Originator Etanercept Research Articles

Drug utilization and medication adherence for the treatment of psoriatic arthritis: an Italian study.

This study aims to evaluate the persistence, treatment adherence and drug cost associated with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the management of psoriatic arthritis (PsA) in Italy, with a focus on biosimilar drugs. This was a retrospective observational study involving eight hospital pharmacies, between January 2017 and December 2020, on naïve patients with at least one b/tsDMARD dispensation indicated for PsA. Patients were followed up for 12 months and persistence and adherence were evaluated by proportion of days covered (PDC). The originator and biosimilar for adalimumab and etanercept were compared. Furthermore, the real annual cost per patient based on adherence to therapy was calculated. Patients initiating b/tsDMARDs for PsA had a mean persistence of 263 days and 48.6% remained persistent for 1 year. Adherent patients (PDC ≥ 0.8) were 47.6% for the overall population. Similar persistence and adherence were observed between patients treated with the adalimumab originator and its biosimilar, while patients treated with the etanercept originator showed lower persistence and adherence compared to those treated with its biosimilar (mean persistence: 222 vs. 267 days, patient persistent at 1 year: 29.4% vs. 51.5%, mean PDC: 0.53 vs. 0.70, adherent patients: 23.5% vs. 51.5%). The average annual drug cost ranged from €8,724 (etanercept) to €14,783 (ustekinumab), with an annual saving of more than €2,500 by using biosimilars. Poor adherence to medications contributes to suboptimal clinical outcomes. The comparison between biosimilar and originator offers further evidence in support of the biosimilar to optimizing resources in healthcare.

Efficacy, safety and immunogenicity of the biosimilar etanercept compared to the reference formulation original etanercept in patients with rheumatoid arthritis: An open-label, randomized, comparative, multicenter study.

The objective of this phase III clinical randomized trial was to establish the therapeutic equivalence of biosimilar etanercept (bio-etanercept) with original etanercept (O-etanercept) for patients diagnosed with rheumatoid arthritis. The study (NCT04079374) enrolled patients with moderate to high disease activity rheumatoid arthritis. Enrolled patients were randomized 1:1 into 2 treatment groups, 1 receiving bio-etanercept (study drug) and the other receiving O-etanercept (comparator) at a dose of 25mg twice weekly, for 24 weeks. The primary efficacy endpoint was the number of patients with an ACR20 response after 24 weeks of treatment. Safety (adverse reaction/adverse event) and immunogenicity of both drugs were evaluated. Among 156 patients (79 in the bio-etanercept group and 77 in the O-etanercept group) who completed 24-week treatment and 4-week follow-up, 82.3% (65 patients) and 90.9% (70 patients) achieved an ACR20 response in the bio-etanercept and O-etanercept groups, respectively. There was no significant difference between the 2 groups (P = .16). No significant differences in the occurrence of adverse reactions/adverse events were found between the 2 groups regardless of severity (P = .63 for mild, P = .43 for moderate and P > .99 for severe). The development of antibodies in the bio-etanercept group was observed in 4 (5.1%; visit 6), 4 (5.0%; visit 9), and 3 (3.8%; visit 11) patients, and in 5 (6.4%), 5 (6.5%), and 3 (4.1%) patients in the O-etanercept group. The differences between the 2 groups were not significant (P > .99). This study showed that bio-etanercept was equivalent to the reference formulation.

Efficacy of switching from originator etanercept to biosimilar YLB113 in real-world patients with rheumatoid arthritis: A retrospective 12 months follow-up study.

Purpose: To investigate the disease activity in real-world patients with rheumatoid arthritis (RA) who switched from originator etanercept (ETN) to biosimilar YLB113. Methods: Forty one RA patients who switched from ETN to YLB113 were divided into 2 groups based on the Disease Activity Score based on the 28-joint count (DAS28) 12 months after switching (R group: DAS28 < 2.6, N group: DAS28 ≥ 2.6), and the baseline characteristics were statistically examined. A receiver operating characteristics (ROC) analysis was performed to estimate the cut-off value of DAS28 at baseline to achieve remission 12 months after switching. Results: There was no significant difference in the DAS28 at baseline and 12 months after switching (p = .83). Sixteen out of the 20 patients in remission at baseline achieved remission after switching. A univariate analysis revealed the rheumatoid factor (p = .04) and DAS28 (p < .001) at baseline were significantly lower in the R group than in the N group. Furthermore, logistic regression analysis revealed DAS28 was an independent factor (p = .004) for achieving remission 12 months after switching. An ROC curve analysis showed the optimal cut-off value for DAS28 at baseline to achieve remission at 12 months after switching was 2.5. Conclusions: RA patients who achieved remission using originator ETN, were able to maintain remission even if they switched to YLB113.

Evaluation of the nocebo effect after switching from etanercept or adalimumab originator to a biosimilar: a retrospective study of patients with inflammatory rheumatism.

Despite significant savings with biosimilars, their negative perception can lead to the occurrence of a nocebo effect (NE), therefore we aimed to quantify the NE in inflammatory rheumatism after switching from adalimumab or etanercept originators to biosimilars. This retrospective study was conducted in 4 hospitals in Normandy, France between January 2018 and July 2022. The study included patients with rheumatoid arthritis or spondyloarthritis in remission under adalimumab or etanercept originators before switching to biosimilars. The occurrence of a NE was considered in patients who did not maintain biosimilars at 12 months and who presented a subjective adverse event (AE). A comparative analysis of the quantitative data collected before and after switching was performed. The AE that led to biosimilar discontinuation was identified. Additional analyses were performed to identify potential risk factors for the occurrence of a NE. Among 183 patients included,13.1% presented a NE. Objective AEs were observed, including rheumatism reactivation (15.3%), intolerance (8.2%), infection (1.6%) and allergic reactions (0.5%). Morning stiffness duration was significantly different before and after the switch in the spondyloarthritis group (p=0.01). No risk factors were associated with the occurrence of a NE within the limits of the studied parameters. The occurrence of a NE after switching to a biosimilar remains acceptable. It appears less frequent when the switch is supervised by the practitioner rather than being systematic (up to 33% in some countries). A shared medical decision seems to be essential in a subset of patients, which remains to be defined.

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.

Outcomes following switching from etanercept originator to etanercept biosimilar in 1024 patients with RA: a matched-analysis of the BSRBR-RA.

Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator. Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched vs remaining on originator. Change in DAS28 after 6months and 12months was compared between cohorts. Multiple imputation was used. A total of 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on the originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment vs those who remained on the originator; hazard ratio 1.06 (95%CI 0.89-1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to the originator within the first year. After 6months and 12months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6units) compared with those who remained on the originator. This is the largest matched comparative effectiveness analysis showing patients switching from etanercept originator to biosimilar appearing to do just as well with regard to disease activity and drug persistence compared with those who remained on the originator. These data will be reassuring to clinicians and patients regarding non-medical switching.

P66 Uptake of biosimilars for psoriasis: a drug utilization study from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Tumour necrosis factor-α inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expirations of TNFi originators, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. This observational cohort study aimed to describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Republic of Ireland (RoI). This study utilized data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a national pharmacovigilance register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England, along with Wales, Scotland, Northern Ireland and the RoI. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originator infliximab, etanercept and adalimumab at the time originator patents expired entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model. In total, 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab) were included in the originator-user cohort. For infliximab, etanercept and adalimumab, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years, respectively. Across geographical regions, 3-year switching rates varied from 0% (North East England, London, Scotland, Northern Ireland, RoI) to 43.7% (East Midlands) for infliximab; from 0% (RoI) to 40.4% (South West England) for etanercept; and from 12.5% (London) to 84.3% (North East England) for adalimumab. After switching to biosimilars, 2.8% of switchers cross-switched to other biosimilars, 1.1% switched back to the originator and 17.1% discontinued or switched to other biologic medicines. In total, 528 patients were included in the adalimumab-naïve cohort, of whom 67.8% started on biosimilars. Amgevita® and Imraldi® were the most commonly used biosimilars among adalimumab biosimilar switchers (56.8% and 39.1%, respectively) and starters (53.6% and 34.4%, respectively). Originator-to-biosimilar switching and biosimilar initiation were more common in patients who were male or had lower a Psoriasis Area and Severity Index at cohort entry. The uptake of biosimilars increased over time and varied considerably across the UK and RoI; adalimumab had the highest biosimilar uptake rate compared with other TNFi.

Biosimilar competition in European markets of TNF-alpha inhibitors: a comparative analysis of pricing, market share and utilization trends.

Background: Factors like the number of biosimilar competitors and competitive pricing strategies from originator companies may influence price competition and biosimilar uptake. Objective: The aim of this study was to analyze multiple facets of biosimilar competition of TNF-alpha inhibitors in Europe by exploring the existence of a biosimilar first-mover advantage, pricing strategies of originator companies, and the evolution in patient access. Methods: Sales and volume data on biosimilar and originator infliximab, etanercept, and adalimumab between 2008 and 2020 were provided by IQVIA. Countries included 24 European Union Member States, Norway, Switzerland, United Kingdom, Serbia, and Bosnia and Herzegovina. Sales value was expressed as ex-manufacturer price per defined daily dose (DDD), and volume data were transformed into the number of DDDs per 1,000 inhabitants per day. Descriptive analyses were conducted based on the evolution in price per DDD, trends in biosimilar and originator market shares and utilization trends. Results: Market entry of the first biosimilars of infliximab and adalimumab resulted in a decrease of the volume-weighted average price (VWAP) per DDD by 13.6% and 0.9% on average, whilst the second biosimilars resulted in a decrease by 26.4% and 27.3%, respectively. The first and second etanercept biosimilars generated a similar decrease in the VWAP per DDD by 9.3% and 9.1% on average, respectively. Average market share captured by the first biosimilars was at least twice as large as the second biosimilars for all molecules. In addition, sharp reductions in price per DDD of Humira® in most countries indicated a pricing strategy resulting in low uptake of adalimumab biosimilars. Lastly, utilization of infliximab, etanercept, and adalimumab following biosimilar entry increased by an average of 88.9%, 14.6%, and 22.4%, respectively. However, introduction of (multiple) biosimilar competitors did not necessarily translate into increase in treatment access for all three molecules across some European countries indicating a shift in utilization from one molecule towards the other(s). Conclusion: Overall, this study revealed that biosimilar entry results in increased utilization and price reduction, although at a heterogenous rate among TNF-alpha inhibitors. Observed trends in market shares indicate a biosimilar first-mover advantage whereas pricing strategies considered to be anti-competitive can limit market uptake.

Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA.

Etanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK. Biologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan-Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication. A total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year. In one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.

Cost-Utility Analysis of Biologic Disease-Modifying Antirheumatic Drugs for Patients With Psoriatic Arthritis in Thailand

ObjectivesThis study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). MethodsA decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed. ResultsAll 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor. ConclusionsAt the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.

Real-world use of an etanercept biosimilar including selective versus automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.

ObjectiveBiosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic vs selective.MethodsData from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch.ResultsOf 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan–Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 vs 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area vs 0.4 ± 0.6 in the automatic switch area.ConclusionThe ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.

OA14b Etanercept originator versus its biosimilar (SB4) for the treatment of rheumatoid arthritis. Are they truly similar?

Abstract Background/Aims Etanercept biosimilar SB4 (ETN-B) showed comparable efficacy to its biologic originator (ETN-O) among biologic-naïve patients with rheumatoid arthritis (RA) in randomised controlled trials. Subsequently, a nationwide guideline in the United Kingdom (UK) obligated the prescription of biosimilars in 2016, resulting in significant cost-savings to the NHS. However, real-world evidence comparing ETN-O and ETN-B is limited. This analysis aims to compare the effectiveness of ETN-O versus ETN-B amongst biologic-naïve patients with RA treated in routine clinical practice in the UK. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included patients starting their first biologic (ETN-O or ETN-B), recruited since 2010, with at least one follow-up. Baseline data are collected at start of therapy, including patient demographics and disease activity. Follow-up data are collected six monthly for the first three years and annually thereafter, including changes in disease activity and anti-rheumatic therapy. Key outcomes assessed were change in Disease Activity Score for 28-joints (DAS28), DAS28 remission, EULAR treatment response, change in Health Assessment Questionnaire (HAQ), and minimal clinically important difference (MCID) in HAQ. Drug retention was explored using Kaplan-Meier and Cox-regression analyses, along with reasons for treatment withdrawal. Multiple imputation was used to account for missing data and confounding by indication was accounted for using propensity-decile adjustment. Results This analysis included 1927 patients with RA starting their first biologic therapy: 996 (52%) ETN-O and 931 (48%) ETN-B. At six-months, change in DAS28 and HAQ were similar between therapies (Table). There were no differences in key imputed propensity adjusted outcomes (odds ratio [95% confidence interval]): DAS28 remission: 0.90 (0.7-1.1, p = 0.3); MCID in HAQ: 0.86 (0.7-1.1, p = 0.3) and EULAR treatment response: 0.96 (0.8-1.2, p = 0.8). One-year retention rates were 69% (95% CI: 66-72) for ETN-O and 70% (95% CI: 67-73) for ETN-B and the main reasons for treatment withdrawal were adverse events and ineffectiveness for both drugs. Conclusion This analysis is the first to our knowledge to show similar outcomes amongst biologic-naïve patients with RA treated with either ETN-O or ETN-B using real-world data, which brings further evidence for similarity between the drugs. Disclosure A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

OA14a Outcomes after switching from etanercept originator to its biosimilar (SB4) for the treatment of rheumatoid arthritis

Abstract Background/Aims Following the etanercept biosimilar SB4 (ETN-B) launch in the UK in 2016, nationwide guidelines encourage patients switch from the biologic originator (ETN-O) to ETN-B, known as non-medical switching (NMS). However, the long-term implications of NMS have not yet been analysed nationally among patients with rheumatoid arthritis (RA). This analysis aims to evaluate treatment outcomes and drug retention after patients with RA are switched from ETN-O to ETN-B in routine clinical practice in the UK. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included all patients who switched from ETN-O to ETN-B since 2016. Disease activity was assessed at the time of switch and after six months. Key outcomes included change in disease activity (DAS28), DAS28 remission and EULAR treatment response. Drug retention was analysed using Kaplan-Meier and treatment withdrawal reasons were explored for all patients who switched to ETN-B, as well as (1) patients who switched-back to ETN-O, (2) patients who changed to a non-ETN biologic, (3) patients discontinuing all biologic therapy. Multiple imputation was used to account for missing data. Results 1160 patients with RA switched from ETN-O to ETN-B. Of the 919 (79%) with available DAS28 data, there was no change in six-month DAS28 score following switch (median: 0, IQR: -0.8, 0.7). After a median follow-up of 1.8 years (IQR: 1.0, 2.3), most patients remained on ETN-B (N = 844, 73%) with the main treatment withdrawal reason being ineffectiveness (N = 139, 44%). Among those who discontinued ETN-B, 133 (11%) patients switched-back to ETN-O and 98 (8%) patients changed to a non-ETN biologic; both primarily due to ineffectiveness (Table). Lastly, 85 (7%) patients discontinued all biologic therapy mainly due to adverse events (N = 50, 59%). Conclusion This analysis has demonstrated sustained effectiveness after switching from ETN-O to ETN-B using real-world nationwide data. Among the sub-cohorts of patients who discontinued ETN-B, differences were observed regarding the frequency and reasons for treatment withdrawal. These results will support UK rheumatologists and patients with treatment decisions, assist quality improvement projects to reduce drug withdrawals and refine biologic treatment delivery in the UK. Disclosure A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

Effectiveness of SB4 Transition from Originator Etanercept in Rheumatoid Arthritis and Axial Spondyloarthritis: A Subgroup Analysis from the BENEFIT Study.

The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors. A prospective study for up to 6 months following transition was conducted. Outcome measures of interest include clinical characteristics at time of transition and disease activity scores (Disease Activity Score-28 [DAS28] for RA, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] for axSpA) over time and safety. One-hundred and eleven subjects (out of the 557 in total enrolled in the study) were derived from 8 Italian sites, including 79 with RA and 32 with axSpA. In both cohorts, the efficacy was maintained at 3 months and 6 months from the transition to the biosimilar with no significant change in mean DAS28 and BASDAI scores: at the end of the 6 months of observation the mean DAS28 and BASDAI was similar to baseline (confidence interval [CI] -0.22, 0.22), while the mean variation of the BASDAI was -0.14. Of note, 100.0% (95% CI 89.1, 100.0) in the axSpA and 90.8% (95% CI 81.5, 95.5) in the RA cohort of patients continued to receive SB4 at month 6 (binary variable with 95% Clopper-Pearson CI). Italian patients with stable RA or axSpA who transitioned from originator Etanercept to SB4 maintained clinical response at 6 months post-transition. Both the cohorts are representative of typical patients with long-standing established diagnoses. Most of the patients transitioned to the same dose regimen of biosimilar as that received for the originator, and the regimen remained unchanged at 6 months, supporting the effectiveness of the transition.

Rapid monitoring of health services use following a policy to switch patients from originator to biosimilar etanercept\u2014a cohort study in British Columbia

BackgroundDrug coverage policies that incentivize switching patients from originator to biosimilar products may result in significant health care savings. Our study aimed to detect early impacts on health services utilization following a mandated switch from originator to biosimilar etanercept in British Columbia (BC), Canada.MethodsWe conducted a prospective, population-based cohort study using linked administrative health data from BC (2010–2020). The policy cohort consisted of patients with inflammatory arthritis who used originator etanercept in 2019, prior to BC’s Biosimilars Initiative switching policy. Three historical cohorts included patients with inflammatory arthritis who used originator etanercept in the years 2016, 2017, and 2018. We compared the daily cumulative incidences of drug refills and outpatient and inpatient services between the policy and historical cohorts. A likelihood ratio sustained (≥ 31 days) at 7.1 or higher compared with the null hypothesis was chosen a priori as a threshold for a potential impact of the policy.ResultsEach cohort contained between 1694 and 1963 patients. We detected several potential impacts: 1) a transient increase in etanercept refills between months three and eight (cumulative incidence difference of + 3.0%); 2) an anticipated increase in visits to physicians of any specialty between months three and eight (+ 2.6%); and 3) an anticipated increase in visits to a rheumatologist from the end of month three onwards (+ 12.8%). The policy had no impact on incidences of switching to a different biologic antirheumatic drug, visits to emergency departments, or admissions to hospitals.ConclusionsOnly transient and/or anticipated increases in drug refills and physician visits were observed during the study period. Additional research on clinical outcomes is recommended to strengthen the evidence that no long-term unintended negative health impacts are associated with BC’s Biosimilars Initiative [switching policy].

Effectiveness and safety of a biosimilar-to-biosimilar switch of the TNF inhibitor etanercept in patients with chronic inflammatory rheumatic diseases.

Background:Biosimilar disease-modifying anti-rheumatic drugs (bsDMARDs) has created a financial incentive to encourage switching to cheaper products.Objectives:We aim to study the effectiveness and safety of a non-medical bsDMARD-to-bsDMARD switch from originator etanercept (ETN) to bsDMARD ETN (SB4) and successive to another bsDMARD ETN (GP2015) in patients with chronic inflammatory rheumatic diseases in a real-life setting.Methods:Retrospective chart review of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) who had been treated with originator ETN and were switched twice to ETN bsDMARD for non-medical reasons thereafter. All patients received ETN 50 mg/week. Disease activity and physical function was assessed every 12 weeks with standardized questionnaires.Results:A total of 100 patients who switched twice [54 RA, 27 axSpA, 19 PsA, mean age 54.3 (15.1), 46% male] were included. Patients with axSpA were younger than RA and PsA patients. Patients with SpA were less likely to receive conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than RA patients. Duration of treatment with originator ETN before the first switch was 3.3 (2.3) years. Retention rate 6 months after the second ETN bsDMARD switch was 89%. Disease activity and physical function scores remained rather unchanged in patients with RA and axSpA longitudinally, while there was some more fluctuation in PsA patients. Six patients lost efficacy and were switched back to originator ETN in month 6 (n = 4) or to another mode of action (n = 2). There were 14 adverse events (AE) reported in eight patients. One patient re-administered bsDMARD GP2015 successfully 3 months after healing of mucosal erosions.Conclusion:No relevant change in disease activity and physical function were observed in a non-medical bsDMARD-to-bsDMARD switch scenario. The retention rate after switches from originator ETN to two ETN bsDMARD was close to 90%. Multiple switches resulted in a high adherence rate without clinically important efficacy or safety signals.

Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden.

ObjectivesTo compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch.MethodsPatients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors.ResultsIn total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy.ConclusionThis large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.

Incidence of and Reasons and Determinants Associated with Retransitioning from Biosimilar Etanercept to Originator Etanercept.

BackgroundPatients in clinical practice are transitioned from originator etanercept (OR-ETA) to biosimilar etanercept (BS-ETA), but some subsequently retransition. Insights into the incidence of and reasons for retransitioning and the characteristics of these patients could help clinicians successfully introduce biosimilars.ObjectiveOur objective was to assess the incidence of and reasons for retransitioning from BS-ETA to OR-ETA in patients with a rheumatic disease (RD) and to explore the determinants thereof.MethodsThis cohort study included all patients with RD who had transitioned from OR-ETA to BS-ETA in a large hospital in the Netherlands in 2016. The incidence of retransitioning to OR-ETA and the 1-year persistence with BS-ETA were assessed using the Kaplan–Meier estimator. Reasons for retransitioning were classified as related to (1) efficacy, (2) adverse events, (3) the administration device, and (4) other. Determinants for retransitioning, including baseline and treatment characteristics, were assessed in a nested case–control study using conditional logistic regression.ResultsWe included 342 patients (median age 57.8 years; 53.5% females). At 1 year after transitioning, 9.4% of patients had retransitioned to OR-ETA and 69.7% were persistent with BS-ETA. At the end of follow-up (median 4.4 years), 47 patients (13.7%) had retransitioned to OR-ETA. The median time until retransitioning was 0.55 years (interquartile range 0.2–1.3). Most patients (n = 34 [72.3%]) retransitioned because of a (perceived) loss of effect, followed by adverse events (23.4%). In total 3.8% of patients switched to another biological treatment or a Janus kinase inhibitor; 17.1% of patients discontinued BS-ETA without retransitioning or switching within the first year. Univariate determinants for retransitioning included initiating corticosteroids or intensifying immunomodulator treatment (odds ratio [OR] 2.37; 95% confidence interval [CI] 1.03–5.45) and the number of visits to the rheumatology department (OR 2.06; 95% CI 1.55–2.74). In the multivariate analysis, only the number of visits to the rheumatology department remained significantly associated with retransitioning (OR 2.19; 95% CI 1.60–3.01).ConclusionWhen introducing a biosimilar in clinical care, clinicians should anticipate that one in seven patients will retransition to the originator. A (perceived) loss of effect was the most frequently reported reason for retransitioning. Patients who visited the rheumatology department more frequently had an increased risk of retransitioning, which is likely to be related to patients reporting a loss of effect and to adverse events resulting in more visits to the rheumatology department.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-021-00501-x.

Efficacy and Safety of Etanercept Biosimilars Compared With the Originator for Treatment of Juvenile Arthritis: A Prospective Observational Study.

ObjectiveAnalysis of etanercept biosimilars in pediatric patients with juvenile idiopathic arthritis (JIA) in comparison with the etanercept originator in terms of efficacy and safety.MethodsPatients diagnosed with JIA who started treatment with either the etanercept originator or a biosimilar after January 1, 2017, were selected from the German BIKER registry (Biologics in Paediatric Rheumatology Registry). Furthermore, patients who started therapy with the originator and switched to a biosimilar during the course of therapy were identified. For both patient groups, disease activity and safety were examined and compared separately.ResultsAfter January 1, 2017, 348 patients started treatment with the etanercept originator (n = 293) or a biosimilar (n = 55). Another 57 patients switched to a biosimilar during the course of therapy. A significant decrease or a stable remission of disease activity was observed in both patient groups. The safety profiles were comparable, and frequencies and types of adverse events (AEs) and serious AEs were similar in patients starting therapy with the originator or a biosimilar. Only injection site reactions occurred slightly more frequently under biosimilar therapy, without having an impact on therapy adherence. In patients who switched therapy, the AE rate per 100 patient‐years was comparable before (26.4) and after (32.1) the switch.ConclusionIn patients with JIA who require treatment with etanercept, the originator is still used much more frequently. However, our study highlights the equivalence of etanercept biosimilars for therapy for JIA. Increased use of these biosimilars in pediatric patients can therefore be recommended without hesitation.

The use of biosimilars as a new approach to the treatment of rheumatoid arthritis

The article discusses various options for the management of patients with rheumatoid arthritis (RA) in accordance with modern foreign and domestic recommendations. Data on the possibility of achieving an effect on the background of monotherapy with methotrexate (MT) are presented and options for more active therapy are discussed. The authors compare the effectiveness of sequential change of basic anti-inflammatory drugs (DMARDs), sequential addition of DMARDs to MT, treatment with a triple combination of DMARDs with an inadequate response to MT or in the debut of therapy, combination of DMARDs and biological drugs. According to the study data, in cohorts of patients with equal clinical effectiveness of the triple combination of DMARDs and the combination of DMARDs with biological drugs, however, the severity of the progression of destruction in the joints of the hands and feet is less when using biological agents. It was noted that the evaluation of the effectiveness of the double / triple combination of DMARDs was carried out in open observational studies, which has less evidence value than randomized controlled double-blind placebo-controlled trials (RCTs) for the assessment of biological drugs. Despite the importance of implementing biological drugs in clinical practice, their high cost limits their use by patients. Registration in the Russian Federation of the first biosimilar of etanercept (ETN) - the drug Erelzi is important for the treatment of patients with RA. The article describes the advantages of original ETN (tumor necrosis factor ainhibitor - iFNO a) over other iFNO a, which are monoclonal antibodies to this cytokine. The article presents data on the equivalence of the ETN biosimilar registered in the Russian Federation (Erelzi) with the original ETN in terms of clinical efficacy, safety and immunogenicity. The comparability of drugs in terms of the frequency of adverse events was demonstrated. It is shown that switching from the original ETN to its biosimilar allows you to maintain the effect, not accompanied by an increase in the frequency of intolerance or immunogenicity. It is indicated that Erelzi is registered in the Russian Federation for the treatment of RA, various variants of axial spondylitis, psoriatic arthritis, psoriasis and juvenile idiopathic arthritis.