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The use of biosimilars in Crohn’s disease is steadily increasing due to their cost-effectiveness, efficacy and favourable safety profiles, as demonstrated in recent studies such as iBaSS. Here, Dr João Gonçalves PhD – one of this study’s authors – discusses the team’s findings and the impact he anticipates this new understanding of biosimilar adalimumab having on clinical practice and healthcare policy.
Crohn’s disease is a chronic inflammatory bowel disease (IBD) characterised by relapsing inflammation of the gastrointestinal tract, leading to progressive damage. Patients with Crohn’s disease experience symptoms such as abdominal pain, diarrhoea and fatigue, and can develop long-term complications such as strictures and fistulas.
Biological therapies, particularly those targeting tumour necrosis factor-alpha (TNFα), such as adalimumab, have significantly improved patient outcomes by reducing complications, surgeries and hospitalisations. However, the high cost of these biologics places a substantial financial burden on healthcare systems and patients alike.
Biosimilars are biologic drugs that are highly similar to already approved ‘reference’ biologics and offer a promising solution to reduce healthcare costs. Since biosimilar adalimumab became available in Europe in 2018, it has provided a more cost-effective alternative while maintaining the efficacy and safety profile of the reference product.
How do product transitions affect clinical outcomes and patient experiences?
A recent study by Young et al investigated the clinical outcomes and patient experiences of transitioning from reference adalimumab (brand name Humira) to a biosimilar adalimumab (SB5; brand name Imraldi) and looked to address concerns about multiple product transitions and their impact on patient care and satisfaction.1
iBaSS, a phase IV prospective, randomised, single-blind, crossover study involving adult Crohn’s disease patients at the University Hospital Southampton NHS Foundation Trust, aimed to mimic the real-world transition process between biosimilar and reference adalimumab.1
Eligible patients were those in remission or with mild disease activity who were established on a stable dose of reference adalimumab or SB5. Critical exclusion criteria included planned discontinuation of adalimumab, scheduled surgeries or hospitalisation within 12 months of randomisation, and pregnancy or breastfeeding.
Participants were randomised to two treatment sequences: one group received reference adalimumab followed by SB5, and the other received SB5 followed by reference adalimumab.
The primary endpoint was the proportion of patients maintaining baseline clinical status throughout each treatment period. Secondary endpoints included changes in disease activity, medical treatment, immunogenicity, biochemical markers and safety.
Biosimilar adalimumab study findings
Of 318 pre-screened patients, 112 participants were enrolled, with 94 (83.9%) completing the 48-week trial. The primary endpoint was achieved by 81.8% of participants treated with reference adalimumab and 79.5% treated with SB5, indicating similar efficacy between the two products.
Scores for disease activity, measured by the modified Harvey-Bradshaw Index (mHBI) and biochemical markers, were consistent across both treatment phases.
Patient-reported outcomes, assessed using the IBD-Control questionnaire and Treatment Satisfaction Questionnaire for Medication (TSQM), showed no significant difference in disease control and overall satisfaction between the two products.
However, SB5 was associated with higher injection pain scores, likely due to its citrate-based formulation compared with the citrate-free reference adalimumab.
Adalimumab serum trough levels and anti-adalimumab antibody concentrations remained stable throughout both treatment phases, suggesting no increased immunogenicity with multiple product transitions.
The safety profile of SB5 was comparable to that of reference adalimumab, with similar rates of adverse events and serious adverse events reported in both groups.
This study highlights the clinical equivalence of SB5 to reference adalimumab in treating Crohn’s disease, supporting the use of biosimilars as a cost-effective alternative without compromising patient outcomes.
The findings are significant in healthcare systems aiming to manage the high costs associated with biologic therapies. The availability of biosimilars can potentially increase patient access to effective treatments and reduce financial strain on healthcare budgets.
The strengths and limitations
One of the strengths of this study is its real-world applicability as it closely mimics the transition process between biosimilar and reference products. The crossover design allowed each participant to experience both treatments, providing direct comparative data on patient satisfaction and efficacy.
Moreover, using patient-reported outcomes, such as the IBD-Control questionnaire and TSQM, offers valuable insights into patient perspectives on disease control and treatment satisfaction.
The higher injection pain scores associated with SB5 highlight the importance of considering patient comfort and experience when selecting biosimilar products. Although this difference was generally manageable, it underscores the need for healthcare providers to address potential concerns and support patients through the transition process.
Effective communication and patient education can help mitigate the ‘nocebo’ effect, where negative expectations about a new treatment might lead to perceived or actual adverse effects.
Despite its strengths, the study faced limitations, including underpowering due to recruitment challenges exacerbated by the Covid-19 pandemic. The pandemic disrupted clinical research activities, reducing the number of participants and potentially affecting the generalisability of the findings.
Additionally, the single-blind design, where participants were aware of the treatment they received, could introduce bias, although efforts were made to minimise this through educating and monitoring patients.
Biosimilar adalimumab impact on practice and policy
The findings from this study have several implications for clinical practice and healthcare policy.
First, SB5’s demonstrated equivalence to reference adalimumab supports the broader adoption of biosimilars in clinical practice, potentially leading to significant cost savings for healthcare systems. These savings can be redirected to other areas of patient care, improving overall healthcare delivery.
The study underscores the importance of patient-centred care for healthcare providers in managing transitions between biologics. Ensuring patients are well-informed and supported during the transition can enhance adherence and treatment satisfaction, ultimately leading to better clinical outcomes.
Providers should also be aware of the potential for higher injection pain with specific biosimilar formulations and consider this when discussing treatment options with patients.
From a policy perspective, the study highlighted the need for continued investment in biosimilar development and market competition.
As more biosimilars become available, increased competition can drive costs down further, making biologics more accessible to a broader patient population. Policymakers should also consider implementing strategies to support patients during transitions, such as educational programmes and resources for healthcare providers.
Directions for future biosimilar adalimumab research
While this study provides valuable evidence supporting the use of biosimilar adalimumab in Crohn’s disease treatment, further research is needed to address remaining questions and explore new areas of interest.
Future studies could focus on long-term outcomes of biosimilar use, including the impact of multiple product switches on immunogenicity and clinical efficacy over extended periods.2,3
Additionally, research exploring the nocebo effect in greater detail could provide insights into managing patient expectations and improving treatment experiences.
Qualitative studies, such as patient interviews and focus groups, can offer a deeper understanding of patient perspectives and identify factors influencing treatment satisfaction and adherence.
Another important area for future research is investigating the cost-effectiveness of biosimilars in different healthcare settings and patient populations. Economic evaluations can help quantify the potential savings and benefits of adopting biosimilars, informing healthcare policy decisions and resource allocation.
Conclusions
This study has demonstrated the clinical equivalence and safety of biosimilar adalimumab compared to reference adalimumab in treating Crohn’s disease. The findings support the broader use of biosimilars as a cost-effective alternative to reference biologics, with potential benefits for healthcare systems and patients.
While the higher injection pain associated with biosimilar adalimumab warrants consideration, effective patient education and support can help mitigate concerns and enhance treatment satisfaction.
Overall, the research provides a strong foundation for the continued adoption of biosimilars in clinical practice, contributing to more sustainable healthcare models and improved access to biologic therapies.4–6
Further studies are needed to expand on these findings and address remaining challenges, ensuring that patients receive the best possible care in the evolving landscape of biologics.
Author
João Gonçalves PharmD PhD
Faculty of Pharmacy, University of Lisbon, Portugal
References
- Young D et al. A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS). Int J Clin Pharm 2024;11 May.
- Burisch J et al. Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study. Lancet Gastroenterol Hepatol 2020;5(5):454–64.
- Blackstone EA, Joseph PF. The economics of biosimilars. Am Health Drug Benefits. 2013;6(8):469–78.
- Gisbert JP et al. Current evidence on the use of the adalimumab biosimilar SB5 (Imraldi™): a multidisciplinary perspective. Expert Opin Biol Ther 2022;22(2):109–21.
- Lukas M et al. Switching from originator adalimumab to the biosimilar SB5 in patients with inflammatory bowel disease: short-term experience from a single tertiary clinical centre. J Crohns Colitis 2020;14(7):915–9.
- García-Beloso N et al. Switching between reference adalimumab and biosimilars in chronic immune-mediated inflammatory diseases: a systematic literature review. Br J Clin Pharmacol 2022;88(4):1529–50.
