tinuation rate for reference etanercept at 1 year at BADBIR was reported to be 30%. The slight difference in discontinuation rate might come from the fact that in our study biologic experienced patients and patients with lower baseline PASI were included. Other studies also suggest no significant differences in risk of discontinuation between SB4 and reference etanercept, not only in psoriasis but also in RA.6,7,14
The 5 patients who stopped SB4 for patient choice or non-compliance may reflect nocebo effects associated with biosimilars. Nocebo effects, patients’ negative anticipation of biosimilar treatment, are often observed in real world settings and result in suboptimal outcomes.10 Such nocebo effect can be managed by obtaining informed consent prior to switching to biosimilars and by educating both HCP and patients to increase awareness on biosimilars.11 Real world evidence on biosimilars can provide additional reassurance to reduce nocebo effect.12
Analysis on reduction in PASI and DLQI at 6 month from the patients with available data showed SB4 either maintained or improved disease activity. This is in line with other studies where similar levels of PASI reduction are observed with SB4 treatment.7,15
While a limitation of this study is that we did not have access to raw data on other biologics in the register for comparison, we were able to compare our findings to previously published BADBIR data on etanercept.
In conclusion, data from BADBIR show that the use of SB4 in clinical practice was effective in patients with psoriasis. As more long-term real world evidence on biosimilars accumulates, confidence in biosimilars will likely be increased, and nocebo effect with biosimilar use may be reduced, thereby helping to realize more fully the cost saving potiential of biosimilars.
The 5 patients who stopped SB4 for patient choice or non-compliance may reflect nocebo effects associated with biosimilars. Nocebo effects, patients’ negative anticipation of biosimilar treatment, are often observed in real world settings and result in suboptimal outcomes.10 Such nocebo effect can be managed by obtaining informed consent prior to switching to biosimilars and by educating both HCP and patients to increase awareness on biosimilars.11 Real world evidence on biosimilars can provide additional reassurance to reduce nocebo effect.12
Analysis on reduction in PASI and DLQI at 6 month from the patients with available data showed SB4 either maintained or improved disease activity. This is in line with other studies where similar levels of PASI reduction are observed with SB4 treatment.7,15
While a limitation of this study is that we did not have access to raw data on other biologics in the register for comparison, we were able to compare our findings to previously published BADBIR data on etanercept.
In conclusion, data from BADBIR show that the use of SB4 in clinical practice was effective in patients with psoriasis. As more long-term real world evidence on biosimilars accumulates, confidence in biosimilars will likely be increased, and nocebo effect with biosimilar use may be reduced, thereby helping to realize more fully the cost saving potiential of biosimilars.
DISCLOSURES
A.E. has received research funding from Pfizer, Eli Lilly, the Danish
National Psoriasis Foundation, and the Kgl Hofbundtmager Aage
Bang Foundation, and honoraria as consultant and/or speaker
from AbbVie, Almirall, Leo Pharma, Samsung Bioepis Co., Ltd.,
Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant,
Bristol-Myers Squibb, and Janssen Pharmaceuticals. G.G. has
been the principal investigator in clinical trials sponsored by
and/or and has received personal fees from AbbVie, Abiogen,
Almirall, Amgen, Bayer, Biogen, Celgene, Eli Lilly, Galderma,
Hospira, Janssen, LEO Pharma, Merck, MSD, Mundipharma,
Novartis, Pfizer, Pierre Fabre, Regeneron, Samsung Bioepis,
Sandoz, Sanofi and Sun Pharma. S.R.F. has received research,
speaking, and/or consulting support from Almirall, Leo
Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho
Dermatology, AbbVie, Samsung Bioepis, Janssen, Lilly, Merck,
Novartis, and Sun Pharma. M.A.R. has served as a consultant
and/or paid speaker for and/or has received research grants and/or honoraria for consulting and/or scientific lectures for and/or
got travel expenses reimbursed and/or participated in clinical
trials sponsored by companies that manufacture drugs used for
the treatment of psoriasis, including Abbott/AbbVie, Almirall,
Amgen, Astellas, Biogen, Biologix, Boehringer Ingelheim,
Celgene, Galderma, Hexal, Janssen-Cilag, La Roche Posay, Leo,
Lilly Pharma, Medac, Merck, MSD, Mundipharma, Novartis,
Pfizer, Sandoz, Sanofi and Takeda Pharmaceutical. J.M.C. has
nothing to disclose. J.G., J.W.K., J.L. and H.S. are full-time
employees of Samsung Bioepis.
The study was sponsored by Samsung Bioepis and Samsung
Bioepis received raw data from BADBIR and performed analyses.
REFERENCES
1. Food and Drug Administration. Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for Industry https://www.fda.gov/media/125484/ download Accessed Oct 31, 2019.
2. European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues https://www.ema.europa.eu/en/documents/ scientific-guideline/guideline-similar-biological-medicinal-products-containing- biotechnology-derived-proteins-active_en-2.pdf Accessed Oct 31, 2019.
3. Kim S, Song J, Park S, et al. Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar. MAbs. 2017;9(4):704-714.
4. Carrascosa J-M, Jacobs I, Petersel D, Strohal R. Biosimilar drugs for psoriasis: principles, present, and near future. Dermatol Ther (Heidelb). 2018;8(2):173-194.
5. European Medicines Agency. Benepali summary of product characteristics. https://www.ema.europa.eu/en/documents/variation-report/benepali-h-c- 4007-x-0016-epar-assessment-report_en.pdf Accessed Oct 31, 2019.
6. Egeberg A, Ottosen MB, Gniadecki R, et al. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol. 2018;178(2):509-519.
7. Gisondi P, Bianchi L, Calzavara-Pinton P, et al. Etanercept biosimilar SB4 in the treatment of chronic plaque psoriasis: data from the Psobiosimilars registry. Br J Dermatol. 2019;180(2):409-410.
8. Burden AD, Warren RB, Kleyn CE, et al. The British Association of Dermatologists' Biologic Interventions Register (BADBIR): design, methodology and objectives. Br J Dermatol. 2012;166(3):545-554.
9. Medicine optimisation dashboard. NHS Trusts https://apps.nhsbsa.nhs.uk/ MOD/AtlasTrustsMedsOp/atlas.html Assessed Sep 18, 2019 10. Rezk MF, Pieper B. Treatment outcomes with biosimilars: be aware of the nocebo effect. Rheumatol Ther. 2017;4(2):209-218.
11. Kristensen LE, Alten R, Puig L, et al. Non-pharmacological effects in switching medication: the nocebo effect in switching from originator to biosimilar agent. BioDrugs. 2018;32(5):397-404.
12. Ebbers HC, Pieper B, Issa A, Addison J, Freudensprung U, Rezk MF. Realworld evidence on etanercept biosimilar sb4 in etanercept-naïve or switching patients: a systematic review. Rheumatol Ther. 2019;6(3):317-338.
13. Warren RB, Smith CH, Yiu ZZN, et al. Differential drug survival of biologic therapies for the treatment of psoriasis: a prospective observational cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2015;135(11):2632-2640.
14. Glintborg B, Loft AG, Omerovic E, et al. 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. Ann Rheum Dis. 2019;78(2):192-200.
15. Pescitelli L, Lazzeri L, Di Cesare A, Tripo L, Ricceri F, Prignano F. Clinical experience with the etanercetanercept biosimilar SB4 in psoriatic patients. Int J Clin Pharm. 2019; 41(1):9-12.
2. European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues https://www.ema.europa.eu/en/documents/ scientific-guideline/guideline-similar-biological-medicinal-products-containing- biotechnology-derived-proteins-active_en-2.pdf Accessed Oct 31, 2019.
3. Kim S, Song J, Park S, et al. Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar. MAbs. 2017;9(4):704-714.
4. Carrascosa J-M, Jacobs I, Petersel D, Strohal R. Biosimilar drugs for psoriasis: principles, present, and near future. Dermatol Ther (Heidelb). 2018;8(2):173-194.
5. European Medicines Agency. Benepali summary of product characteristics. https://www.ema.europa.eu/en/documents/variation-report/benepali-h-c- 4007-x-0016-epar-assessment-report_en.pdf Accessed Oct 31, 2019.
6. Egeberg A, Ottosen MB, Gniadecki R, et al. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol. 2018;178(2):509-519.
7. Gisondi P, Bianchi L, Calzavara-Pinton P, et al. Etanercept biosimilar SB4 in the treatment of chronic plaque psoriasis: data from the Psobiosimilars registry. Br J Dermatol. 2019;180(2):409-410.
8. Burden AD, Warren RB, Kleyn CE, et al. The British Association of Dermatologists' Biologic Interventions Register (BADBIR): design, methodology and objectives. Br J Dermatol. 2012;166(3):545-554.
9. Medicine optimisation dashboard. NHS Trusts https://apps.nhsbsa.nhs.uk/ MOD/AtlasTrustsMedsOp/atlas.html Assessed Sep 18, 2019 10. Rezk MF, Pieper B. Treatment outcomes with biosimilars: be aware of the nocebo effect. Rheumatol Ther. 2017;4(2):209-218.
11. Kristensen LE, Alten R, Puig L, et al. Non-pharmacological effects in switching medication: the nocebo effect in switching from originator to biosimilar agent. BioDrugs. 2018;32(5):397-404.
12. Ebbers HC, Pieper B, Issa A, Addison J, Freudensprung U, Rezk MF. Realworld evidence on etanercept biosimilar sb4 in etanercept-naïve or switching patients: a systematic review. Rheumatol Ther. 2019;6(3):317-338.
13. Warren RB, Smith CH, Yiu ZZN, et al. Differential drug survival of biologic therapies for the treatment of psoriasis: a prospective observational cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2015;135(11):2632-2640.
14. Glintborg B, Loft AG, Omerovic E, et al. 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. Ann Rheum Dis. 2019;78(2):192-200.
15. Pescitelli L, Lazzeri L, Di Cesare A, Tripo L, Ricceri F, Prignano F. Clinical experience with the etanercetanercept biosimilar SB4 in psoriatic patients. Int J Clin Pharm. 2019; 41(1):9-12.
AUTHOR CORRESPONDENCE
Alexander Egeberg MD PhD alexander.egeberg@gmail.com
