The treatment of psoriasis has always been a challenge for modern medicine. As a podiatrist working in a dermatology department in the 1990’s I remember the scores of patients queuing for PUVA light treatment and many others receiving regular topical applications to best control their skin problem.
It has long been known that psoriasis is a disease that is immune-mediated and resulted from a mis-appropriated inflammatory response directed towards the skin. This was known as certain drugs such as methotrexate and ciclosporin were understood to alter T cell function and so when administered to patients with psoriasis some showed a positive responses to the disease but often with unpleasant side-effects. Yet, targeted therapies had eluded science until that time.
Around the turn of the millennium a new class of drug was introduced as the first “biological agent”. Entanercept (marketed as Enbrel) was the first drug “designed” specifically to block an inflammatory pathway – that of TNF-α, a cytokine produced by the white blood cells which amplifies the inflammatory response. The clinical results were very encouraging for patients with some showing significant improvement - but not for all.
As we have progressed from the millennium, science has continued to develop and release new biological agents into the market. Each are designed to control or block specific inflammatory pathways – usually cytokines (interleukins) or B cell functions. Consequently, we have seen a mini-revolution in the numbers of these drugs available in psoriasis with significant effects on plaque reduction and clearance with similar effects reported for nail involvement (1) - traditionally a stubborn area to treat. This has not been without problems as they are often expensive, and it is difficult to predict which patients will benefit best from which drug. In addition, as with any new class of drugs, new side-effects are being reported.
Currently, for psoriasis there are a range of these drugs available which have been approved by NIHCE in the United Kingdom (with tricky to pronounce names): adalimumab, etanercept, infliximab, ustekinumab, secukinumab and ixekizumab with others entering the market and awaiting NIHCE approval. The British Association of Dermatologists in 2017 published their latest guidelines on the use of these drugs (2). With the arrival and introduction of new biologicals there has been improvements in patient’s response and a reduction in side effects as more is learned about these agents and how they are best used. Currently, in order for patients to receive these drugs they need to meet certain requirements as laid down by NIHCE guidelines before they can receive these agents through the NHS.
Recently, research has been published which highlights that newer biological agents targeting IL-17 & IL-23 to be most efficacious. Published recently in the British Journal of Dermatology a new drug Guselkumab targets IL-23 has been shown to be a potentially safer and a more effective and convenient drug than adalimumab (3). With time, based on current progress, we can expect more rapid progress in the development of these biological agents. Published studies have reported how these drugs can be expected to clear around 75% of their psoriasis and for many patients even higher, something which would have been considered near impossible in the 1990’s. Ultimately, it means the future for patients with chronic plaque psoriasis is much brighter.
References
1. Pasch MC. Nail Psoriasis: A Review of Treatment Options. Drugs. 2016;76:675-705.
2. Smith CH, Jabbar-Lopez ZK, Yiu ZZ, Bale T, Burden AD, Coates LC, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628-36.
3. Gordon KB, Blauvelt A, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2018;178(1):132-9.