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Review: Real-World Evidence Confirms Effectiveness and Safety of Adalimumab Biosimilar SB5


The adalimumab biosimilar SB5 was reported to be as safe and effective as the reference product in a review of randomized controlled trials and real-world studies on immune-mediated inflammatory diseases.

The adalimumab biosimilar SB5 was reported to be as safe and effective as the reference product in a review of randomized controlled trials and real-world studies on immune-mediated inflammatory diseases. Product quality was consistent over time with no drift in biological activity, and both patients and healthcare professionals preferred the SB5 injection device over other devices.

Adalimumab is a monoclonal antibody targeting tumor necrosis factor (TNF) alpha, a pro-inflammatory cytokine involved in the pathogenesis of several autoimmune and inflammatory diseases. Adalimumab was originally approved by the US FDA in 2002. It is now indicated for a number of inflammatory disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), psoriasis, Crohn disease (CD), ulcerative colitis (UC), hidradenitis suppurativa (HS), and uveitis. The main patent for the reference adalimumab (Humira) expired in 2016, and adalimumab biosimilars, including SB5 (Hadlima/Imraldi; Samsung Bioepis), first entered the US market in 2023.

syringe and vial | Image credit: Davizro Photography - stock.adobe.com

Image credit: Davizro Photography - stock.adobe.com

The review summarized the randomized controlled trials that supported the approval of SB5 and provided an overview of the available post-approval, real-world data. Adalimumab SB5 gained approval in the European Union in 2017 and the US in 2019 based on evidence including a comparative clinical trial in patients with RA. Its approval was extended by extrapolation to additional indications including JIA, psoriasis, PsA, AS, CD, UC, and HS. A phase 4 study on SB5 in patients with plaque psoriasis aiming to support interchangeability with the reference product is ongoing.

SB5 is available both as a low-concentration formulation containing citrate and as a high-concentration formulation without citrate. Equivalent pharmacokinetic parameters between the low-concentration SB5 and reference adalimumab was demonstrated in a clinical study of healthy subjects, and were confirmed in the comparative efficacy trial. A later study found the high-concentration, citrate-free formulation of SB5 had equivalent pharmacokinetics to the low-concentration formulation. The authors wrote that in randomized controlled trials, there were “no clinically meaningful differences” in safety and equivalent efficacy between SB5 and the reference product, as well as comparable immunogenicity.

Real-world studies: SB5 as effective as the reference product with no new safety concerns

The reviewers noted that real-world data “is an important means to confirm the findings of randomized clinical trials, which are conducted in controlled settings, and to provide data for the extrapolation of the approval of a biosimilar for use in indications held by the reference product.” The pivotal comparative clinical trial was conducted in patients with moderate to severe RA. Real-world studies have provided additional data on the use of SB5 in RA, AS, PsA, inflammatory bowel disease (IBD), psoriasis, HS, and uveitis, and “confirms the effectiveness and safety of SB5,” the authors said.

Real-world, observational studies have studied SB5 in both adalimumab-naïve and experienced patients. Overall, in real-world studies, SB5 was “as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified.”

Observational studies, such as the PROPER Study that collected 48 weeks of data on patients with inflammatory arthritis or IBD (CD or UC) who had switched from the reference product to SB5, found that treatment effectiveness “was maintained throughout the study.”

The reviewers noted that injection site pain was observed more frequently with SB5 treatment compared to the reference product in multiple studies, adding that these observational studies were conducted with the citrate-containing, low-concentration SB5 formulation. Multiple factors, such as pH, volume, excipients, and the injection device could contribute to injection site pain, they said. The clinical equivalence study that compared the 2 formulations found the incidence of injection site reactions was lower with the citrate-free, high concentration formulation (4% vs 11%).

Product quality has been consistent over time

Since biologics are produced by living organisms, biologic drugs from different manufacturing lots may differ from one another in quality attributes, the authors said, adding that monitoring and minimizing these variations is important to ensure effectiveness and safety. According to the authors, the manufacturing process and quality attributes of SB5 “have been tightly controlled and monitored since production started.” They cited an analysis of 93 batches of SB5, which showed TNF binding and neutralizing potency were comparable across batches, ranging from 86% to 108% and 89% to 119%. Critical quality attributes were consistent over time and “well within the acceptable ranges of variation” recommended by regulatory agencies.

Patients and healthcare professionals prefer the SB5 injection device

The SB5 injection pen is different from the reference adalimumab injection pen in its shape, non-slip surface, and smaller needle gauge. The initiation mechanism does not require pushing a thumb trigger button, and there is an audible indicator that “clicks” at the start and end of each dose. An enlarged medication viewing window allows patients to confirm a complete dose was injected. The reviewers cited 2 survey studies that compared the SB5 injection device to either the adalimumab reference product or etanercept reference product injection device. In both of these studies, most patients (78%-79%) and nurses (85%-86%) preferred the SB5 device.

The reviewers concluded the available data supports safety and effectiveness of SB5 across indications of adalimumab, switching from the reference product to SB5 is “feasible,” both patients and health care professionals have preferred the SB5 injection device over other devices, and the availability of the citrate-free, high-concentration SB5 will likely reduce the incidence of injection site pain.


Kay J, Cross RK, Feldman SR, et al. Review of adalimumab biosimilar SB5 in immune-mediated inflammatory diseases. Adv Ther. 2024;41:509-533. doi:10.1007/s12325-023-02737-1

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