Biosimilar drugs are biological medicines that are very similar to another biological medicine (reference drug or originator drug) already approved, in terms of structure, biological activity and efficacy, safety and immunogenicity. Before their approval, they must meet regulatory requirements that are specifically determined by regulatory agencies. When required, clinical trials comparing the efficacy and safety of biosimilars and originators are usually done in the most sensitive indication or indications, on enough patients to guarantee statistical confirmation of equivalence, and later extrapolated in view of the results of comparability to other indications of the original medication.
When approval for a biosimilar is granted in the European Union (EU), additional systematic switch studies are not required to support interchangeability at prescriber level; interchangeability means the biosimilar can be used instead of its reference product (or vice versa) or one biosimilar can be replaced with another biosimilar of the same reference product. Since September 2022, this joint statement of the European Medicines Agency (EMA) and the Heads of Medicines Agencies applies to all the EU Member States. Decisions regarding substitution (the practice of dispensing one medicine instead of another medicine without consulting the prescriber), are not within the remit of EMA and are managed by individual Member States .
Switching from reference biosimilars in patients with well-controlled disease, as opposed to automatic substitution, requires participation of prescribers and agreement by patients, but is highly encouraged in many healthcare systems, especially when economically advantageous.
Data from registries indicate that efficacy and drug survival of biosimilars in biological-naïve patients are similar to those of the originals; the 1-year retention rates in the DERMBIO registry were 0.92 for both the adalimumab biosimilar and the adalimumab originator cohorts, but this study did not include patients switching from originator to biosimilar adalimumab .
According to access regulations in Spain, the vast majority of biological-naïve patients with moderate to severe psoriasis that qualify for biological treatment are required to start with a biosimilar (usually adalimumab) and switching to biosimilar adalimumab was required for most patients who were receiving adalimumab originator with adequate response. Following switching, response is maintained in most patients; loss of response can be attributed to nocebo effect in some cases and can be reverted by switching back to the reference biological in others.
López-Ferrer A et al. carried out a multicentre retrospective observational study in 581 patients with moderate to severe plaque psoriasis, consecutively treated according to clinical practice with biosimilar adalimumab, in 17 Spanish hospitals between October 2016 and February 2021 . Drug survival from start of treatment to last visit when discontinuation due to lack/loss of efficacy or adverse events was recorded and analysed with Kaplan-Meier curves. Total follow-up was recorded, and univariate and multivariate analyses with Cox proportional hazards regression model were conducted.
In this study, 71% of patients started biosimilar adalimumab without switch (86% of them were biological-naïve), and 27% of patients overall had concomitant psoriatic arthritis. The mean (SD) PASI value at the start of the adalimumab biosimilar was 9.5 (5.6) for biological-naïve patients and 2.0 (4.0) for patients who were switched from reference adalimumab to biosimilar. The mean duration of treatment the original drug before switching to a biosimilar was 5.9 years; consequently, these patients were a selected population with long-term good response and unlikely to develop anti-drug antibodies.
According to the study, the treatment was withdrawn for lack/loss of improvement in 103 patients (18%) and for treatment-related adverse events in 16.
On univariate analysis, increased drug survival of adalimumab biosimilar in their patients with moderate to severe plaque psoriasis was associated with male sex (HR = 1.874, p < 0.001), age ≤ 65 (HR = 1.673, p = 0.012), coexisting psoriatic arthritis (HR = 2.080, p = 0.001) and switch from the originator (HR = 6.153, p <0.001). These associations were confirmed in multivariate analysis.
The cumulative probability of adalimumab survival at 1 year was 0.91 for patients who switched from adalimumab originator and 0.52 for patients who started on biosimilar adalimumab. The cumulative probability of adalimumab survival at 1 year in our previous Spanish real-world study  was greater than that of patients who started on biosimilar adalimumab in the present study (0.69 vs 0.52, respectively), and the median survival time was more than double (30.5 vs 12.6 months, respectively). Fewer biological alternatives with superior efficacy to adalimumab were available at the time those studies were performed, and the goals of treatment have now become more ambitious.
The cumulative drug survival probability of patients who switched from adalimumab originator was 0.86 at 2 years, as could be expected from a population of patients with long-standing control of disease, depleted of patients who had developed primary/ secondary failure or anti-drug antibodies to originator adalimumab, and thus unlikely to develop anti-drug antibodies to biosimilars.
Conflict of interest
The authors of the research paper  reported conflict of interest, including personal fees for participation as an advisory board member, consultant and/or speaker, and grants/research support for participation in clinical trials sponsored by various pharmaceutical companies.
For full details of the authors’ conflict of interest, see the research paper .
Abstracted by Lluis Puig, MD (Hon), PhD, Director, Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Professor, Universitat Autònoma de Barcelona School of Medicine, Barcelona, Spain.
Readers interested to learn more about biosimilar adalimumab are invited to visit www.gabi-journal.net to view the following manuscript published in GaBI Journal:
Systematic analysis of injection site pain and reactions caused by subcutaneous administration of the adalimumab biosimilar FKB327 versus the adalimumab reference product via different delivery method
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1. López-Ferrer A, Vilarrasa E, Armesto S, et al. Drug survival of adalimumab biosimilars in real-world treatment of psoriasis: a Spanish multicenter study. Dermato Ther. 2022;35(11):e15831.
2. GaBI Online - Generics and Biosimilars Initiative. EMA calls for biosimilar interchangeability across the EU [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Jan 20]. Available from: www.gabionline.net/biosimilars/general/ema-calls-for-biosimilar-interchangeability-across-the-eu
3. Loft N, Egeberg A, Rasmussen MK, et al. Outcomes following a mandatory nonmedical switch from adalimumab originator to adalimumab biosimilars in patients with psoriasis. JAMA Dermatol. 2021;157(6):676-83.
4. Vilarrasa E, Notario J, Bordas X, et al. ORBIT (outcome and retention rate of biologic treatments for psoriasis): a retrospective observational study on biologic drug survival in daily practice. J Am Acad Dermatol. 2016;74(6):1066-72.
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