This sub-analysis of the PROPER study aimed to evaluate outcomes following the transition from reference adalimumab (ADL) to SB5 (Imraldi^™) in routine clinical practice in Spanish patients with rheumatoid arthritis (RA). Adult Spanish patients (n = 73) with RA who initiated SB5 as part of routine clinical practice following treatment with reference ADL were recruited. Outcome measures included persistence on SB5, clinical characteristics, and disease activity scores at the time of transition to SB5 treatment, clinical management over time, and safety. At Week 48, the Kaplan-Meier [95% confidence interval (CI)] estimate of the probability of persistence on SB5 after switching from reference ADL was 0.84 (0.73–0.90) and 83.6% (46/55) of patients were in remission or had low disease activity. The majority of patients [83.6% (61/73)] experienced no disease flare during the study period and reported that the injection was “simple or very simple” to administer (baseline: 66.7%; Week 48: 69.0%) and were generally “satisfied or very satisfied” with the duration of the injection. In total, 21 patients (21/73, 28.8%) reported at least one drug-related adverse event, which were mild in most cases (17/21, 80.9%). In a Spanish cohort of patients with RA transitioning from reference ADL to SB5, the probability of SB5 persistence was high and treatment effectiveness was maintained for up to 48 weeks. There were no new safety signals and SB5 was well tolerated. These findings suggest that there is no evidence to mitigate against transition from reference ADL to SB5 in patients with RA (Clinicaltrials.gov listing: NCT04089514).

Routine regulatory requirements for large comparative efficacy trials (CETs) to support marketing approval of monoclonal antibody (mAb) biosimilars have been the focus of extensive debate in the last few years. This review examines the mounting evidence, accumulated over the past decade, focusing on relevant literature and data published in the European Product Assessment Reports (EPARs) for the fifteen anti-TNFα biosimilars approved to date. The potential for residual uncertainties that may require resolution through CETs following comparative physico-chemical, in-vitro potency, and single dose studies in healthy subjects is examined. It is noted that structural and physicochemical differences between biosimilars and reference products are detectable using modern analytical methods at levels well below those that could impact clinical outcomes, and that in vitro potency testing is fully capable of revealing clinically relevant differences. Additionally, comparative pharmacokinetic studies in healthy participants provide a sensitive assessment of potential differences in drug exposure and immunogenicity. The added value of CETs is further questioned in the light of the fact that anti-TNFα’s display a flat dose-response relationship, meaning that unlike cell-based assays, CETs have limited sensitivity to detect potency differences. Initial concerns about extrapolating data from rheumatoid arthritis studies to support marketing approval of other indications such as inflammatory bowel disease for which not all anti-TNFα’s are effective have been alleviated by post-approval studies. Additionally, as of the end of 2024, no cases where clinical efficacy data were necessary to resolve residual quality concerns have arisen following regulatory assessment of 56 mAb biosimilars and fusion proteins. CETs add significant cost and delay to the development of biosimilars and the time is now ripe to re-examine the need for these CET’s and for further evolution in regulatory thinking.

The aim of biosimilars is to alleviate the financial burden of biological medicinal products. A most relevant challenge for emerging countries is how to select the best option available. In most cases, price is the major determinant, as budgets are chronically scarce. However, initial savings due to price reductions can be overridden if there is a lack of supply due to product shortages or withdrawals. These events can be prevented by a best-value strategy. According to the concept of best-value medicinal products, price is only one of the various criteria to be considered. The purpose of the present paper is to provide suggestions of criteria that can be useful for selecting the best-value biological in emerging countries. Six criteria, that are not limitative, have been selected as follows: standards of regulatory approval, quality of the product, good distribution practices, security of supply, pharmacovigilance, and price.