Clinical value beyond price alone: anti-TNF biosimilars enable early treatment
Biosimilars can be effective in reducing the cost burden of TNF-α inhibitors (anti-TNF) in the treatment of immune-mediated inflammatory diseases (IMIDs).
- Early anti-TNF treatment provides clinical and radiologic benefits in patients with rheumatoid arthritis (RA), improving both quality of life and clinical outcomes
- Anti-TNF biosimilars help reduce treatment costs, enabling patients to access treatment earlier in their disease course
- The availability of TNF-α inhibitor biosimilars have impacted guideline recommendations, with the UK NICE guidelines now recommending earlier biologic treatment, providing early treatment access to more patients
Over the last 20 years, significant improvements in IMID therapy have been observed with the introduction of disease modifying drugs (DMARDs), especially biologic DMARDs (bDMARDs)1.
Compared with conventional synthetic DMARDs (csDMARDs), bDMARDs offer1:
- improved therapeutic responses
- improvements in health-related quality of life
- reductions in disability
- decreased mortality
Anti-TNFs are the most prescribed bDMARDs, controlling joint inflammation and preventing or delaying RA-associated bone erosion (Figure 1)1.
Access to biologic agents is a key consideration in improving treatment and outcomes for patients with rheumatic diseases. As treatment cost is a barrier to effective bDMARD use, biosimilar DMARDs provide a new route to achieving treatment goals – leading to significant decreases in reimbursement prices, widening patient access, and reducing treatment inequalities (Figure 2)1,3–5.
In the European Union, more than 60 biosimilars have been approved for use, with several others currently under evaluation6.
Increasing evidence demonstrates that early RA diagnosis, prompt treatment initiation, and early achievement of remission are the major predictors of clinical, functional, and radiographic outcomes7.
The long-term outcomes of early DMARD treatment in patients with RA have been reported over 20 years. Patients receiving treatment within 6 months of symptom onset have a significantly lower risk of functional disability compared with later treatment (>6 months)8.
Such findings support the concept of a therapeutic ‘window of opportunity’, demonstrating that earlier treatment leads to improved and sustained outcomes. Patients receiving later treatment report higher radiologic scores and increased functional disability over time compared with those receiving earlier treatment8.
For patients with severe RA and a high risk of developing rapid joint destruction, addition of biosimilar DMARD therapy during the early disease stages provides significant clinical benefit, particularly with respect to radiographic progression9.
Current clinical attitudes favour earlier use of biologics in patients with high disease activity despite csDMARD therapy10.
Earlier addition of a biosimilar DMARD to standard csDMARD therapy is associated with a reduction in direct and indirect costs per patient10. Moreover, the clinical value of highly effective anti-TNF biosimilar DMARD therapy, added to the benefits of lower acquisition costs, are expected to improve therapeutic choice in less severe disease10.
Select biosimilar DMARDs are already providing substantial cost savings in some European countries. For example, Denmark obtained a 64% discount following a mandatory nationwide switch from the branded infliximab biologic to the associated biosimilar4.
Therapy with DMARDs should be started as soon as the diagnosis of RA is made12
The trend for biosimilar DMARDs to reduce the average cost per patient, whilst also providing long-term benefits in clinical outcome, may result in expanded patient access to treatment and significant cost savings within tightening restrictions to healthcare budgets10,11.
International guidelines, including those from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), highlight that early treatment is a mainstay of any management approach for RA12,13.
In addition, the ACR advocates use of the most appropriate, cost-effective treatment option, including biosimilar DMARDS; treatment switching in stable patients is considered reasonable if cost savings are available13.
For the first time in the UK, adalimumab, etanercept, infliximab, abatacept or their respective biosimilar DMARDs have been recommended for the treatment of moderate RA (in combination with methotrexate). Previously, NICE recommended biologic treatments for severe disease only; guidance was reviewed following recent clinical trial evidence suggesting biologics provide similar benefits for both moderate and severe disease14.
- Manova M, Savova A, Vasileva M, Terezova S, Kamusheva M, Grekova D, et al. Comparative Price Analysis of Biological Products for Treatment of Rheumatoid Arthritis. Front Pharmacol. 2018;9:1070–1077.
- Rheumatoid Arthritis. Mayo clinic. Available at https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648. Accessed 20 July 2021.
- Schulze-Koops H, Skapenko A. Biosimilars in rheumatology: A review of the evidence and their place in the treatment algorithm. Rheumatology. 2017;56:iv30–iv48.
- Kim HU, Alten R, Avedano L, Dignass A, Gomollón F,·Greveson K, et al. The Future of Biosimilars: Maximizing Benefits Across Immune‑Mediated Inflammatory Diseases. Drugs. 2020;80:99–113.
- Smolen JS, Goncalves J, Quinn M, Benedetti F, Lee JY. Era of biosimilars in rheumatology: reshaping the healthcare environment. RMD Open. 2019;5:e000900.
- EMA website. Available at: ema.europa.eu/medicines/. Accessed 20 July 2021.
- Monti S, Montecucco C, Bugatti S, Caporali R. Rheumatoid arthritis treatment: the earlier the better to prevent joint damage. RMD Open. 2015;1:e000057.
- Gwinnutt JM, Symmons DPM, MacGregor AJ, Chipping JR, Marshall T, Lunt M, et al. Twenty-Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients with Rheumatoid Arthritis. Results From the Norfolk Arthritis Register. Arthritis Rheumatol. 2017;69(8):1566–1575.
- Atsumi T, Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, et al. Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial. Ann Rheum Dis. 2017;76:1348–1356.
- Patel D, Shelbaya A, Cheung R, Aggarwal J, Park SH, Coindreau J. Cost-Effectiveness of Early Treatment with Originator Biologics or Their Biosimilars After Methotrexate Failure in Patients with Established Rheumatoid Arthritis. Adv Ther. 2019;36:2086–2095.
- Müskens WD, Rongen-van Dartel SAA, van Riel PLCM, Adang EMM. Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve? J Rheumatol. 2020 Nov 1;jrheum.200565. doi: 10.3899/jrheum.200565. Online ahead of print.
- Smolen JS, Landewé R, Bijlsma J, Burmester G, Dougados M, Kerschmaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79:685–699.
- ACR Health policy Statement, 2021. Available at: rheumatology.org/Portals/0/Files/ACR-Health-Policy-Statements.pdf. Accessed 20 July 2021.
- NICE, TA715. Adalimumab, etanercept, infliximab and abatacept for treating moderate rheumatoid arthritis after conventional DMARDs have failed. 14 July 2021. Available at: www.nice.org.uk/guidance/ta715. Accessed 20 July 2021.
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.
Biosimilars are uniquely placed to change clinical practice in the fields of gastroenterology, rheumatology, and dermatology. The adoption of biosimilars can improve patient access to the most appropriate treatment, at the optimum time, to ensure the best possible long-term disease outcomes.