Etanercept biosimilars: real-world and switching evidence
What the evidence shows
- Studies found8 studies: one trial with repeated switching in psoriasis, one trial and one extension with a single switch in rheumatoid arthritis, and five cohorts from routine care in arthritis, in Denmark, the Netherlands, Italy and the UK.
- Repeated switchingEGALITY moved psoriasis patients three times between Enbrel and Erelzi over 18 weeks. Response rates, safety and antibodies were the same as in patients who stayed on one product.
- Biggest studiesDenmark moved 1,621 arthritis patients from Enbrel to Eticovo (Benepali) in 2016. Disease activity did not change. After a year, 83 in 100 switched patients were still on Benepali, against 90 in 100 in an earlier Enbrel cohort; 7 in 100 went back to Enbrel, mostly for subjective reasons. The Dutch Sint Maartenskliniek asked 642 patients to move and 99 in 100 agreed; six months later 90 in 100 were still on Benepali, against 92 in 100 in an earlier Enbrel cohort. A smaller Dutch hospital that let patients choose saw 73 in 100 still on Benepali after a year; once the authors set aside those who stopped for subjective complaints, retention matched the Enbrel cohort.
- Products with evidenceErelzi, Eticovo. No published switching study yet in this register for Nepexto or the Indian and Japanese products.
- What is missingNo study from India or the Gulf. No study in children. Nothing yet in this register on switching between two etanercept biosimilars.
Studies
Trials with repeated switching
Patients switched between Enbrel and the biosimilar more than once, with a control group that stayed on Enbrel. FDA interchangeability decisions rest on this design.
| Study | Disease | Switch | Products | Patients switched | Follow-up | What the authors report |
|---|---|---|---|---|---|---|
| Gerdes 2018 J Eur Acad Dermatol Venereol 2018;32(3):420-427 Multicentre, Europe | Plaque psoriasis | Multiple switches (three) between reference and biosimilar | Erelzi | 196 | 30 weeks (extension to week 52) | PASI 50, 75 and 90 response rates, percent change in PASI and all other efficacy measures similar between the pooled switched and pooled continued arms; safety and immunogenicity comparable. |
PASI 50, 75 and 90 response rates, percent change in PASI and all other efficacy measures similar between the pooled switched and pooled continued arms; safety and immunogenicity comparable.
No study matches this selection.
Trials and extensions with a single switch
Patients on Enbrel in a trial were moved once to the biosimilar, usually at the half-way point, and followed alongside those who stayed.
| Study | Disease | Switch | Products | Patients switched | Follow-up | What the authors report |
|---|---|---|---|---|---|---|
| Bruni 2020 Ther Adv Musculoskelet Dis 2020;12:1759720X20964031 Florence and Siena university hospitals, Italy | Rheumatoid arthritis (85), psoriatic arthritis (81), axial spondyloarthritis (33), juvenile idiopathic arthritis (14) and other (7) | Originator to biosimilar | Eticovo | 220 | Median 12.1 months | Cumulative persistence on SB4 99.1%, 88.6% and 64.6% at 6, 12 and 18 months; 50 patients (22.7%) had at least one adverse event, 36 (16.4%) a disease flare; 30 (13.6%) stopped SB4, 11 for safety and 19 for loss of efficacy; 17 of the 30 went back to Enbrel; age was the only predictor of stopping at 6 months. |
| Jaworski 2019 Arthritis Res Ther 2019;21:130 Multicentre | Rheumatoid arthritis | Single switch, reference to biosimilar, at week 24 | Erelzi | 166 | 48 weeks | Switch from reference etanercept to GP2015 at week 24 did not affect efficacy, safety or immunogenicity through week 48. |
| Emery 2017 Ann Rheum Dis 2017;76(12):1986-1991 Extension sites in the Czech Republic and Poland | Rheumatoid arthritis | Single switch, reference to biosimilar (at week 52) | Eticovo | 119 | Week 100 | ACR20 at week 100 79.1% after the switch and 77.9% on continued SB4; other efficacy results including radiographic progression comparable; treatment-emergent adverse events after week 52 in 48.7% and 47.6%; one patient per group developed non-neutralising anti-drug antibodies; 94.7% completed 100 weeks. |
Cumulative persistence on SB4 99.1%, 88.6% and 64.6% at 6, 12 and 18 months; 50 patients (22.7%) had at least one adverse event, 36 (16.4%) a disease flare; 30 (13.6%) stopped SB4, 11 for safety and 19 for loss of efficacy; 17 of the 30 went back to Enbrel; age was the only predictor of stopping at 6 months.
Switch from reference etanercept to GP2015 at week 24 did not affect efficacy, safety or immunogenicity through week 48.
ACR20 at week 100 79.1% after the switch and 77.9% on continued SB4; other efficacy results including radiographic progression comparable; treatment-emergent adverse events after week 52 in 48.7% and 47.6%; one patient per group developed non-neutralising anti-drug antibodies; 94.7% completed 100 weeks.
No study matches this selection.
Real-world cohorts
Switches carried out in hospitals and national programmes, with outcomes taken from registries and patient records.
| Study | Disease | Switch | Products | Patients switched | Follow-up | What the authors report |
|---|---|---|---|---|---|---|
| Muskens 2020 Rheumatol Adv Pract 2020;4(2):rkaa042 Bernhoven hospital, Netherlands (single centre) | Inflammatory rheumatic diseases | Originator to biosimilar (voluntary, shared decision) | Eticovo | 70 | 1 year | 70 of 79 eligible patients agreed to transition (89%); crude one-year retention 73% (95% CI 62 to 83) in the transition cohort against 89% (81 to 95) in the historical cohort (p=0.013), adjusted hazard ratio for discontinuation 2.73; after adjusting for the nocebo effect (subjective health complaints as the reason for stopping) retention was comparable, 86% against 89% (p=0.51). |
| Glintborg 2019 Ann Rheum Dis 2019;78(2):192-200 Denmark, DANBIO registry (nationwide) | Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis | Originator to biosimilar (non-medical, mandatory) | Eticovo | 1,621 | 1 year | Disease activity unchanged 3 months before and after the switch; one-year adjusted retention 83% in switchers, 77% in non-switchers and 90% in the historic cohort; 120 switchers (7%) went back to originator, mainly for subjective reasons. |
| Madenidou 2019 Mediterr J Rheumatol 2019;30(1):69-75 Blackpool Teaching Hospitals, UK (single centre) | Inflammatory arthritis | Originator to biosimilar | Eticovo | 72 | 72 of 104 patients on Enbrel switched to SB4 (69.2%); 73.6% of switched patients stayed on SB4; the authors could not tell whether withdrawals were true failure, nocebo effect or spontaneous flare. Their review of ten observational studies found 14% of 3,184 switched patients stopped SB4. | |
| Tweehuysen 2018 Arthritis Rheumatol 2018;70(9):1408-1418 Sint Maartenskliniek, Nijmegen, Netherlands (single centre) | Rheumatoid arthritis (433), psoriatic arthritis (128), ankylosing spondylitis (64) | Originator to biosimilar (voluntary, opt-out) | Eticovo | 625 | 6 months | Six-month treatment persistence 90% (95% CI 88 to 93) on SB4 against 92% (90 to 94) on originator; adjusted hazard ratio for discontinuation 1.57 (1.05 to 2.36); smaller decreases in CRP (adjusted difference 1.8) and DAS28-CRP (0.15) over 6 months in the transition cohort. |
70 of 79 eligible patients agreed to transition (89%); crude one-year retention 73% (95% CI 62 to 83) in the transition cohort against 89% (81 to 95) in the historical cohort (p=0.013), adjusted hazard ratio for discontinuation 2.73; after adjusting for the nocebo effect (subjective health complaints as the reason for stopping) retention was comparable, 86% against 89% (p=0.51).
Disease activity unchanged 3 months before and after the switch; one-year adjusted retention 83% in switchers, 77% in non-switchers and 90% in the historic cohort; 120 switchers (7%) went back to originator, mainly for subjective reasons.
72 of 104 patients on Enbrel switched to SB4 (69.2%); 73.6% of switched patients stayed on SB4; the authors could not tell whether withdrawals were true failure, nocebo effect or spontaneous flare. Their review of ten observational studies found 14% of 3,184 switched patients stopped SB4.
Six-month treatment persistence 90% (95% CI 88 to 93) on SB4 against 92% (90 to 94) on originator; adjusted hazard ratio for discontinuation 1.57 (1.05 to 2.36); smaller decreases in CRP (adjusted difference 1.8) and DAS28-CRP (0.15) over 6 months in the transition cohort.
No study matches this selection.
Switching evidence is what regulators, tender committees and formulary boards ask for before a change of product. EvySaif prepares interchangeability and switching dossiers and designs real-world studies for biosimilar programmes. Regulatory strategy consulting
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