANBIO data give reassuring insight into hepatobiliary events with biosimilar use

Additionally, new data from real-world clinical practice in Denmark may provide reassurance about the safety of SB4; in a phase 3 clinical trial, the biosimilar had a slightly higher occurrence of hepatobiliary AEs versus the originator, which may have been linked with comorbidities and concomitant medication.

Using data from the nationwide DANBIO registry, which collects clinical information among all Danish patients with inflammatory diseases, researchers conducted an observational study of a cohort of 5738 patients who initiated treatment with reference etanercept prior to biosimilar availability in 2016 (n = 2748) and patients who were treated with the biosimilar (n = 2990; 52% were switched from the reference) once it became available.²

In the first 6 months of treatment, there were 50 hepatobiliary AEs, 23 of which resulted in hospitalization. Among the 50 patients experiencing these AEs, 14 were receiving concomitant methotrexate. The AEs included gallbladder stones, elevated transaminases, liver cirrhosis, and pancreatitis.

While there were no significant differences in hepatobiliary AEs between groups, there was a tendency toward a lower incidence of hepatobiliary events among patients who had switched to the biosimilar, said the investigators.

Nocebo? No evidence, say researchers

Finally, another study from Germany, conducted at the Ruhr University Bochum in Herne, Germany, contributed to the growing conversation about the role of the nocebo effect—whereby a patient experiences a worsening of symptoms or poor outcomes because of negative beliefs about a given therapy—in the success or failure of nonmedical switches.³

Some have hypothesized that subjective disease worsening or discontinuation after a switch may be linked with this effect and that better patient education may have a role in addressing the phenomenon, but the study found that switching to SB4 was not linked changes in disease activity or function for patients at 12 weeks, regardless of how patients were informed about the switch.

The study examined outcomes for 84 patients with RA, axial spondyloarthritis, and psoriatic arthritis who were switched to the biosimilar; in the center, whether to inform patients about the switch was left to the treating physician. In total, 24 patients were given information about the switch, and the others were not informed.

Disease activity and function were unchanged at week 12, and whether patients had been informed about the switch did not influence outcomes or the incidence of AEs. Retention at week 12 was 96.4%, and at week 24, it was 87.6%. There were 18 AEs in 10 patients. For 3 patients who had 5 AEs in the first 12 weeks, originator etanercept was reinitiated successfully.

According to the authors, in this study in routine clinical practice, there was no evidence to support a nocebo effect related to a nonmedical switch.

References

1. Baganz L, Strangfeld A, Herzer P, Krause A, Tony HP, Zink A. Comparing real-world retention rates in a matched cohort of rheumatoid arthritis patients who either remained on the etanercept originator or switched to a biosimilar. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, GA. Abstract 540.

2. Glintborg B, Georgiadis S, Norgaard M, et al. Hepatobiliary events in >5000 patients with inflammatory arthritis treated with biosimilar or originator etanercept in routine care, results from the Danish nationwide DANBIO registry. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, GA. Abstract 2406.

3. Kiltz U, Tsiami S, Baraliakos X, Braun J. Nonmedical switching from reference to biosimilar etanercept—no evidence for nocebo effect—a retrospective analysis of real-life data. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, GA. Abstract 1116.