Biologics have transformed the management of patients in a number of therapy areas, including gastroenterology, rheumatology and oncology. In dermatology, biologics have been used for more than ten years for the treatment of patients with moderate to severe psoriasis, and the first agent, etanercept, was approved by the National Institute for Health and Care Excellence (NICE) in 2006. The drug was indicated for patients with severe plaque psoriasis, defined by a psoriasis area severity index (PASI) score of 10 or more and a dermatology life quality index (DLQI) score greater than 10. This was followed by approvals for adalimumab in 2008 and ustekinumab in 2009.
In 2013, a systemic review of the efficacy of biologics in moderate to severe psoriasis found that ustekinumab appeared to be the most efficacious and is recommended as a suitable first-line agent for those requiring a biologic in guidance from the British Association of Dermatologists.1 The guideline also recommends that adalimumab is used for patients with co-existing psoriatic arthritis.
While very effective, biologics are expensive, accounting for six of the top ten most expensive medicines prescribed in hospitals. In 2015/16, the National Health Service (NHS) spent £16.8 billion on drugs and is projected to spend more over the coming years. One solution for reducing expenditure on biologics is greater use of biosimilars, which have been defined as “a biological medicine highly similar to another biological medicine already marketed in the EU (the so-called ‘reference medicine’). Indeed, a recent NHS report suggested that greater use of best value biological agents (that is, biosimilars) has the potential to save at least £200–£300 million per year by 2020/21.2 The report set a target that at least 90% of new patients are prescribed the best value biosimilar within three months of its launch and at least 80% of existing patients within 12 months.
Newer biologics for psoriasis
Adalimumab (brand name Humira), which is licensed for both psoriasis and psoriatic arthritis, generated sales of over 18 billion US dollars in 2017 and the first wave of adalimumab biosimilars are expected to be launched in October 2018, Although increased use of adalimumab biosimilars potentially generates enormous savings for the NHS, studies suggest that the newer biologic agents, secukinumab, ixekinumab, brodalumab and guselkumab, are clinically more efficacious than adalimumab,3 etanercept4 and even ustekinumab.5
It is inarguable that both clinicians and patients should have access to the most effective treatments and it seems that a PASI 90, a goal that is easily achievable with the newer agents, may become the new gold standard for biologic therapy. However, the lack of long-term efficacy data for the newer agents warrants a degree of caution in their more widespread adoption.
Evidence on the longer-term use and real world experience of the older biologics in psoriasis has been provided in a recent study based on data captured from a disease register.6 The study compared the effectiveness of etanercept, adalimumab and ustekinumab. The authors found that when low to normal doses of each agent were used, all biologics had the same efficacy. However, in practice, dose increases (due to a lack of response) were more often required for etanercept and adalimumab compared with ustekinumab.
In other words, ustekinumab was the most effective treatment in daily practice.
Whether or not the newer agents are able to maintain effectiveness outside the confines of a clinical trial remains to be seen from registry data. Until such information becomes available, hospital trusts are likely to increase the use of adalimumab biosimilars, thereby permitting the treatment of a larger number of patients who require a biologic. Nevertheless, this approach denies patients access to treatments that can produce a greater level of disease clearance and which have received an endorsement from NICE. A further possible downside is that greater adoption of biosimilars may limit future investment by pharmaceutical companies in the search for even more effective biologics.
Conclusions
It seems that there is no easy solution to the delicate balance between treating more patients with less expensive biosimilars and using more efficacious (albeit more costly) therapies. Furthermore, such decisions are the remit of Governments and should not be left to commissioners, who are likely to be criticised for whichever option they decide upon.
References
1 Puig L et al. J Eur Acad Dermatol Venereol 2014;28(12):1633–53.
2 NHS England. www.england.nhs.uk/wp-content/uploads/2017/09/biosimilar-medicines-commissioning-framework.pdf (accessed June 2018).
3 Blauvelt A et al. J Am Acad Dermatol 2017;76(3):405–17.
4 Langley RG et al. N Engl J Med 2014;371(4):326–38.
5 Thaci D et al. J Am Acad Dermatol 2015;73(3): 400–9.
6 Zweegers J et al. Br J Dermatol 2017;176(4): 1001–9.
