Multicountry Study Provides Insight into Effectiveness, Safety of Etanercept Biosimilars in Rheumatic Disease

Thomas Sheeran, MBChB
Credit: Spire Healthcare

Data from a real-world study of patients with rheumatic disease receiving treatment with SDZ ETN, an etanercept biosimilar, is providing new insight into the real-world persistence, effectiveness, safety, and patient-reported outcomes with etanercept biosimilars among patients in Europe and Canada.

Results of the COMPACT study, which included data from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial-spondyloarthritis (axSpA), provide evidence detailing the efficacy and safety of etanercept biosimilars for these conditions, with treatment persistence rates consistent with previous literature for patients treated with reference or biosimilar etanercept.

“To date, this is the first multi-country real-world study that confirms to have safely and effectively treated a very large set of patients with RA, PsA and axSpA (over 1300) with SDZ ETN under various biosimilar use patterns (groups A–D) in Europe and Canada,” wrote investigators. “The observed high treatment persistence rates and very low discontinuation rates are fully consistent with previously published reports of patients treated with reference or other [etanercept] biosimilars.”

Marketed by Sandoz as Erelzi, SDZ ETN has received approval from the European Commission for the same indications as reference etanercept. The etanercept biosimilar also boasts approvals from the US Food and Drug Administration for treatment of juvenile idiopathic arthritis, RA, PSA, plaque psoriasis and ankylosing spondylitis dating back to 2016. Led by Thomas Sheeran, MBChB, of the University of Wolverhampton, and funded by Novartis, which owned Sandoz before it became a standalone company in October 2023, the COMPACT study was a multicenter, prospective, non-interventional cohort study with drug persistence serving as the primary endpoint of interest.

Conducted in both Europe and Canada, the trial was designed to provide systematic and consistent real-world data from a broad spectrum of patients with rheumatic disease. Per trial protocol, response rates, disease activity information, and patient-reported outcome data was collected from all patients included in the study at week 12, week 24, and around 6-month or 1-year intervals, with a total observation period of 2 years.

Listed inclusion criteria for the study included being at least 18 years of age or older and having a diagnosis of RA, PsA, or axSpA. For the purpose of analysis, patients were categorized into 4 treatment groups based on prior treatment status:

• Group A: Patients in clinical remission or with low disease activity under treatment with reference etanercept or other biosimilar etanercept and switched to SDZ ETN
• Group B: Patients who received non-etanercept targeted therapies and switched to SDZ ETN
• Group C: Biologic-naïve patients considered uncontrolled with conventional therapy and started on SDZ ETN as the first biologic treatment
• Group D: DMARD-naïve patients with a recent diagnosis of RA considered suitable for treatment initiation with a biologic and started on treatment with SDZ ETN

Overall, 1575 patients from 98 centers across 9 countries were enrolled in the study. Of these, 1466 met inclusion criteria. Among this group, 844 had RA, 288 had PsA, and 334 had axSpA as their primary indication. The 1466-patient cohort had a mean age of 54.4 years, 59.8% were female, mean body weight of 76.9 kg, and mean BMI of 27.2 kg/m at baseline. Investigators pointed out there were 572, 171, 713, and 10 patients in groups A, B, C, and D, respectively.

Initial analysis revealed the mean treatment duration with SDZ ETN at time of enrollment among the cohort was 138 (range, 1-841) days, with 22.7% of the cohort going on to discontinue use during the first 12 months. According to investigators, the primary reasons for discontinuation among these patients was adverse events (7.9%) and nonresponse (14.4%). Further analysis suggested groups A, B, and C had discontinuation rates of 15.2%, 25.7%, and 27.8%, respectively, at 12 months. Investigators noted drug persistence rates were difficult to interpret due to the number of patients in the group for group D.

Analysis of effectiveness indicated 51.7% of patients with RA were in remission and 18.5% had low disease activity at month 12. Among those with PsA, 61.9% had achieved remission and 13.3% reported low disease activity at 12 months. Among 154 patients with axSpA, 26.0% had inactive disease and 35.1% had moderate disease activity at baseline. At month 12, among 70 patients with available data, 25.7% had inactive disease and 38.6% had moderate disease activity.

When assessing quality of life, investigators found the overall mean EQ-5D VAS score was 64.9 (SD, 2.2) at baseline and 65.5 (SD, 21.5) and 64.6 (SD, 22.8) at week 12 and month 12, respectively, in patients with RA. In patients with PsA, the corresponding scores at baseline, week 12 and month 12 were 61.5 (SD, 24.1), 64.8 (SD, 21.8) and 69.7 (SD, 18.9). In patients with axSpA, the corresponding scores were 63.6 (SD, 22.8), 66.4 (SD, 21.1), and 67.5 (SD, 22.0), respectively.

“These results support the effectiveness and safety of SDZ ETN treatment in patients with RA, axSpA or PsA in real-life conditions,” investigators added.

References:

1. Schmalzing M, Kellner H, Askari A, et al. Real-World Effectiveness and Safety of SDZ ETN, an Etanercept Biosimilar, in Patients with Rheumatic Diseases: Final Results from Multi-Country COMPACT Study. Adv Ther. Published online November 11, 2023. doi:10.1007/s12325-023-02706-8
2. Deeks ED. GP2015: An Etanercept Biosimilar [published correction appears in BioDrugs. 2018 Aug 1;:]. BioDrugs. 2017;31(6):555-558. doi:10.1007/s40259-017-0246-1
3. FDA approves Erelzi, a biosimilar to enbrel. U.S. Food and Drug Administration. August 30, 2016. Accessed November 28, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-erelzi-biosimilar-enbrel.
4. Novartis confirms Sandoz spin-off for October 4, 2023. Novartis. September 25, 2023. Accessed November 28, 2023. https://www.novartis.com/news/media-releases/novartis-confirms-sandoz-spin-october-4-2023.