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27th June 2024
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.
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.
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.
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.
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.
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.
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.
João Gonçalves PharmD PhD
Faculty of Pharmacy, University of Lisbon, Portugal
27th June 2023
A higher dose of adalimumab is likely to be more effective for obese patients with hidradenitis suppurativa, according to the findings of a small trial.
Adalimumab (ADA) is one of only two biologic therapies, together with secukinumab, approved by the EMA for the management of hidradenitis suppurativa (HS). However, adalimumab dosing is not weight-based and in two phase 3 trials, just over half of the patients assigned to adalimumab 40 mg/week (ADA40) achieved a clinical response.
Given that patients with HS are four times more likely to be obese compared to the general population, there might be an advantage of using a higher ADA dose in HS patients who are either overweight or obese.
In the current study, published in the Journal of Drugs in Dermatology, a team of US researchers evaluated the effectiveness of adalimumab 80 mg/week (ADA80) versus 40 mg, in overweight and obese patients with moderate to severe HS. The team included patients with a body mass index greater than 25 and who were refractory to treatment with ADA40. A dose of 80 mg was administered for at least three months and improvements were assessed using the HS-Physician Global Assessment.
A total of eight patients with a mean age of 37 years (six females) and with a median body mass index of 36.6 were included in the study and were followed for a median of 13.2 months on ADA80.
Patients experienced a greater improvement in the HS-Physician Global Assessment with ADA80 compared to ADA40 (p = 0.01). In addition, all five patients who had their lesion counts documented achieved a HS clinical response, and all eight patients reported improvements in pain, drainage, lesions and the frequency of disease flares.
While acknowledging the limitations from a small sample size, the researchers suggested that their data indicates a benefit increasing the dose of adalimumab in overweight and obese patients with HS.
Earlier this year, a phase 3 trial found bimekizumab to be an effective treatment for patients with hidradenitis suppurativa.
9th June 2021
Adalimumab is effective for children with Crohn’s disease but little is known about the impact of therapeutic monitoring on clinical outcomes.
The clinical symptoms of Crohn’s disease (CD) are similar in adults and children although there is evidence that cases of paediatric CD are on the rise, with one study estimating that the highest incidence, at 23 per 100,000 person-years occurred in Europe.
Endoscopic evidence of mucosal healing is a valuable therapeutic goal that decreases the risk of disease relapse although little is known about the association between mucosal healing and therapeutic levels of biological treatments such as adalimumab.
This prompted a team from the Department of Paediatrics, Samsung Medical Centre, Korea, to examine the relationship between therapeutic drug monitoring of adalimumab and mucosal healing and clinical remission in paediatric patients with CD.
The team prospectively recruited paediatric patients with CD receiving adalimumab maintenance therapy and who underwent routine endoscopic evaluation of mucosal healing and therapeutic drug monitoring. Monitoring assessments were made at four months and then at years one, two and three.
In total, 31 children with a mean age of 14.8 years (74% male) were included in the analysis. After one year of treatment, 26 (83.9%) had achieved clinical remission and 17 (54.8%) had complete mucosal healing.
The mean adalimumab trough levels were higher in patients who had achieved remission compared to those with active disease (7.6 mcg/ml vs 5.1 mcg/ml, remission vs active disease).
Similarly, trough levels of adalimumab were significantly higher in those who achieved mucosal healing after one year (14.2 mcg/ml vs 7.8mcg/ml, mucosal healing vs non-healed, p = 0.03).
Although only 23 children were evaluated after 3 years, adalimumab trough levels remained above 10 mcg/ml and a similar proportion of children maintained mucosal healing (64.3%) and clinical remission (92.9%).
Using receiver operating curves, authors calculated that the optimal cut-off adalimumab trough levels to achieve mucosal healing was 8.18 mcg/ml.
In discussing their findings, the authors commented on the results demonstrated that mucosal healing rates increased when adalimumab was used over the longer term and that the drug maintained its efficacy.
They concluded that there was merit in using therapeutic drug monitoring to guide proactive optimisation of drug levels to achieve the goal of mucosal healing.
Citation
Kim MJ et al. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients with Crohn Disease. JPGN 2021;72:870-6.
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