Open-Label, Non-Mandatory Transitioning From Originator Etanercept to Biosimilar SB4: Six-Month Results From a Controlled Cohort Study.

To evaluate the effects of non-mandatory transitioning from the originator biologic drug etanercept (ETN) to its biosimilar, SB4, on drug survival and effectiveness in a controlled cohort study of patients with an inflammatory rheumatic disease. In 2016, 642 patients were asked to transition their treatment from originator ETN to biosimilar SB4 by a structured communication strategy with opt-out option. Patients who consented to switch to SB4 were considered eligible for inclusion in the transition cohort, while patients being treated with originator ETN in 2014 were recruited as the historical cohort. Drug survival was compared between the 2 cohorts using Cox regression analyses, which were adjusted for age, sex, diagnosis, ETN treatment duration, ETN dose interval, conventional synthetic disease-modifying antirheumatic drug usage, and C-reactive protein (CRP) level, with a robust variance estimator applied to account for repeated subjects (i.e., patients who were included in both the transition cohort and the historical cohort). Adjusted differences in the 6-month change in CRP level, Disease Activity Score in 28 joints using CRP level (DAS28-CRP), and Bath Ankylosing Spondylitis Disease Activity Index were also assessed. Of the 642 ETN-treated patients, 635 (99%) agreed to transition from originator ETN to biosimilar SB4, of whom 625 patients (433 with rheumatoid arthritis, 128 with psoriatic arthritis, and 64 with ankylosing spondylitis) were included in the transition cohort, and 600 ETN-treated patients from 2014 were included in the historical cohort. The crude treatment persistence rate for biosimilar SB4 over 6 months was 90% (95% confidence interval [95% CI] 88-93%), compared to a 6-month treatment persistence rate of 92% (95% CI 90-94%) for originator ETN. Patients in the transition cohort, compared to the historical cohort, had a statistically significantly higher relative risk of treatment discontinuation (adjusted hazard ratio 1.57, 95% CI 1.05-2.36) and showed smaller decreases in the CRP level (adjusted difference 1.8, 95% CI 0.3-3.2) and DAS28-CRP (adjusted difference 0.15, 95% CI 0.05-0.25) over 6 months. Non-mandatory transitioning from originator ETN to biosimilar SB4 using a specifically designed communication strategy resulted in a slightly lower 6-month treatment persistence rate and smaller decreases in disease activity in the transition cohort compared to the historical cohort, but these differences were not considered clinically relevant.

Tweehuysen L ，Huiskes VJB ，van den Bemt BJF ，Vriezekolk JE ，Teerenstra S ，van den Hoogen FHJ ，van den Ende CH ，den Broeder AA ... -  《-》

Post-switch Effectiveness of Etanercept Biosimilar Versus Continued Etanercept in Rheumatoid Arthritis Patients with Stable Disease: A Prospective Multinational Observational Study.

To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission). The study recruited adult patients (18 years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6 months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3 months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12 months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month 6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded. Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month 12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95% CI 15.0-32.2]) and SB4 group (17.6% [95% CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month 6 (ETN: 7.9% [95% CI 3.5-15.0]; SB4: 7.8% [95% CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%). SB4 demonstrated comparable effectiveness to ETN over 12 months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

Pope J ，Hall S ，Bombardier C ，Haraoui B ，Jones G ，Naik L ，Etzel CJ ，Ramey DR ，Infante R ，Miguelez M ，Falcao S ，Sahakian S ，Wu D ... -  《-》

To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry.

Real-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised. Observational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted). 1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months' preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers' clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective. Seventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Glintborg B ，Loft AG ，Omerovic E ，Hendricks O ，Linauskas A ，Espesen J ，Danebod K ，Jensen DV ，Nordin H ，Dalgaard EB ，Chrysidis S ，Kristensen S ，Raun JL ，Lindegaard H ，Manilo N ，Jakobsen SH ，Hansen IMJ ，Dalsgaard Pedersen D ，Sørensen IJ ，Andersen LS ，Grydehøj J ，Mehnert F ，Krogh NS ，Hetland ML ... -  《-》

Comparative Effectiveness and Persistence of SB4 and Reference Etanercept in Patients With Psoriatic Arthritis in Norway.

We aim to compare drug effectiveness and persistence between the reference etanercept (ETN) and ETN biosimilar SB4 in patients with psoriatic arthritis (PsA) naive to ETN and to investigate drug effectiveness and persistence in those undergoing a mandatory nonmedical switch from ETN to SB4. We used a retrospective comparative database study including 1,138 patients with PsA treated with ETN or SB4 (years 1999-2021) in Norway. Disease activity score in 28 joints (DAS28) and drug persistence were compared between unmatched ETN (n = 644) and SB4 (n = 252) cohorts and in matched analyses (n = 144, both cohorts) at baseline using a propensity score (PS) to adjust for confounders. Drug persistence was analyzed with the Kaplan-Meier method. In unmatched analyses, difference in change from baseline between ETN (n = 140) and SB4 (n = 132) for DAS28 at one year was mean 0.67 (95% confidence interval [CI] 0.38-0.96) in favor of ETN. In PS-matched analyses, the difference in change from baseline between ETN (n = 54) and SB4 (n = 54) was mean 0.09 (95% CI -0.33 to 0.50), and the mean difference assessed with an analysis of covariance model was 0.01 (95% CI -0.38 to 0.40), both within predefined equivalence margin (±0.6). Drug persistence at one year was mean 0.75 (95% CI 0.71-0.78) for ETN, mean 0.58 (95% CI 0.51-0.63) for SB4, hazard ratio (HR) 2.45 (95% CI 2.02-2.97) in unmatched analysis, and mean 0.55 (95% CI 0.46-0.63) for ETN, mean 0.60 (95% CI 0.51-0.67) for SB4, HR 1.29 (95%CI 0.94-1.76) in PS-matched cohorts. At one year, outcomes for PsA disease activity and drug persistence were comparable for patients treated with either ETN or SB4. In patients undergoing a mandatory nonmedical switch from ETN to SB4, drug effectiveness was maintained during a two-year period.

Łosińska K ，Pripp AH ，Bakland G ，Fevang BS ，Brekke LK ，Wierød A ，Korkosz M ，Haugeberg G ... -  《-》

Comparative effectiveness of etanercept originator and biosimilar for treating rheumatoid arthritis: implications for cost-savings.

This study aimed to assess the comparative effectiveness of the etanercept (ETN) originator (Enbrel) and ETN biosimilar SB4 (Brenzys) as first-line treatment in patients with rheumatoid arthritis (RA), while also exploring the potential cost-savings associated with this approach in Australia. Clinical data were obtained from the Optimising Patient outcomes in rheumatoLogy Australian real-world data set. Adult patients with RA who had initiated treatment with the ETN originator or biosimilar as their first-recorded biologic or targeted synthetic disease-modifying antirheumatic drug between 1 April 2017 and 31 December 2020 were included. Treatment persistence was analysed using survival analysis. Cost-savings were estimated based on data reported by the Australian National Prescribing Service MedicineWise. Propensity score matching followed by inverse probability of treatment weighting selected patients taking originator (n = 209) or biosimilar (n = 141) with similar baseline characteristics and eliminated small differences in baseline disease activity. The median time for 50% of the patients to stop treatment was 19.4 months (95% confidence interval [CI], 14.7-36.4 months) for the originator and 22.4 months (95% CI, 15.0-33.1 months) for the biosimilar (P = 0.95). As a result of pricing policies established by the Australian Government, introduction of the ETN biosimilar would have resulted in a cost-savings of over AU$9.5 million for 1 year of treatment for the patients reported in this study. Treatment persistence using either ETN originator or biosimilar was similar. The cost of all brands of ETN markedly reduced upon listing of the ETN biosimilar, resulting in significant savings for the Australian Government.

Deakin CT ，Littlejohn GO ，Griffiths H ，Ciciriello S ，O'Sullivan C ，Smith T ，Youssef P ，Bird P ，OPAL consortium ... -  《-》