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Biosimilars: an option to alleviate the heavy burden of immune-mediated inflammatory diseases

Read time: 10 mins
Last updated:16th Jul 2021
Published:16th Jul 2021
Developed by EPG Health for Medthority in collaboration with Biogen®. This content is intended for healthcare professionals only, and it has been funded and reviewed by Biogen® for scientific accuracy.

Biosimilars can be effective in reducing the burden of immune-mediated inflammatory diseases (IMIDs).

  • IMIDs can overwhelm patients and their families, while society and healthcare providers incur significant financial stress
  • Treatment of primary IMIDs with biosimilars can reduce the risk and impact of secondary IMIDs, alleviating the disease burden of IMIDs
  • Biosimilar treatment in IMID co-occurrence requires further investigation

Significant disease burden

Immune-mediated inflammatory diseases (IMID) are characterised by common inflammatory pathways leading to tissue inflammation, which may be triggered by dysregulation of normal immune responses. Common IMIDs include rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), multiple sclerosis (MS), and psoriasis (PsO)1.

IMIDs can cause organ damage, and are associated with diminished quality of life (QoL), increased morbidity and/or mortality2. IMIDs impose a significant burden on millions of people worldwide, while society and healthcare providers incur considerable financial strain3–6. The COVID-19 virus can place some patients with IMIDs at additional risk of severe infection and increased disease burden7.

Common unmet needs reported by patients with IMIDs include limited access to appropriate treatments, delayed initiation of treatment, discontinued treatment, and variable implementation of treat-to-target approaches (T2T) by health care professionals (Figure 1)8–12. Such unmet needs worsen disease burden in patients with IMIDs, with downstream adverse consequences for their families and/or caregivers3–5.

453 - Biosimilars - article fig1.png

Figure 1. Factors contributing to increased disease burden in immune-mediated inflammatory diseases (Adapted8,10–13). IMID, immune-mediated inflammatory diseases.

The burden of IMIDs is worsened by occurrence during working age, with peak onset occurring at 40–50 years of age for RA, 20–40 years of age for ulcerative colitis and Crohn’s disease, and under 40 years of age for PsO14.

IMIDs can cause organ damage, and are associated with diminished quality of life (QoL), increased morbidity and/or mortality2. IMIDs impose a significant burden on millions of people worldwide, while society and healthcare providers incur considerable financial strain3–6.

The risk of developing a second IMID is significantly higher in individuals who have a primary, diagnosed IMID (“poly-autoimmunity”). For example, having a primary IMID imposes on patients a 5–62% increased risk of developing another IMID, and 3–75% increased risk of developing two further IMIDs. Certain pairs of IMIDs co-occur more frequently than others15.

  • Risk of myocardial infarction (MI) increases across some IMIDs, with 69% increased risk in RA, and 41% increased risk in psoriatic arthritis16
  • Patients with PsO are at increased risk of cardiovascular disease17, IBD3,17–19, and uveitis20
  • Patients with IBD are at higher risk of developing PsO, RA, ankylosing spondylitis (AS), MS, or asthma3,18,19,21,22
  • The presence of another IMID raises the risk of surgery and decreases QoL3,18,19,23

The presence of another IMID increases disease burden by increasing the risk of surgery and decreasing disease-specific and general physical quality of life24,25.

Alleviating disease burden with biosimilars

Optimal clinical treatment of IMIDs focuses on control of inflammation, prevention of tissue damage, improvement of quality of life, and long‐term disease remission2. IMID treatment aims to control the primary IMID and reduce the potential risk of a secondary IMID18,26. Targeted biologic medicines have improved clinical outcomes in patients with IMIDs27–30, including improved QoL and reduced incidence of adverse events31–35.

The cost of developing and manufacturing biologics, however, is high36. High cost, combined with stringent national reimbursement criteria governing access to biologics, has led to their underuse throughout Europe14,37. Potentially millions of patients with IMIDs globally are left exposed without accessible treatment options and mounting unmet needs38.

The potential pharmacoeconomic benefits of cost-effective biosimilars is a treatment option for patients burdened with primary and secondary IMIDs39–41. A biosimilar is highly similar to the innovator biologic (reference product), for which similarity has been proven in an extensive comparability exercise, encompassing physical, chemical, biological, and pharmacological properties, including efficacy and safety.

CLICK HERE* to access Biogen®’s Biosimilars Medical Academy

*By clicking on this button, you will be taken to a Biogen® branded product site of promotional nature.

A role for biosimilars in primary IMIDs

Clinical trials of biosimilars aim to show equivalent clinical performance of the biosimilar in relation to the reference biologic, as prespecified on the basis of data from previous clinical trials with the biologic42.

The 52-week NOR-SWITCH extension study demonstrated non-inferiority in disease worsening, adverse events, or immunogenicity between patients with primary IMIDs who maintained the biosimilar CT-P13 and patients who switched from originator infliximab to CT-P13, which supports switching from the reference infliximab to CT-P13 is comparatively safe and efficacious43,44.

The adalimumab biosimilars SB5 and BI 695501 demonstrate equivalent efficacy, and similar safety and immunogenicity to adalimumab in clinical trials in patients with moderately to severely active rheumatoid arthritis, despite treatment with methotrexate45.

Biologics are effective in inducing and maintaining remission in patients with primary IMIDs; however, dose-reducing strategies to alleviate the financial burden of biologics is successful only for a subset of patients; many others are exposed to increased disease burden and reduced quality of life46–48. The more cost-effective nature of biosimilars may mean patients with primary IMIDs can receive the T2T protocol, and be maintained on a biosimilar regimen based on their risk factors and personal needs49. Patients at risk of relapse can continue biosimilar therapy when in remission or experiencing low-disease activity. In single-centre study, clinical remission was achieved in 65.5% of Crohn’s disease (CD) and 75.5% of ulcerative colitis (UC) patients on a biosimilar monoclonal antibody to infliximab (week 14)50. At week 54, the rate of continuous clinical response was 51% in CD and UC49. This approach could improve patient outcomes and reduce disease burden38.

The pharmacoeconomic benefits of biosimilars can extend to patients at risk of developing secondary IMIDs38–40, further reducing the burden on the patient, as shown below39–41.

Anti-TNFα inhibitors and secondary IMID risk in patients with inflammatory bowel disease

In a Danish study, 3,235 patients with a diagnosis of IBD (22.5%) had a diagnosis of at least one IMID18. The most common IMIDs were PsO, asthma, type 1 diabetes, and iridocyclitis18. Co-occurrence of IMIDs increased the risk of surgery in patients with CD18. Increasing age and antimetabolite use were associated with increased risk of developing a secondary IMID (P<0.0001) during follow-up, while being male, of a high socioeconomic status, or treated with an anti-TNFα inhibitor were associated with a reduced risk of developing additional IMIDs (P=0.0034)18.

Anti-TNFα inhibitors and myocardial infarction risk in patients with psoriasis

The use of anti-TNFα inhibitors is associated with a statistically significant reduced risk of MI in patients with PsO by 50% (P=0.003) for 2 months or longer26, compared with patients treated with topical agents. Head-to-head comparisons in the same study showed that anti-TNFα inhibitors were associated with a non-statistically significant lower MI incident rate compared with psoriatic patients treated with oral agents/phototherapy26.

Anti-TNFα inhibitors may have stronger protective effects in the group >60 years compared with the group <60 years26. In adults older than 60 years, the anti-TNFα inhibitors cohort had a significant 68% lower hazard of incident MI (HR 0.32; 95% CI 0.14–0.73) compared with the topical cohort. Older patients are more likely to have type 2 diabetes mellitus; thus, the benefits of anti-TNFα inhibitors may be mediated through improving risk of type 2 diabetes mellitus26.

Conclusions

Immune-mediated inflammatory diseases are a complex cluster of medical conditions triggered by dysregulation of normal immune responses. Targeted biologics have improved outcomes in patients with IMIDs, but the high cost of these medicines, combined with a restrictive regulatory framework, has led to their underuse, potentially worsening the disease burden of IMID in patients and society.

Cost-effective biosimilars may be an option for some patients burdened with primary and secondary IMIDs. Treatment with biosimilars demonstrate equivalent efficacy, safety and immunogenicity, across a range of primary IMIDS, and may have an important role in primary disease remission. Biosimilars improve the risk and impact of secondary IMIDs, further reducing the burden on the patient and their family.

As biosimilars are currently available or in development for several IMIDs, clinicians may incorporate knowledge of the risks of secondary IMIDs into their treatment decisions and preventive care strategies for patients with existing IMIDs. The role of biosimilars in IMID co-occurrence deserves further investigative research.

CLICK HERE* for Biogen®’s biosimilar clinical trial data

*By clicking this button, you will be taken to a Biogen® branded product site of promotional nature.

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Developed by EPG Health for Medthority in collaboration with Biogen who provided some of the content. Medthority received educational funding from the sponsor in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content.

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