A quasquicentennial reflection on psoriasis

Since the founding of the British Journal of Dermatology (BJD) in 1888, medical care has changed beyond all recognition. Dermatology is no different, but the rise of procedural dermatology has tended to overshadow the re‐emergence of medical dermatology as a distinct entity. Psoriasis is the standard bearer for medical dermatology and is an excellent exemplar of translational medicine whereby discovery has led innovation in patient care. An in‐depth understanding of psoriasis pathomechanisms has, with the introduction of biological therapies, transformed the management of patients with severe disease. Over the past 25 years the incremental gains made in our understanding of the complexities of psoriasis are a remarkable example of the crucial importance of clinician scientists and big‐team, big‐picture science. The concerted interrogation of psoriasis has yielded some of the pieces that constitute an, admittedly less than perfect, picture of the disease. To progress in any scientific discipline it is important to question prevailing dogma. Twenty‐five years ago Lionel Fry and colleagues in London did not accept the prevailing view that psoriasis was primarily a disease of epidermal keratinocyte proliferation in which inflammatory events were secondary. He promoted the now accepted paradigm of psoriasis as an immune‐mediated inflammatory disease (IMID)1 and discussed this further in his centennial review for the BJD.2 This placed psoriasis with other IMIDs including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), which although less common than psoriasis attract more publicity and more research funding. We have arrived at a point where psoriasis is accepted as a prototypic interleukin (IL)‐17 disease capable of informing the understanding and management of RA, IBD and other IMIDs. One of the main catalysts for this revolution is the enduring and mutually beneficial collaboration between the psoriasis research community and industry. Indeed, sceptics of the immune hypothesis of psoriasis were convinced of the veracity of the case by demonstration of the effectiveness of ciclosporin for the disease.3 This in turn acted as a bridgehead for other T‐cell‐targeted approaches to the disease developed by the nascent biotech industry4 and for greater involvement of immunologists in psoriasis research. Over the cusp of the millennia this had led to the development of biological therapies; those targeted at T cells, namely alefacept and efalizumab, were the first to be licensed for the treatment of psoriasis. These have now been usurped by anticytokine therapies including etanercept, infliximab, adalimumab and ustekinumab. The pipeline of new systemic therapies for psoriasis is vibrant with the likelihood that as many as three anti‐IL‐17 biologics5 6 7 will be licensed for the treatment of psoriasis within the next 5 years, in addition to orally delivered small molecules targeting Janus kinases8 and phosphodiesterase.9 Other cytokine‐targeted biologics and small molecules are in phase 2 and 3 trials for severe psoriasis. The effectiveness of the new biological therapies has raised expectations that the current gold‐standard outcome of 75% improvement in Psoriasis Area and Severity Index (PASI 75) will, I predict, be replaced by PASI 90. This begs the question: if these new treatments are so good where then is the unmet need in the management of psoriasis? Only a small percentage (around 5–10%) of patients with psoriasis have disease of sufficient extent to classify as ‘severe’ and be suitable for biological therapy. Thus, the vast majority of patients with psoriasis have either mild (60%) or moderate disease (30%). Mild or limited‐extent disease is managed with topical therapies. There is an unmet need for topical therapies that are more cosmetically acceptable and applied at a lower frequency (e.g. thrice weekly) than those available currently, thereby enhancing medication adherence. Patients with moderate psoriasis are defined as having disease that is too extensive for topical therapy alone but not severe enough to be eligible for biological therapy. There have been no recent additions to the therapeutic armamentarium for this group. If the small molecules, or indeed the new biosimilars, could be trialled in this group of patients with moderate disease and were found to be effective, safe and economical, this would be of significant benefit for an underserved group.