Abstract
Objectives
To assess patient satisfaction after pharmacy-mediated replacement of the originator etanercept prefilled syringe with its biosimilar prefilled pen.
Methods
Prospective observational study from March to May 2018, to assess satisfaction with the new drug dispensed. Patients were asked to answer a paper questionnaire with three questions: pain at injection site, ease of administration, and overall patient satisfaction with the change, rated on a scale from 1 (not satisfied) to 5 (extremely satisfied).
Results
The questionnaire was given to 134 patients (74 men, 60 women), with an average age of 55 years. 118 patients (88%) were from the Rheumatology Service and 16 patients (12%) from Dermatology. The median treatment duration with etanercept was 61 months. 87 (65%) completed questionnaires were collected. The mean pain score was 3.4. Most patients found administration easy with the biosimilar pen, with an average score of 3.7. Mean overall satisfaction was rated at 3.3, being higher among men, younger patients, and those with shorter duration of treatment.
Conclusions
The change of the original product from etanercept to a biosimilar product was acceptable for most of the patients who responded to the survey. Surveys allow us to determine the opinion and preferences of patients, thus achieving higher satisfaction with their treatment. Further research is needed to evaluate the effect of automatic replacement. A collaborative multidisciplinary switching programme should be implemented based on the feedback provided by patients.
Keywords: BIOSIMILAR, Etanercept, Originator, Patient Satisfaction, drug substitution (process)
Introduction
The World Health Organization defines a similar biotherapeutic product (also known as biosimilar) as a “biotherapeutic product that is similar in terms of quality, safety and efficacy to an already licensed reference product”.1
According to the European Medicines Agency (EMA), “interchangeability refers to the possibility of exchanging one medicine for another that is expected to have the same clinical effect”. There are two different ways of replacement: “switching”, when the prescriber exchanges one medicine with another that is expected to produce the same clinical intent; or “automatic substitution” when a biosimilar is dispensed instead of an originator drug at the pharmacy level without consulting the prescriber. Even if a scientific review is carried by the EMA, allowing interchangeability with the reference medicine is taken at the national level.2 Generally, prescription of biosimilars for treatment-naïve patients is encouraged world-wide. Nevertheless, few EU countries currently support automatic substitution of a biosimilar product for patients on the reference product,3 4 and little is known about the perception of patients about replacement. The aim of this study was to assess patient satisfaction after pharmacy-mediated replacement of the reference etanercept prefilled syringe with its biosimilar prefilled pen.
Methods
The substitution of the originator prefilled syringe with the biosimilar pre-filled etanercept pen was performed in Cabueñes Hospital (Gijón, Spain) from March to May 2018. Patients were eligible for the study if they were over 18 years old, had been previously informed by both their doctor and a pharmacist about the replacement, and had been treated with originator etanercept for at least 1 month. Patients were educated regarding the use of the new device by hospital pharmacists. Hospital pharmacists designed a questionnaire which was distributed from the pharmacy after 2–3 months on biosimilar treatment, and brought back to the pharmacy during the following drug-dispensing appointment. Surveys were anonymous and covered topics on pain, ease of administration and overall patient satisfaction (primary endpoints), rated on a scale from 1 to 5 (1: very painful/very difficult to administer/not at all satisfied; 5: completely painless/extremely easy to administer/extremely satisfied). Information about sex, age, indication and time on originator etanercept was required for subgroup analysis. There was also a blank space available for comments. The study was approved by the hospital ethics committee. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (version 16). Differences between categorical variables were analysed by χ2 test.
Results
Anonymous surveys were conducted on 134 Spanish patients when prefilled syringes of etanercept were substituted at pharmacy level by prefilled pens of biosimilar etanercept: 74 were men (55%) and 60 women (45%), with an average age of 55 years. Most patients were using etanercept to treat rheumatic diseases (n=118; 88%): 52 (39%) treatments for rheumatoid arthritis (RA), 61 (46%) for spondyloarthropathies (35 (26%) for ankylosing spondylitis (AS) and 26 (19%) for psoriatic arthritis (PsA), respectively), and 5 (4%) treatments for juvenile idiopathic arthritis (JIA). Only 16 (12%) patients were using etanercept for psoriasis (P). The median treatment duration with originator etanercept was 61 months (range 1–76) (48 months RA; 72 months JIA, AS and P; 51 months PsA). Only 87 (65%) patients answered the survey. Results are summarised in table 1. Participation rate was higher among patients with spondyloarthropathies (69%) and P (69%). Mean pain score was 3.4, being less painful among patients diagnosed with JIA and P and more painful in patients with RA and AS diseases. Most patients found administration easy with the biosimilar pen, with an average score of 3.7. Overall patient satisfaction was not improved with the switch from originator prefilled syringes to pens of biosimilar etanercept: only 23% were extremely satisfied; 28% very satisfied; 23% satisfied; and 26% partly satisfied or not at all satisfied. Pain was similar among subgroups, being slightly more painful for men and patients treated with prefilled syringes for more than 1 year. Men and people under 55 years old found it easier to use the prefilled pen. No differences were found according to previous treatment duration. Overall satisfaction was higher among men, younger patients, and with shorter duration of treatment. No statistically significant difference was found between the study groups.
Table 1.
Main results of the survey.
| Pain | Ease of administration | Satisfaction | |
| Mean scale rate* (n; %) | |||
| 1 | 12 (14%) | 11 (13%) | 16 (18%) |
| 2 | 12 (14%) | 4 (5%) | 7 (8%) |
| 3 | 15 (17%) | 13 (15%) | 20 (23%) |
| 4 | 26 (30%) | 28 (32%) | 24 (28%) |
| 5 | 22 (25%) | 31 (36%) | 20 (23%) |
| Mean score | 3.4 | 3.7 | 3.3 |
| Subgroup analysis (n/N)† | |||
| Disease (mean score) | |||
| RA (33/52) | 3.2 | 3.5 | 3.0 |
| JIA (1/5) | 5.0 | 5.0 | 5.0 |
| AS (24/35) | 3.2 | 3.8 | 3.2 |
| PsA (18/26) | 3.7 | 4.0 | 3.7 |
| P (11/16) | 3.9 | 3.9 | 3.5 |
| P value | 0.562 | 0.885 | 0.655 |
| Sex (mean score) | |||
| Men (52/74) | 3.4 | 3.9 | 3.4 |
| Women (35/60) | 3.2 | 3.4 | 3.0 |
| P value | 0.874 | 0.263 | 0.264 |
| Age (mean score) | |||
| <55 years old (46/65) | 3.4 | 3.8 | 3.5 |
| ≥55 years old (41/69) | 3.4 | 3.6 | 3.1 |
| P value | 0.699 | 0.662 | 0.643 |
| Time on originator etanercept (mean score) | |||
| ≤1 year (17/24) | 3.2 | 3.7 | 3.4 |
| >1 year (70/110) | 3.4 | 3.7 | 3.2 |
| P value | 0.334 | 0.779 | 0.925 |
*Scale from 1 (very painful/very difficult to administer/not at all satisfied) to 5 (completely painless/extremely easy to administer/extremely satisfied).
†n=number of patients who answered the survey; n=number of patients included in the subgroup.
AS, ankylosing spondylitis; JIA, juvenile idiopathic arthritis;P, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
Discussion
Robust preclinical and clinical trials show that biosimilar etanercept is equivalent to the biooriginator5 and different consensus-based recommendations support the use of biosimilars to treat rheumatological and dermatologic diseases.6 7 Nevertheless, the way of switching from the originator to the biosimilar drug could affect physicians’ and patients’ acceptance.
Despite all the information available, many studies still show some reluctance to use biosimilars among doctors and patients. A German study assessing physician (n=50) and patient (n=261) acceptance of infliximab biosimilars in rheumatoid diseases showed that more than 95% of rheumatologists would prescribe a biooriginator rather than a biosimilar if unrestricted, and only 70% of patients accepted the change.8 This percentage was still lower (56%) when the change was performed with no clinical reason, which is the case in our study. Most guidelines encourage patient empowerment and advise doctors to enable them to manage their illness,6 so they can participate in the treatment decision. When the decision to accept the switch is left to the patients, acceptance rates are increased up to 92%.9 On the other side, lack of acceptance has been linked to a negative perception of the biosimilar, which could carry a re-switch to the originator, generally because of subjective complaints, which is known as the “nocebo effect” of the biosimilar.10 Our study shows that only 26% of patients were not satisfied with the change (score 1–2) in the short term.
According to a survey performed among European physicians,11 most of them found that it was critical (24%) or very important (48%) for the decision about treatment choice (originator or biosimilar) to be made by the doctor together with their patients. These percentages differed by countries, with Spain (33%) being one of the countries with the highest proportion of doctors considering it critical to have the authority to decide about switching.
Some northern European countries such as Denmark12 and Sweden13 performed non-medical switches from originator etanercept to biosimilar and published their results. The Danish study showed that disease activity was unaffected after 3 months of follow-up, but after 1 year the withdrawal rate was almost 20%, mainly due to lack of efficacy. The Swedish experience was similar, with 11% of the patients switching back to the originator etanercept after a median of 2 months. No studies were found evaluating patients’ perception after an automatic substitution from an originator molecule to its biosimilar.
Concerning the change of device, the literature shows patients prefer the autoinjector rather than the prefilled syringe.14 A nurse survey in Europe reported a preference (both for them and their RA patients) for the biosimilar autoinjector compared with the original device.15 Ease of administration should be especially important for patients suffering from a rheumatic disease, for which self-administration of subcutaneous injections can be difficult. However, no difference was noticed among patients with rheumatic diseases and dermatologic patients.
There are some limitations to this study, such as the absence of a control group (satisfaction with the originator product was not measured) and a low response rate, which make the results difficult to interpret. Moreover, the questionnaire was not validated (which could have an impact on validity and reliability) and no distinction was made between patient acceptance of a biosimilar and another (patient-friendly) device, as discussed previously.
Further research is needed in order to evaluate the nocebo effect when automatic replacement is performed. It would be interesting to seek the opinions of physicians about this pharmacy-conducted change, and analyse how their opinion may influence patient information and perception. Collaborative multidisciplinary switching programmes should be implemented based on the feedback given by patients.
ejhpharm-2019-001999supp001.pdf (163.8KB, pdf)
Footnotes
Contributors: All authors contributed equally to this work.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Not required.
Provenance and peer review: Not commissioned; externally peer reviewed.
Data availability statement: No data are available.
References
- 1. World Health Organisation . WHO questions and answers: similar biotherapeutic products. Available: https://www.who.int/biologicals/expert_committee/QA_for_SBPs_ECBS_2018.pdf?ua=1
- 2. Biosimilars in the EU, Information guide for healthcare professionals . Prepared jointly by the European Medicines Agency and the European Commission. Available: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf
- 3. Larkin H, Macdonald J, Lumsden R. Pharmacy-mediated substitution of biosimilars – a global survey benchmarking country substitution policies. Generics and Biosimilars Initiative Journal 2017;6:157–64. 10.5639/gabij.2017.0604.034 [DOI] [Google Scholar]
- 4. La Noce A, Ernst M. Switching from reference to biosimilar products: an overview of the European approach and real-world experience so far. Eur Med J 2018;3:74–81. [Google Scholar]
- 5. Emery P, Vencovský J, Sylwestrzak A, et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 2017;76:51–7. 10.1136/annrheumdis-2015-207588 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Kay J, Schoels MM, Dörner T, et al. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Ann Rheum Dis 2018;77:165–74. 10.1136/annrheumdis-2017-211937 [DOI] [PubMed] [Google Scholar]
- 7. British Association of Dermatologists’ Position Statement on Biosimilars, 2017. Available: http://www.bad.org.uk/shared/get-file.ashx?id=3615&itemtype=document
- 8. Waller J, Sullivan E, Piercy J, et al. Assessing physician and patient acceptance of infliximab biosimilars in rheumatoid arthritis, ankylosing spondyloarthritis and psoriatic arthritis across Germany. Patient Prefer Adherence 2017;11:519–30. 10.2147/PPA.S129333 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Scherlinger M, Langlois E, Germain V, et al. Acceptance rate and sociological factors involved in the switch from originator to biosimilar etanercept (SB4). Semin Arthritis Rheum 2019;48:927–32. 10.1016/j.semarthrit.2018.07.005 [DOI] [PubMed] [Google Scholar]
- 10. Rezk MF, Pieper B. Treatment outcomes with biosimilars: be aware of the nocebo effect. Rheumatol Ther 2017;4:209–18. 10.1007/s40744-017-0085-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Dolinar RO, Reilly MS. Biosimilars naming, label transparency and authority of choice – survey findings among European physicians. Generics and Biosimilars Initiative Journal 2014;3:58–62. 10.5639/gabij.2014.0302.018 [DOI] [Google Scholar]
- 12. Glintborg B, Sørensen IJ, Loft AG, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis 2017;76:1426–31. 10.1136/annrheumdis-2016-210742 [DOI] [PubMed] [Google Scholar]
- 13. Alten R. Preliminary real world data on switching patterns between etanercept, its recently marketed counterpart and its competitor adalimumab, using Swedish prescription registry. Abstract 356. ACR/ARHP Annual Meeting, 2017. [Google Scholar]
- 14. Vermeire S, D'heygere F, Nakad A, et al. Preference for a prefilled syringe or an auto-injection device for delivering golimumab in patients with moderate-to-severe ulcerative colitis: a randomized crossover study. Patient Prefer Adherence 2018;12:1193–202. 10.2147/PPA.S154181 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Thakur K, Biberger A, Handrich A, et al. Perceptions and preferences of two etanercept autoinjectors for rheumatoid arthritis: a new European Union-approved etanercept biosimilar (Benepali®) versus etanercept (Enbrel®) - findings from a nurse survey in Europe. Rheumatol Ther 2016;3:77–89. 10.1007/s40744-016-0035-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
ejhpharm-2019-001999supp001.pdf (163.8KB, pdf)